First Annual Progressive MS Day – Wednesday, March 28, 2018

Okay, all of my fellow progressive MSers, we finally have a day to call our own! This Wednesday, March 28, 2018, will be the first ever Progressive MS Day, a time to draw the world’s attention to this most debilitating form of the scourge that is multiple sclerosis.

As most of you already know, the majority of MSers (approximately 85%) are stricken with the relapsing-remitting form of the disease (RRMS) which is, of course, no picnic itself. Despite the advent of immunosuppressive drugs that effectively reduce relapse rates and the formation of new lesions in relapsing patients – medicines that carry with them laundry lists of serious and potentially fatal side effects – many of these patients may eventually transition to a progressive form of the disease, known as secondary progressive MS (SPMS). This stage of the disease sees patients no longer experiencing relapses and remissions, but instead a slow and steady decline in physical and mental functioning. Though there are currently over a dozen drugs approved to treat RRMS, there is only one approved to treat SPMS.

A minority of MSers (about 10%-15%) start off with progressive disease. This form of the disease is known as primary progressive MS (PPMS) and is considered the most challenging type of MS to treat. Currently, there is only one approved drug for the treatment of PPMS, and its effect on this debilitating monster is relatively modest, slowing down the progression of disability by about 25% in some patients.

Given this backdrop, it’s high time that the public is made aware of the ugly side of MS, the side which doesn’t have patients Dancing with the Stars or climbing Mount Everest. Progressive MS Day will offer our community a chance to draw attention to this particularly daunting form of MS, and by doing so hopefully draw resources towards treating and ultimately conquering it. Several states are expected to officially recognize Progressive MS Day, along with most MS patient advocacy groups. It is expected that this first Annual Progressive MS Day will grow in scope in years to come, but this year the event will be staged primarily in the virtual world of the Internet. Baby steps, folks, for those of us who can take any steps at all.

Progressive MS Day has been kick-started by the drug company Genentech, which manufactures and markets Ocrevus, the only drug currently approved by the FDA for the treatment of progressive MS. Yes, it’s not like me to do any promotion on behalf of the drug companies, and I have written several lengthy articles on Ocrevus and the issues surrounding it (click here and here). But, just like politics, crippling diseases can make for strange bedfellows, and the idea of a Progressive MS Day seems pretty good to me regardless of where it was conceived. As patients and their loved ones struggling with this illness, let’s take hold of this day and make it our own.

So, what can you do to help spread the word? Well, you can start by using the fancy-schmancy Progressive MS Day Facebook frame on your Facebook profile picture. I must admit, being an avowed Facebook hater, I had no idea what a Facebook frame was, but I just managed to add it to my profile pic and I think it’s quite nifty indeed. Please follow the instructions on the below graphic to add the frame to your own profile pic, and it’ll be like we have all revealed ourselves to be members of one of the least influential secret societies on the planet.

In addition, please use the hashtag #ProgressiveMSDay on your social media posts regarding the event. That way, nefarious groups like the Russian intelligence services and Cambridge Analytica will be able to forever tag you as a person with a crippling illness.

Just to add my own Wheelchair Kamikaze twist to the day, I am requiring, with absolutely no exceptions, that everybody who reads this post compose a Progressive MS haiku and post it in the comments section of this blog or on my Facebook page, if that’s how you reached this blog post. If you cheat and don’t compose a haiku, I swear I will hunt you down, sneak up on you, and when you least expect it shout “Boogie Boogie Boogie” at you. Believe me, writing a Progressive MS Haiku is much more pleasant than having a surprise “Boogie Boogie Boogie” shouted at you. If you don’t believe me, just click on the video below:





For those who have forgotten the rules of writing a haiku, let me refresh your memory. Haiku is a Japanese form of poetry, composed of only three lines. The first line must be five syllables, the second seven syllables, and the final third line 5 syllables again. Easy peasy haiku squeezy. As luck would have it, “Progressive MS” is five syllables and therefore makes for an easy first or third line.

To get you started, here are a few Progressive MS haikus I composed myself. Please use the hashtag #ProgressiveMSHaiku if you post your own poetic creations on Facebook, Instagram, or Twitter.

Haiku #1
Progressive MS
Stole everything but my soul
You mother f*cker


Haiku #2
Progressive MS
Enough with the half-assed drugs
I want a damned cure


Haiku #3
Progressive MS
Stick my head in a blender
And please press purée


Haiku #4
Stripped of all pretense
I discovered my essence
Progressive MS

Right then, I’m sure you get the idea. Now let’s have at it…

15 Years a Progressive MSer

You think back and it seems like a million years ago, or yesterday. The first Sunday of March 2003, an unusually cold day for that time of year. Despite the winter chill, you decide to take your beloved Labrador Retriever, Stella, for a long walk along the Hudson. After strolling about 2 miles on the paved path running next to the river, you turn homeward. You don’t return the same way you came but instead choose to take the city streets back to your wife, waiting in your apartment.

On the way home, you slowly notice that your right knee is buckling backward, causing a peculiar limp. It’s not painful as if with a sprain or bruise, but instead, a weird hitch that seems caused by weakness within the knee itself. As you walk further the limp becomes more pronounced, and the inside of your head starts feeling kind of fuzzy. It’s all very strange and unsettling. You know in your gut this isn't normal, that something fundamental has changed.

About two months later, after a disconcerting blur of doctor’s appointments and medical tests, you’re given a preliminary diagnosis of multiple sclerosis. It’s one week before your first wedding anniversary. You’re sad and disoriented and angry and frightened, very frightened. Though you’re still mostly ignorant about the disease itself, you instinctively know you've reached an unhappy line of demarcation. There will now be a time before the limp and after. Little do you suspect how stark a marker this will become, a deep impenetrable moat separating two entirely different lives, both lived in one lifetime.

Now, 15 years later, your old healthy life is receding faster and faster into the haze, like a dream remembered crisply upon awakening but lost to the ether by noon. After the limp appeared the disease hit fast and hard. No relapses and remissions for you, only progressing disability, a creeping paralysis. Less than four years after that cold day in March, the beast forced you to "retire" at the ripe old age of 43, just when your career was poised to go parabolic. A year later MS planted your ass firmly in a wheelchair. Fast forward 10 years to the present and your right side is dead weight. Your declining left side insists on following the same horrid script written by your right, like a bad sequel to a terrible movie. Somehow, on most days you outwit despair, focusing on whatever glimmers of hope the gaping abyss before you can’t hide. On other days the darkness wins out.

You remember that years before the limp you'd experienced a series of odd symptoms that defied explanation. In 1997 the doctors thought you might have a rare form of lupus, but the medical minds could never arrive at a conclusion, and during the five or six relatively quiet years after you pushed any concerns aside. On the whole, that would make it 21 years since things started going haywire. Your disease could be getting its bachelor’s degree by now. A BS in MS, or, more appropriately, a BS in BS. As an adult, you've been sick longer than you've been healthy. The gods must be crazy, and an indifferent universe could not care less.

You ponder all the things these wearisome years have taught you, from nuggets of wisdom to knowledge you’d rather not possess. You’d have been perfectly happy to live out your days not knowing that for some reason you quickly fall asleep in the noisy, claustrophobic confines of MRI machines, that you’d rather have a spinal tap than dental work, and that you have an innate ability to grasp complicated medical concepts and translate them into plain English. As hidden talents go, you have been fine with leaving that one undiscovered.

Then again, you always had a knack for cutting through the bullshit, and the reality is that most medical jargon exists primarily to confuse the public and hide the fact that large parts of the purportedly gleaming modern medical miracle machine are in reality constructed of chewing gum and chicken wire. You would relish being happily unaware of the fact that for some physicians medicine is indeed a calling, but for many others it is primarily a business. Just like any other job, some are very good at practicing medicine, but others just plain suck. What do you call somebody who graduates from medical school with a C- average? A doctor.

All the downtime that comes with being a cripple has provided you ample opportunity to dissect your long-lost healthy life and graced you with perspectives you likely would have otherwise never gleaned. You remember with deep regret all of the healthy time wasted on the small stuff, and you now see with crystal clarity that almost all of it was small stuff. If you could only have back half of the sleepless nights and anxiety-filled days vainly spent lamenting lost loves and missed opportunities. In retrospect, you see that new romances and promising circumstances inevitably came your way just as soon as you reluctantly let go of your negativity and allowed room for new people, places, and things. Our emotions are born of us, not we of them, and just as you now most often choose hope over despair, you could then have decided to seek contentment rather than wallow in self-imposed neurotic torment. Over the long run, most people are dealt an equal number of good and bad hands; it’s the way you choose to play them that determine the winners and losers. But just as youth is wasted on the young, health is wasted on the healthy.

You think of all the incredible souls you’ve met since your diagnosis, other MSers coping with the disease with their own mixture of poise and grit in the face of mounting indignities and physical insults. They have inspired you, commiserated with you, laughed and cried with you. You rue the toll you’ve seen the monster take on so many. You grieve for those who gave it their all but eventually succumbed. You remember each of them with perpetual sadness at their passing and mounting anger that more has not been done to put an end to this scourge. Treating but not curing is a great business model, but far too many human beings are left withering on the vine as the MS industry seems quite content with this paradigm, it's coffers overflowing.

The ripple effect of the disease is insidious, and you feel guilt at the impact your illness has had on your friends and loved ones. You are keenly aware of the palpable emotional pain felt by your old mom and dad when they see or hear about your ever compounding struggles, of the hidden disappointments experienced by your incredibly loyal wife who has watched her own dreams of a future filled with romance and adventure pilfered and plundered, of the unreturned emails and phone calls from friends left wondering why you choose to remain out of touch even though you hardly leave your apartment. You have no real answers for them, except that on some basic level you now understand why gravely wounded animals retreat into the brush to meet their fates alone.

Most 15 year anniversaries warrant some sort of celebration, but you don’t feel much like celebrating this one. You are grateful to still be here and to retain the functionality to write this essay, but having been struck with this disease is something you will never, ever get used to. Each day you awake to the shock that your dreams are not reality and your reality is not some demented dream. In instants without distraction, you wonder how much more of this you can take and even how much more of this you want to take? 

You somehow find ways to occupy yourself despite a growing alienation from the healthy world that surrounds you. You fight the envy you feel for those who walk and jog and gesticulate, utterly oblivious to their incredible good fortune at simply being able to do so. You listen to those tied in knots by troubles that you now realize are mere fripperies, and fight the urge to scream that you’d swap their plight for yours in half a heartbeat. You are not proud of these feelings, but there they are.

Most of all, you simply persevere. You try to make sense of it all, to tease some meaning from these last 15 years, to convince yourself that there is some method to this madness. You wonder if some long-ago actions taken or not taken, or decisions made or not made, might have led you down a path free from MS. You mourn what might have been, what almost was. You dig for nuggets of hope and reasons to believe, even if that means mining through vast mounds of existential detritus. 

Time and time again you ask yourself and the universe, “what’s the point?”, until you finally realize that the real question is “what’s the point of asking what’s the point?” You decide that if there are any answers, they are beyond the scope of your comprehension, and then you turn on the latest episode of The Walking Dead and start asking the really important questions, like how in the world you would charge your electric wheelchair during a zombie apocalypse? And, if you were to become a zombie, would you suddenly be able to walk? Or would you be one of The Rolling Dead?

Priorities, friends, priorities…

Here’s one of my favorite songs by the great American songwriter John Prine, the lyrics of which pretty much sum it all up for so many, sick and healthy alike. BTW, an “Angel from Montgomery” is what death row inmates used to call a governor’s stay of execution in the state of Alabama…

Tisch Center MS Stem Cell Study: Interview with Dr. Saud Sadiq, Director and Lead Research Scientist (Part One)

The Tisch Multiple Sclerosis Research Center of New York (click here) recently published the Phase 1 results of the first-ever FDA approved multiple sclerosis regenerative stem cell study (click here). The results created quite a buzz in the MS community, as the headline results stated that 70% of trial participants experienced increased muscle strength, and 50% saw improved bladder function. As the study included only patients with progressive MS, many of them with advanced disability, these results seem especially impressive.

Given the level of interest in this trial and stem cells in general, I thought it important to interview the man behind the study, Dr. Saud Sadiq, the Director and Lead Research Scientist of the Tisch MS Research Center. Luckily, Dr. Sadiq has been my MS neuro for the last 14 years, so a simple phone call was all that was needed to set things up. Dr. Sadiq and his researchers had been working towards this Phase 1 study for over a decade. Since the Tisch Center is not affiliated with any academic or healthcare institution, all monies for the trial were raised privately through a certified nonprofit foundation.

My interview with Dr. Sadiq is quite long but full of important information, so I’ll publish it in two parts. This installment will explore the recently released Phase 1 trial results and their potential implications. The next installment will include an overview of the upcoming FDA approved Phase 2 trial, as well as a discussion of how regenerative stem cells might work and their possible impact on the treatment landscape of multiple sclerosis. It also covers some of the many different areas of groundbreaking research currently underway at the Tisch Center's laboratories. I’ll publish the second installment next week.

This interview was lightly edited for readability. I’ve included some “WK Notes”, which explain in layman’s terms some of the more complicated medical jargon used in the discussion.

WK: Dr. Sadiq, you recently published the results of your Phase I MS stem cell trial, and they look quite strong. To start, can you tell me about the patient population of the study?

Dr. Sadiq: The patient population consisted of patients with clinically definite multiple sclerosis who had either secondary progressive or primary progressive MS. They had relatively stable disability scores – we use the EDSS scale to assess disability scores – in the years preceding inclusion into the study. Their EDSS needed to have not changed in the six months proceeded the study. Of the 20 people in the study, 10 of the patients we included used wheelchairs or had EDSS of 7.0 or above, and another 10 patients had an EDSS of between 3.5 and 6.5. The majority of patients were in the more disabled category and were using aids such as canes or wheelchairs.

WK: Why didn’t the study include any relapsing-remitting patients?

Dr. Sadiq: Well, remember, this was a Phase 1 trial that was designed primarily to assess safety. Relapsing-remitting patients tend to do well with disease modifying treatments, so evaluating recovery would have been much more difficult, even though this wasn’t a primary focus of this trial.

WK: You mentioned disease modifying drugs. Were the patients chosen for the study on disease modifying drugs, and if so, did they continue them throughout the study?

Dr. Sadiq: Yes, most of the trial subjects were on the drugs we commonly use to treat MS, including Tysabri, Rituxan, and intrathecal methotrexate (WK note: intrathecal (spinal) injections of methotrexate is one of Dr. Sadiq’s preferred treatments for patients with progressive MS. He also treats many of his progressive MS patients with Rituxan).

WK: What was the age range of the patients?

Dr. Sadiq: The youngest patient was in his 20s, and the oldest were in their 60s.

WK: Let’s talk about the type of cells that were used. These were not raw mesenchymal stem cells, which are the most common type of cells used in other stem cell trials and in for-profit clinics, correct?

Dr. Sadiq: That’s right. Basically, in our laboratory, we take a patient’s bone marrow and separate out the mesenchymal stem cells. We then purify and clone them, and then freeze them for use in subsequent treatments. The cells harvested from one bone marrow extraction – we harvest from the breastbone – can be used for multiple procedures. Before the actual treatment, the cells are then grown to about 100 million mesenchymal stem cells which we then convert into neural progenitor cells, cells which are committed to a neural lineage (WK note: neural progenitor cells are stem cells specific to the central nervous system). We usually get between 5 million and 10 million neural progenitors, and that’s what we inject into the spinal fluid of the patients.

WK: What exactly are neural progenitor cells as compared to raw mesenchymal stem cells?

Dr. Sadiq: Mesenchymal stem cells have the ability to differentiate into several different types of tissues. They can turn into fat cells or cartilage cells, but they can also differentiate into heart cells and liver cells, among others. Because we were injecting cells directly into the spinal fluid, we wanted to commit them to neural lineage so they would not differentiate into other kinds of tissues once inside the patient.

WK: I understand that the transformation process that turns mesenchymal stem cells into neural progenitors is something that was developed exclusively in the Tisch Center’s laboratories?

Dr. Sadiq: Yes, we published the process in a number of papers. The details of the differentiation process were detailed in these reports.

WK: So, the details of this process aren’t a secret, they can be replicated in any stem cell laboratory?

Dr. Sadiq: Yes, between this paper and previously published papers all of the details are available.

WK: To your knowledge, though, the Tisch laboratories are the only ones using this process?

Dr. Sadiq: Yes.

WK: Let’s talk about the treatment protocol that was used in this Phase 1 trial. How many stem cell treatments did the trial subjects get, and at what time intervals?

Dr. Sadiq: In this Phase 1 trial, we used three treatments on each patient, and the treatments were given every three months. We used between five and 10 million cells for each treatment. So, in this trial of 20 patients, we did a total of 60 stem cell treatments, and roughly 80% of those involved the injection of 10 million neural progenitor cells.

WK: How long did the study last? And was there a placebo control group?

Dr. Sadiq: The trial lasted two years, and there was no placebo control group. The capacity of our laboratories at the time was a limiting factor, so we had to stagger the treatment of patients.

WK: Even though the trial lasted two years, none of the patients received more than three treatments, and they all received them at three-month intervals, correct?

Dr. Sadiq: That’s right, nobody got more than three treatments.

WK: Okay, let’s move on to the topic that’s probably of most interest to patients, the actual results that you saw from the trial. The headlines were that 70% of the patients are an increase in muscle strength and that 50% saw improvement in bladder function. Could you give us some details on those numbers?

Dr. Sadiq: I think the main thing that has to be stressed is that the study was designed to look at safety and tolerability because nobody in a trial setting had previously injected stem cells multiple times at regular intervals into patients. We really had to establish safety and tolerability. We did this successfully, as all patients received all of their treatments and tolerated them well. There were no adverse effects except for very mild headaches and fever, which were transient and generally didn’t last more than 24 hours. There were no hospitalizations and no deaths, and this safety profile was really the primary purpose of this Phase 1 study.

As to the question of efficacy, we have to be very careful because this was not a placebo-controlled or blinded study, and most of the patients expected that they would get better. What we did see when assessed by muscle exam using the standard assessment tools – which were performed by a neurologist who wasn’t involved in the administration of the cells – was that 70% of the treated patients did see an increase in muscle strength in at least one muscle group. In addition, 50% of patients had significant bladder function improvement.

WK: Did some patient groups appear to respond better than others?

Dr. Sadiq: Yes, although patients did tend to improve across the board. Not unexpectedly, the less disabled they were, the more likely they were to improve. Overall, the less disabled did better than those with higher degrees of disability. Also, the secondary progressive patients tended to do better than the primary progressive patients. But remember, these were very small numbers, only a total of 20 patients of which only four had PPMS. But generally, we saw a drop off in response rates in patients with EDSS 6.5 and above.

WK: Why do you think there was this drop-off in efficacy seen in patients with EDSS 6.5 and above?

Dr. Sadiq: I think the integrity of axons is probably a key factor in whether they will rehabilitate or not. If you still have an electrical connection, it’s easier to repair, and scar formation from lesions probably also impedes repair. The less structural damage there is, the easier it is to repair the problem.

WK: What are your thoughts on repairing the damage of patients with higher levels of disability, who currently must rely on wheelchairs?

Dr. Sadiq: I think these are our hardest challenges. Once we can figure out how to eliminate scar tissue in the central nervous system, that will really open the door (WK note: scar tissue is created by the damage done by long-standing MS lesions). At one point we were using enzymes to try to eliminate scars. Once we can understand not just remyelination but also the regeneration of axons, I think that will be the way to achieve the goal of restoring function in more disabled patients (WK Note: axons are the long threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells). That’s why we are so focused in our lab in trying to figure out primary progressive multiple sclerosis.

WK: Were any of the patients complete nonresponders?

Dr. Sadiq: Yes, there were. Some of the PPMS patients as well as some of the more disabled SPMS patients.

WK: You mentioned the lack of a placebo-controlled group. I’d like for a minute to discuss the placebo effect because many patients don’t, I think, have a very good understanding of what the placebo effect actually entails. Many believe that when improvements are attributed to the placebo effect that these benefits are being disparaged as imaginary or “made up” by the patient. Could you comment on the science behind the placebo effect?

Dr. Sadiq: The placebo effect is real. It’s scientifically shown to be real. Even in cancer trials, whatever the mechanism, it’s real. It’s not simply psychological. It’s a conviction where the patient thinks they are going to get better and somehow that has a physical impact. Now whether the brain produces certain well-being cytokines or humoral factors or if you get an endocrine surge, somehow that has a positive effect that we still don’t fully understand. Since the late 1950s, the placebo effect has been recognized as a genuine phenomenon. In fact, there is a case of a cancer patient who got cured even though they had been given a placebo and not the drug being tested. So it’s not just some insignificant, mild effect. Generally, it’s considered that in any study without a placebo arm there’s about a 30% effect that can be attributed to placebo. This is real, when the patient is hopeful, the patient often feels better.

The thing about our study which is encouraging and leads me to believe the improvements we saw are not all attributable to the placebo effect is that we saw the most improvements in the patients that were the least disabled. This is something you would expect to see in a double-blind trial. In our trial, we probably chose the worst patients to study in that they had the disease for many years and most of the patients had significant disability. Our mean EDSS was 6.8 at baseline. Our average disease duration was about 18 years. These are never the patients who are chosen for pharmaceutical company studies, who are generally much less disabled and have shorter disease duration. The patients we used actually stacked the study’s chances against getting any positive effect.

WK: Just to be clear about EDSS, what’s the difference between 6.0, 6.5, and 7.0?

Dr. Sadiq: 6.0 is somebody who needs a cane to walk, 6.5 is somebody who needs bilateral assistance like a walker or bilateral crutches, and a 7.0 is a somebody who requires a wheelchair.

WK: In the trial, what kind of results did you see in patients who were EDSS 7 or above?

Dr. Sadiq: We saw two patients who had not been able to take more than a step or two who after treatment were able to walk with a walker for 25 feet. Whether that was placebo or not, I don’t know because this level of effect hard to explain. This was out of 10 patients who needed wheelchairs. It’s certainly intriguing.

WK: So two out of ten patients who hadn’t been able to ambulate at all and were entirely reliant on wheelchairs before the trial were able to walk with the aid of a walker for 25 feet after the study, correct?

Dr. Sadiq: Yes.

WK: Well, placebo or not, that seems like a remarkable result.

Dr. Sadiq: Yes, but we need to see if similar results are seen when we do the Phase 2 trial, which will be specifically designed to assess efficacy.

I hope readers have found Part One of my interview with Dr. Sadiq useful and informative. Look for Part Two next week, in which the Phase 2 study and just how the stem cells might work are explored. We’ll also talk about some of the other research currently being conducted in the Tisch Center’s laboratories.

Ocrevus: Former Genentech Researcher Speaks Out

First, let me preface this by saying that I am not anti-Ocrevus. As I’ve stated on these pages any number of times, it is my firmly held belief that MS patient advocates who are fervently “pro” or “anti“ any MS treatment, especially to the extent that they will disparage other treatment options, are doing a disservice to themselves and anybody who listens to them. The simple fact of the matter is that there is no perfect MS treatment; each and every one has its upsides and downsides and even these are mutable depending on the particulars of any individual patient. I’m all for any treatment that offers MS patients a chance to beat back their illness relatively safely and against supposed treatments that are either completely ineffective, dangerous, or blatant rip-offs.

It's my sincere hope that Ocrevus proves to be safe and even more effective than was shown in its clinical trials. Discretion is the better part of valor, though, and it's prudent to be wary of any drug new to the market. We've seen many drugs pulled after FDA approval because of unforeseen side effects, and have also seen other drugs that in time proved more successful than was initially expected. I've written extensively on the complicated history as well as the promise of Ocrevus, which you can read by (clicking here).

During my 14 years as an MS patient, I’ve learned to be highly critical of any medical news that I read or see in nonmedical newspapers or TV shows. These outlets generally overhype any treatment or medical discovery being discussed, and are often reported by journalists who don’t have the depth of background necessary to fully question the PR put out by the drug and medical device manufacturers. I’ve oftentimes wanted to throw things at my TV set when so-called experts state “facts” that are inaccurate, deceptive, and sometimes just flat out wrong.

The mainstream press has been heralding Ocrevus as a tremendous breakthrough, practically falling all over themselves with hyperbole in describing the revolutionary nature of this drug. The truth of the matter is that the real breakthrough came about a decade ago, when the much older drug Rituxan was first trialed on MS patients. The success of the Rituxan trials on relapsing MS shook the foundations of how multiple sclerosis was viewed by most researchers. Rituxan and Ocrevus both target immune system B cells; previous to the successful Rituxan trials, MS was generally thought to be mediated strictly by immune system T cells.

Ocrevus and Rituxan are made by the same drug company, Genentech. Even though the early-stage Rituxan relapsing MS trials were successful, Genentech chose to develop a newer molecule, now called Ocrevus, and abandon further research on Rituxan for MS. This despite the fact that Rituxan had a long record of relative safety in its original use treating non-Hodgkin’s lymphoma, and trials on Ocrevus would have to start from square one. The reasons behind this decision remain cloudy to this day, and include many that rely on absolutely legitimate scientific rationale. But, prominent among the reasons that must be considered is that Rituxan was due to come off patent in 2015, seriously limiting the profit potential of the drug.

On that note, today I came across a terrific article on the website Health News Review (click here). The piece discusses the pros and cons of the media’s coverage of Ocrevus, exploring issues such as the pharmaceutical company’s PR spin, the drug’s pricing, and the complexities surrounding its similarity to Rituxan. The article features MS neurologist and research scientist Dr. Annette M. Langer-Gould, a former employee of Genentech who worked on the development of Rituxan and Ocrevus. Her perspectives on these two drugs and on the introduction of Ocrevus are quite enlightening. Here’s an excerpt from the article, the whole of which you can and should read by (clicking here):

The Times and STAT’s piece on Ocrevus included statements from sources who hailed the drug approval, calling it a “big deal,” a “significant improvement,” “quite stunning,” and a “major therapeutic advance,” among other accolades.

But those compliments also could be applied to Rituxan, said Langer-Gould, who added that these “major therapeutic advances” actually happened more than a decade ago. But few benefited because Roche delayed Rituxan’s development and then eventually stopped it altogether. It’s misleading to paint Roche and its scientists as heroic now, she said.

“When they stopped Rituxan’s development, it was the main reason I left Genentech,” she said. “I told them ‘you’re just withholding a highly effective treatment for MS patients for another decade’–and that is exactly what happened.”

This article is so good that it speaks for itself, but I would like to add a few thoughts on a factor which hasn’t been much discussed in regards to the launch of Ocrevus. As we all should be aware by now, it’s common practice for drug companies to funnel payments directly to doctors who prescribe their drugs through the use of “consulting fees”, “honoraria, and other vehicles. According to the website Dollars For Docs (click here), Genentech, the maker of Ocrevus, leads the list of companies that engage in these practices, having doled out to doctors an eye-popping $727 million between August 2013 and December 2015. To put this in perspective, the next company on the list is on the hook for $167 million during the same period.

I’ve heard from several of my neurologist contacts that Genentech has been quite copious with its payments to MS doctors in advance of the Ocrevus launch. There is absolutely nothing illegal about this, and there is no saying how much such payments influence any individual doctor, but drug companies wouldn’t engage in these practices if they weren’t seeing a healthy return on investment. MS Neuros are among the largest recipients of pharmaceutical company monies, a fact that must be kept in mind by well-informed patients when discussing potential therapies. The Dollars for Docs website (click here) allows patients to search for any individual physician and see how much that doctor received from pharmaceutical companies during the time period mentioned above. I’d encourage all patients to take advantage of this resource by looking up their own physician to better inform themselves of what could be a motivating factor in their doctor’s decision-making practice.

If your doctor seems to have taken an inordinate amount of money from Big Pharma, don’t be shy about asking them the how’s and why’s of what you’ve learned. It’s your health that’s at stake here, and you have every right to ask as many questions as needed to make informed decisions on your course of treatment. If your doctor refuses to give you those answers, or answers in ways that leave you uncomfortable, I’d say it’s time to find a new doctor. Remember, your doctor works for you, you don’t work for your doctor.

Gee, I may just have lost a few of my neurologist friends…

Ocrevus Exclusive: Interview with Pioneering Researcher Dr. Peter Chin

Dr. Peter Chin

Late last month I was contacted via email by a representative for the pharmaceutical company Genentech, asking if I would like to interview one of the researchers who played an instrumental role in the development of the new MS disease modifying drug ocrelizumab. At first I assumed I must’ve received the email as the result of some sort of clerical error, what with my being a mere blogger and all, but I figured if they’re offering, I’m accepting.

Thus, I present the below interview with Dr. Peter Chin, the Group Medical Director of Neuroscience at Genentech. Dr. Chin has been involved with the development of ocrelizumab (tradename Ocrevus) for well over a decade, and was a pioneer in the study of the role of immune system B cells in multiple sclerosis. This line of thinking has upended much of what had previously been thought about the disease, as the working theory up until very recently was that immune system T cells were the primary culprits that should be targeted when developing drugs aimed at alleviating multiple sclerosis. Ocrelizumab is a very close cousin of rituximab, also known by its brand-name Rituxan, another Genentech product which many neuros have been using off label to treat their MS patients.

Ocrevus, an intravenous medication requiring infusions approximately every 6 months, has garnered a tremendous amount of attention of late, as it is the first drug ever to show efficacy in treating progressive MS in a late stage clinical trial and is in the process of being considered for approval for the treatment of PPMS (as well as relapsing multiple sclerosis) by the FDA. The drug has generated blaring headlines and hyperbolic chatter in the medical and mainstream press, and talking directly to Dr. Chin presented a valuable chance to cut through the clutter and get the pertinent info straight from the horse’s mouth. Not to insinuate that Dr. Chin is a horse; au contraire, he proved to be an extremely erudite gentleman during our extensive talk. He was also quite generous with his time, as our scheduled 30 minute interview lasted for nearly an hour.

The following interview is filled with a tremendous amount of important information. It’s been lightly edited for readability. I’ll publish it here without commentary and follow-up next week with my take on the potential promises and pitfalls of ocrelizumab, an intriguing new MS medication.

As you read through the interview, you’ll notice a brand-new feature on these pages called “WK notes”. These are explanations in everyday language of some of the more esoteric medical terminology that cropped up during the interview. And, if anybody’s wondering, “WK” stands for Wheelchair Kamikaze, not Wicked Kool.



WK: Dr. Chin, let me thank you for taking the time to do this interview. To start, could you explain the importance of the relatively recent research into the role of B cells in the Multiple Sclerosis disease process? I understand that when this research first started, it was not in the mainstream of general Multiple Sclerosis research.

Dr. Peter Chin: Genentech started collaborating with leading academic researchers at major universities to look into the possibility that B cells might be important in MS about 15 years ago. To some degree this was not the mainstream line of thinking, but there were researchers who had a scientific hypothesis and believed that B cells might be important because they are the cells that differentiate into cells that secrete antibodies, and antibodies are implicated in the disease pathogenesis (WK note: pathogenesis refers to the conditions that lead to the development of a disease). They are found in lesions and in the cerebral spinal fluid as oligoclonal bands (WK note: more commonly referred to as O-bands, these are one of the primary diagnostic indicators that neurologists look for when examining the spinal fluid of potential MS patients). So there was some rationale, and I think it was an exciting time when the first proof of concept studies unblinded, showing that B cells may play a more important role than anybody thought.

WK: Just to be clear, before this time it was assumed that this was a T cell mediated disease, is that right?

Dr. Chin: That’s correct. The vast majority of efforts in developing new medications up until that point were directed towards T cells.

WK: Genentech was the first to study the use of B cell therapies in MS with the drug Rituxan, whose generic name is rituximab, which was the precursor to ocrelizumab, which will be called Ocrevus if it gets FDA approval, correct?

Dr. Chin: Yes, that’s right. Genentech developed rituximab a long time ago for oncology, and we learned a lot about the medication from there. Rituximab provided a proof of concept that B cells might be important in MS, but we advanced another molecule that we believe has the best potential for long-term treatment from both the safety and efficacy standpoints for people living with MS, and that’s ocrelizumab. Ocrevus is a humanized molecule which is different from rituximab because rituximab is what we call a chimeric antibody, which has a portion of its protein sequence that is derived from mice. (WK note: a chimera is a mythical beast made up of the parts of different animals, such as a winged lion. Chimeric drugs are those that include the DNA of both humans and animals.) Ocrelizumab is a humanized molecule, meaning most of its protein sequence is human. That becomes important, particularly in a chronic disease, because ocrelizumab is hypothetically less likely to generate an immune response against the drug itself than a drug that includes more non-human DNA.

WK: Can you tell us a bit about the proof of concept studies that used rituximab to treat RRMS?

Dr. Chin: Yes, it’s important to recognize that these were small proof of concept studies, with a single dose of rituximab against placebo. It did show a reduction in MRI enhancing lesions, which was the primary endpoint, and also showed about a 50% reduction in relapses against placebo, in a six-month period. So it did provide some preliminary information that targeting CD20 positive B cells might be effective (WK note: CD20 is a protein that appears on the surface of a variety of different types of B cells). Around the same time, ocrelizumab was being studied in rheumatoid arthritis in a dose ranging study. One thing we looked at was multiple doses of ocrelizumab and their effects on B cells as well as efficacy and safety. We also looked at immunogenicity (WK note: immunogenicity is the ability of a substance to provoke a response in the immune system) and found that this was a molecule that had potential for chronic autoimmune conditions, and decided to advance ocrelizumab for Phase II development in RRMS, which led to the Phase III development program which was just published in the New England Journal of Medicine.

WK: PPMS trials were also done with rituximab about 10 years ago, too. Since I am suspected of having PPMS, I was tremendously interested in that particular trial. Can you talk a little bit about that trial?

Dr. Chin: The rituximab PPMS trial is a trial that I was involved in, actually, and it was a Phase II/III study of 439 patients comparing rituximab versus placebo. It was a single study, and it was a negative study. Meaning that the primary endpoint, which was the time to 12 week confirmed disability progression, was not significantly different than placebo.

WK: My understanding is that even though the trial as a whole was negative, when the data was looked at retrospectively there was a subset of patients – primarily those who were younger, less disabled, and had enhancing lesions – that did appear to gain benefit from the drug. Is that correct?

Dr. Chin: That’s right, although this finding was hypothesis generating rather than confirmatory, meaning it was not proven in the study.

WK: Okay, let’s talk about the Ocrevus MS trials, which are creating chatter all around the MS community. Starting with the RRMS studies, some of the results reported were pretty astounding. Could you describe those results?

Dr. Chin: The phase III RMS studies were called OPERA 1 and OPERA 2 (WK note: RMS refers to both RRMS and Relapsing SPMS). These were two, two-year trials – double-blind, double dummy studies – comparing ocrelizumab head-to-head to the interferon beta 1a drug Rebif. Here the relapse reductions were 46% and 47% compared to interferon. There was also a 40% reduction in confirmed disability progression, and approximately 95% reduction in gadolinium enhancing lesions compared to interferon. These are very promising results from an efficacy standpoint, and have the potential to really change the way that MS is treated.

WK: Yes, those are extremely impressive results. Were there any instances of PML, the potentially fatal brain infection that has been seen in patients taking some of the other MS disease modifying drugs, in any of the patients in the Ocrelizumab trials?

Dr. Chin: No cases of PML have been observed in any of the ocrelizumab development trials.

WK: Okay, let’s move onto the PPMS trial, which is really generating tons of buzz. Could you please summarize the studies and their findings?

Dr. Chin: The ORATORIO study is the Phase III double blinded study, lasting more than 2 and half years, comparing ocrelizumab to a true placebo. The primary result of this study indicated a 24% reduction in the risk of 12 week disability progression. Importantly, there was also a 25% reduction in the risk of 24 week disability progression, which is generally considered a more robust outcome measure for disability progression.

That 25% reduction is the reduction in risk over the entire timeframe for all the patients that were included in the trial, and that’s at least 120 weeks, but there were patients who entered the study early in the treatment period that were on the drug for a longer period of time. So the 25% reduction in the risk of disability progression is the figure for the entire cohort for the entire length of the trial.

WK: Okay, so the data from the trial tells us that this new drug for people with primary progressive MS is not reversing disability or stopping the progression of disability, but it is slowing the accrual of disability. Is that a fair assessment?

Dr. Chin: Yes, the primary result of the study is the 24% reduction in 12 week confirmed disability progression. So that is not a measure of improvement, and you’re correct, it shows a delay in the progression of disability as measured by EDSS (WK note: EDSS is a scale that measures the level of disability in MS patients).

WK: Realistically, then, PPMS patients on Ocrevus can expect that they probably will keep progressing, but it would be at a slower rate than if they were left untreated?

Dr. Chin: That’s a hard question to answer for any individual, but the overall results for the population of the study show a slowing of disability production as measured by EDSS, there is a slowing of the worsening of the timed 25 foot walk, which is another major end point in progressive MS trials. This is literally a measure of how long it takes to walk 25 foot feet. There is a slowing in the rate of brain volume loss, and, at least over the course of the trial, there appears to be a stabilization of the accumulation of T2 lesion accumulation. On this end point the placebo treated patients continue to accumulate T2 lesion volume and patients on ocrelizumab experienced a small decrease that was stable over the course of the two and half years or more.

WK: You previously noted that ocrelizumab was tested in trials for the treatment of rheumatoid arthritis. Weren’t those trials halted because of opportunistic infections and patient deaths?

Dr. Chin: There were opportunistic and serious infections observed in the Phase III program in rheumatoid arthritis. What’s important here is that rheumatoid arthritis is a different treatment paradigm. These are patients that are also on concurrent immunosuppressants in addition to ocrelizumab. (WK note: many of the rheumatoid arthritis patients in the ocrelizumab trial were taking other immune suppressing drugs in addition to ocrelizumab.)

WK: And ocrelizumab was also being trialed for treating lupus, and those trials also had to be halted for similar reasons, correct?

Dr. Chin: There were 2 studies in lupus. Ocrelizumab was studied in systemic lupus erythematosus (SLE), and that was discontinued primarily because the expectation for efficacy was low based on another study involving B cell targeting. The other study was on lupus nephritis, and there were serious infections that were observed, but the decision to halt was based on an assessment of potential benefits versus risks.

The same is true for the Rheumatoid Arthritis program. The potential for benefit/risk improvements over existing therapies, based on the data that were already on hand, was deemed not to be promising. So the studies were discontinued.

WK: Were any of these same problems – opportunistic infections and patient deaths – seen in either the RRMS or PPMS Ocrevus trials?

Dr. Chin: The ocrelizumab Phase III safety results for MS overall were very favorable. This is the data that was just published in the New England Journal of Medicine. The proportion of patients in the relapsing study with any adverse event were similar to those who were on beta interferon, and the proportion of patients with any serious adverse event, including serious infections, were also similar to interferons. The same is true with the primary progressive MS trial, which was a slightly longer trial. When compared to placebo the proportion of any adverse event, any serious adverse event, or any serious infection was comparable to placebo.

WK: In looking over the ORATORIO PPMS trial results, it appears that there were higher rates of cancer among the ocrelizumab treated population when compared to the placebo population. I believe the numbers were 2.3% of the ocrelizumab population developed cancers, while .8% of the placebo group developed cancers. Is that of any real concern?

Dr. Chin: There is a numerical imbalance in the number of cases observed, but the overall numbers are small. This is not a confirmed risk, but I will say that patient safety is important to us and we do continue to monitor this in ongoing clinical trials. We don’t believe that the totality of the data supports a causal relationship, but we will continue to monitor this in our ongoing Phase III open label extension studies. So far, in the additional data we’ve accumulated, there is no increase in the rate of cancers being seen.

WK: The earlier rituximab trials demonstrated that there was a subset of the PPMS population on which the drug appeared to be effective – primarily younger patients who were less disabled and had enhancing lesions. In the ocrelizumab PPMS study this group made up about 26% of the test subject population, whereas in the general PPMS population the number of patients displaying those characteristics is thought to be somewhere between 10%-15%. So it would appear that the ocrelizumab study was populated with a higher percentage of patients who might be high responders than are present in the real-life PPMS population. Can you comment on this possible disparity?

Dr. Chin: The first thing I would say is that the study results are designed to assess the efficacy in the entire study population. So this was not a study only of patients of a certain younger age or only of patients who had enhancing lesions or did not have enhancing lesions. I say that because when you look at subgroup results, it’s important to recognize that these studies are not designed to address the efficacy in the subgroups. Also, I would note, that in data that we presented earlier this year that there is a directional consistency, meaning that there is still a reduction in disease worsening in patients who both had enhancing lesions and did not have enhancing lesions at baseline. This was presented at the ACTRIMS meeting in February 2016.

WK: Are there differences between the mechanisms rituximab and ocrelizumab use to eradicate CD20 B cells?

Dr. Chin: There are differences in how they bind to CD20 molecules on the B cells. And there are differences in what we call effector function, and that’s the portion of the antibody that interacts with other elements of the immune system to remove the cells. So, yes, there are differences in the functions of the two molecules.

WK: The mechanism of ocrelizumab in PPMS patients that do have enhancing lesions – which indicate active inflammation within the central nervous system – would presumably be much the same as you would see in the RRMS model, in that the drug clearly reduces inflammation by targeting B cells. Can you propose a mechanism of action for ocrelizumab that would be beneficial for the vast majority patients with PPMS who don’t have signs of enhancing lesions or any other signs of active inflammation in their central nervous systems?

Dr. Chin: That’s a very challenging question, and a good question. I think what you’ve hit on is an area that the entire research community in MS is thinking about. It’s not a question that anyone can answer definitively at this point, because the mechanism of progressive MS and the evolution of progressive MS over time isn’t completely understood. I think there’s a recognition in the research community that the biology has become very complex and how intervening in one way will impact the disease is hard to predict. Genentech is a member of the Industry Forum of the International Progressive MS Alliance, a coalition of organizations that has formed to address the kinds of questions that you’re asking, so we contribute what we can to the understanding of progressive MS. But that’s a really big question that you’re asking.

I think our understanding of B cells currently, which I will acknowledge is ongoing and evolving, is that B cells do interact with T cells, and by removing B cells from circulation we may be breaking that interaction. We also know that B cells differentiate into plasma cells and plasmablasts which create antibodies, which might also be involved. (WK note: plasma cells and plasmablasts are among the more mature types of B cells circulating in the human body.) B cells also create a number of cytokines that also impact and potentially stimulate other parts of the immune system. (WK note: cytokines are chemicals secreted by cells that trigger actions in other cells.) There may be multiple ways that selectively targeting b-cells might be leading to efficacy.

WK: Just a couple of weeks ago we learned that the December 28, 2016 date for and FDA decision on the approval of ocrelizumab had been delayed until March 28, 2017. Can you shed some light on the reasons behind that postponement?

Dr. Chin: We did have an announcement about this extension of the date, and yes it’s March 28, 2017, which is the expected action date by the FDA. The FDA needs more time to review additional data that was submitted during the review, regarding the commercial manufacturing process. What I want to stress is that this is not related to the review of safety or efficacy data. It’s about the manufacturing process and the data regarding that process. This extension of the action date by the FDA is a commonly used procedural tool and they use it to allow more time to evaluate additional information. It’s not uncommon for questions that come up during the review, and as a result of those questions additional data get submitted. It’s just the nature of the process.

WK: As a final question, as a scientist who has devoted a large part of your career to studying MS and progressive MS, what do the trial results from the PPMS ocrelizumab studies indicate to you about the disease, and what can we look forward to in the future for what had previously been an untreatable and rather terrible malady?

Dr. Chin: I think the first thing I’d say is that the data that we just published in the New England Journal are really landmark data for a number of reasons. One, they highlight and confirm that B cells are important in MS, which is still a relatively new concept. That’s a major area of science that Genentech has contributed to that the entire community is continuing to work on. From a clinical trial results standpoint, this is the first molecule that has shown efficacy in both relapsing MS and primary progressive MS. It’s the first molecule under consideration for approval by the FDA for both RRMS and PPMS. It’s an exciting time and an exciting potential new medicine to be working on.

Particularly in regards to primary progressive MS, I want to make the note that Genentech is the only company that has actually done two Phase III studies on primary progressive MS. It’s something that we’ve been very committed to because of the unmet medical needs and the fact that there are no approved therapies. My great hope is that people will start to see that maybe we can do something about primary progressive MS, and build upon this first step with ocrelizumab, which is a very meaningful one.

WK: On behalf of all Wheelchair Kamikaze readers, I’d like to offer a tremendous thank you for doing this interview. On a more personal level, I’d like to thank you for devoting your career to unraveling the mystery of this dreadful disease. It’s tremendously important for a lot of people who suffer from all forms of MS, but especially those who have been without any proven treatment options for so long, who are stuck living with the misery that is progressive MS.

Dr. Chin: Thank you for that, Marc. I think it’s important for you to know that there are hundreds of people at Genentech and Roche who have worked on these primary progressive trials and the RMS trials for many years. I think I can speak for all of them that they do it with a passion for making a difference, understanding the degree of unmet need that’s out there.


I hope readers have found real value in the above interview. I’d love to hear your thoughts in the comments section.

As I stated earlier, I’ll follow this up next week with an essay on my thoughts about all things ocrelizumab, touching on many of the points that I discussed with Dr. Chin. A big thanks goes out to Genentech and Dr. Peter Chin for allowing me the chance to conduct this rather expansive interview.

Until next time…

.

Ocrelizumab Update – RRMS Trials Successful; PPMS Trial Shows Positive Effect, But Many Questions Left Unanswered

When I last posted to Wheelchair Kamikaze, I profiled the experimental MS drug Ocrelizumab, which was developed by Swiss drug giant Roche (and their US subsidiary Genentech). In press releases put out by the company two weeks ago (click here), Ocrelizumab was touted as the first MS drug shown capable of putting the brakes on Primary Progressive Multiple Sclerosis (PPMS) – a subtype of the disease which until now has been largely untreatable – as well as it being highly effective in treating the more common Relapsing Remitting Multiple Sclerosis (RRMS). These results were even more noteworthy because Ocrelizumab is the first MS drug to specifically target immune system B cells, while other currently available MS drugs (Tysabri, Gilenya) were developed to target T cells, which until now were believed by many to be the primary culprits driving the MS disease process.

Though the initial Ocrelizumab press releases were scant on details, the news certainly appeared promising, though reservations were expressed by many MS researchers based on Ocrelizumab’s development history and its close similarity with another Roche product, Rituxan, a much older drug that had gone through early trials in RRMS (very successful) and PPMS (largely a failure, but with some hints of success) back in 2005-2008. Rituxan’s development as an MS treatment was halted by Roche because of what many believe to be strictly financial concerns. Reading my previous essay (click here) will provide much background on Ocrelizumab’s development and the issues surrounding the drug.

Roche presented the details of the Ocrelizumab RRMS and PPMS trials this past weekend at the ECTRIMS conference in Barcelona, Spain. The RRMS trials were named OPERA I and OPERA II, and the PPMS trial was named ORATORIO. The results of the OPERA I and OPERA II RRMS studies were indeed impressive. These studies compared Ocrelizumab to Rebif, an interferon drug long used to treat RRMS, and found that treatment with Ocrelizumab resulted in a 50% reduction of annualized relapse rates, a 40% reduction in progression, and an 80% reduction in enhancing lesions as shown on MRI when compared to patients taking Rebif (click here – login required, but sign-up process is easy and well worth it). Adverse events were found to be similar in both groups, which is encouraging as Rebif is considered one of the safer MS medications currently available.

It should be noted, however, that the two-year length of these trials may be insufficient to detect longer-term problems that may develop as a result of the intense B cell suppression that is Ocrelizumab’s primary mechanism of action. Nevertheless, it does appear that Ocrelizumab will become a very valuable weapon in the growing arsenal of drugs used to combat RRMS, though, like all current MS drugs, it doesn’t do a thing towards actually curing the disease. But I’ll save that rant for another day…

(Please note, the following information and accompanying commentary were largely gleaned from materials contained in articles and interviews that can be accessed by clicking here, here, here, and here. I would urge all to read them for greater context and background)

Results of the ORATORIO PPMS study, while initially impressive, still remain riddled with questions. Despite the screaming headlines hailing Ocrelizumab as a “revolutionary new MS drug” by the – as usual – hyperbolic mainstream medical media (click here), the actual picture remains far more nuanced. The ORATORIO trial design was heavily influenced by the results of the failed Rituxan PPMS trial back in 2008. Though that trial was officially deemed unsuccessful, subsequent examination of the data revealed that a subset of PPMS patients in the study were seemingly helped by the drug. These patients were generally younger, had shorter disease duration, were less disabled, and had enhancing lesions on their MRIs. It’s thought that patients who fall within these parameters make up about 15% of the overall PPMS population.

It appears that in designing the ORATORIO study, Roche chose trial subjects who were most likely to benefit from Ocrelizumab treatment, specifically those who fit the demographic and disease parameters outlined above. As presented at ECTRIMS, the results of the ORATORIO study are indeed impressive, demonstrating a marked slowing of disease progression, a reduction in MS enhancing lesions, a reduction in brain volume loss, and a stable time to walk 25 feet when compared to trial subjects given a placebo. Of course, these results also mean that many of the ORATORIO trial subjects were patients with enhancing lesions (only a fraction of PPMSer’s have such lesions) and who were relatively less disabled (as evidenced by the fact that they could still walk). The majority of trial subjects also appear to have been relatively recently diagnosed, with a disease duration of approximately 3-5 years, and were under 50 years old.

Unfortunately, when Roche presented the ORATORIO results at ECTRIMS, they declined to detail the breakdown of results by patient subgroups, claiming that such subgroup analysis had not yet been satisfactorily completed. This beggars belief, as one would think that examining the data in such a way as to determine which patient groups benefited the most from treatment would be among the highest research priorities, especially given the mixed results of the previous Rituxan PPMS trials. Instead, Roche chose to give a broad overview of favorable trial results without answering some of the most important questions about those results, primary among them whether or not the patients who most benefited were those with enhancing lesions. Indeed, in the Q&A period following Roche’s presentation, presenters were questioned on just this issue by conference attendees, who were given no suitable answers other than promises that the data would be forthcoming. Roche's presentation led several experts to say the primary progressive data were less impressive than those seen with Ocrelizumab in relapsing remitting disease.

Although Roche portrayed the safety profile of Ocrelizumab in the ORATORIO trial to be excellent, they did note that there were 11 cancers detected during the ORATORIO trial on patients taking Ocrelizumab, versus only two in the placebo group.

The results of the Ocrelizumab RRMS and PPMS studies have not yet been published in any scientific journals, and it is expected that much additional data will need to be provided to publishers before the trial results will be deemed fit for publication. Getting the drug through the regulatory approval process required by government agencies such as the FDA will also necessitate a much greater detailing of trial results, including subgroup analysis which will shed light on just which patient groups were treatment responders. While it seems that the RRMS results will likely stand up to more intense scrutiny, the PPMS results may prove to be less dramatic than originally portrayed when subjected to the spotlight of journal publication and regulatory approval.

That said, even in a worst-case scenario in which only a small subgroup of PPMS patients, those with enhancing lesions,  prove to benefit from Ocrelizumab treatment, the fact that any headway at all has been made in treating PPMS is a significant step forward. If in fact the drug’s efficacy is limited to patients with enhancing lesions, and such lesions are most likely to be found in patients in the earliest stages of the disease, the importance of early diagnosis will be brought to the forefront. Given current diagnostic tools and techniques, many patients with PPMS aren’t correctly diagnosed until the disease has long since taken hold, beyond the period when enhancing lesions are likely to be present. Additionally, the fact that Ocrelizumab targets B cells should open up new avenues of investigation for MS researchers worldwide, as this potential mechanism of MS disease action has until now been largely discounted by most mainstream researchers. Perhaps these investigations might finally unravel some of the deepest mysteries of the disease, and (crossing the fingers I can still cross) eventually lead to a cure for all forms of the disease.

At this point, only time will provide us with the answers we seek. The next chapters of the Ocrelizumab saga will be getting these studies peer-reviewed and published in medical journals, a process which will shed much light on issues still in need of clarification. Roche is targeting the first quarter of 2016 for regulatory approval in both RRMS and PPMS. It will be very interesting to see whether or not Ocrelizumab is approved for the PPMS population as a whole, or, as many researchers suspect, for only a subgroup of progressive MS patients. Again, even if the latter case holds true, we will have at least made some headway in the fight against an insidious form of Multiple Sclerosis that until now has defied efforts to combat it.

At long last, it appears that the attentions of Multiple Sclerosis researchers are finally focusing on progressive MS, an area of investigation which until very recently had largely been neglected. The confounding problems represented by progressive MS will never be solved until well-funded trials are directed specifically at this disease subtype, a circumstance that finally seems to be coming to fruition. And that’s no small thing…

Attacked by a Three-Headed Beast

When I first started writing Wheelchair Kamikaze back in 2009 I had very little idea of what these pages might eventually evolve into, but I did know that I didn’t want the blog to take the form of an illness diary, a simple journal of my MS symptoms and day-to-day experiences with the disease. Instead, I wanted to concentrate more on the emotional and perceptual impact of dealing with a progressive crippling disease, of being forced to slowly watch one’s body being consumed from within while trying not to lose one’s head in the process. I also thought the blog would be a good place to share my growing obsession with digging into MS research and my efforts at making some sense out of all that I found.

Having said that, of late my physical ailments have been giving me a pretty good trouncing and I’ve started to feel as though I should probably fill everyone in on the details of my puzzling illness, especially since my increasingly feeling like crap is definitely impacting my ability to keep up with regular blogging activities, particularly so when it comes to responding to the many heartfelt comments, messages, and emails sent by the readers I value so much. I’ve always striven to be extremely open and honest on these pages, and it seems almost disingenuous for me to not directly address my physical state when feeling like crud is taking up so much of my damned time.

I’ve often referred to my condition as “complicated” or “atypical” without going into too many details or explaining exactly what I mean. So, here’s what’s been going on with me physically, in all its glory. My body seems to be under attack by a three-headed beast, a triple whammy that these days has me wondering just who the hell I’ve pissed off.

First up there’s my neurologic illness, which just keeps whacking away at me, and of which I’ve written about most often on these pages. My preferred name of this slice of my physical mess is “creeping paralysis”, which is actually an archaic moniker for multiple sclerosis and other progressive neurologic diseases from back in the 19^th century. Although I present symptomatically very much like a patient with progressive MS, many of the doctors I’ve seen have been hesitant to definitively label me as having multiple sclerosis since almost all of my test results defy the accepted diagnostic criteria for the disease.

Foremost among the odd aspects of my illness is the fact that I’ve only ever had two central nervous system lesions, neither of which have ever shown any signs of active inflammation: a tiny one in my brain and a much larger, more invasive and troublesome monster located at the very top of my cervical spine, at the critical juncture between my spine and brainstem. I’ve been told that this lesion is so invasive that it’s almost like having my head cut off.

These two lesions haven’t changed one bit or been joined by any others in the 12 years since I first exhibited the telltale limp that eventually led to my initial diagnosis, yet my physical condition has gone straight downhill ever since. In fact, this duo of destruction even show up fully formed on a set of MRIs done to get a look at my pituitary gland back in the year 2000, a full three years before I started limping. At the time these images were first made these lesions were completely overlooked, until they were discovered with much surprise by the doctors at the National Institutes Of Health while they were going over every MRI image I’d ever had done as part of a comprehensive effort to determine just what it is that ails me, a goal neither they nor any other physician has ever able to satisfactorily complete. So, I’m left with a diagnosis of “atypical PPMS”, and I’ve come to grips with this by insisting that in my case those initials stand for the “Peculiar Paralysis of Marc Stecker”.

Whatever you want to call it, my neurologic illness has been anything but kind. It’s left my right side almost completely useless, the muscles in my hand, arm, and leg withered and twisted. Most of the time my right hand is curled into an emaciated claw, an appendage that would look more at home on a mummy than on a living human being. My right side is becoming increasingly impacted as well, getting weaker and less able almost by the day. At times it seems I can just about watch the muscles in my left arm and hand melt away, and with them any remaining semblance of normalcy in my life. Throw in most of the other goodies that come with neurologic illness, such as spasticity, numbness, tingling, immense heat intolerance, and bladder and bowel issues, and the toll has been staggering.

But that’s but one tine of a three-pronged assault on my physical well-being. I also have a wide range of endocrine problems, most likely due to a severely dysfunctional pituitary gland. The pituitary is the human body’s master gland, sending out chemical signals that regulate hormone production in all of the other glands that make up the endocrine system. Because my pituitary is on the fritz – likely because of some kind of autoimmune attack – I experience a wide variety of hormonal deficiencies, some of which if left unchecked can be just as debilitating as my neurologic issues. Among other hormonal abnormalities, I suffer from low testosterone, low cortisol, and low thyroid levels. Although I take various supplements and medicines in an attempt to make up for these deficits, my endocrine system is balanced on such a razor’s edge that if anything goes awry my overall symptoms often get magnified tenfold and I’m left in a vortex of physical despair.

Lately it seems that my thyroid levels have gone completely out of whack, leaving me tremendously weak and fatigued, and overall feeling severely unwell. I’ve lost about 25 pounds in the last three or four months, most likely due to endocrine issues and hopefully not because of something more ominous. Endocrine abnormalities can often result in muscle weakness and even muscle wasting, and could account for the fevers that attack me nightly, making it difficult to figure out which symptoms are caused by my neurologic stuff and which might be attributed to my hormonal problems or some as yet undiscovered culprit.

The complicated interplay of my progressing neurologic illness and increasingly abnormal endocrine system makes me an extremely difficult to treat patient, a puzzling jumble that regularly leaves my doctors at a loss, though I give them lots of credit for working hard at trying to figure me out. I often have completely unexpected and sometimes disastrous reactions to medications, and even minor surgical procedures like biopsies or oral surgery can leave me flat on my back for weeks because my hormonal deficiencies leave my body with very little capacity to heal itself. My endocrine issues are insidious, always at work just below the surface, hiding behind and sometimes exacerbating the symptoms caused by my neurologic illness. This forces my physicians to treat me with kid gloves, always aware of the fact that my strange brew of ailments can sometimes turn typically benign treatments into nasty surprises.

The last but definitely not least of my medical challenges is the constant and often excruciating pain inflicted on me by a condition called avascular necrosis, which has attacked my shoulders and hips. Avascular necrosis (AVN, sometimes also referred to as osteonecrosis) is a disorder that causes the bones in afflicted joints to quite literally die, leading them to eventually crumble and break. Although the precise cause of AVN is not understood, the condition is known to be a very rare side effect of steroid use, and it first manifested in me about six months after I had gone through a 10 day course of IV steroids meant to curtail my rampaging neurologic symptoms back in 2006. It’s now thought that I may have been more susceptible to developing AVN because of all of my endocrine issues – the extent of which we weren’t aware of at the time – and the fact that my body was chronically deficient of the natural steroids a healthy endocrine system produces.

These days, roughly 8 years after those ill-fated steroid treatments, I’m left with the equivalent of two broken hips and two broken shoulders, and all of the attendant excruciating pain that goes along with them. I’m pretty good with words, but I’m at a loss to convey just how agonizing this condition can be. On really bad days, which of late have been occurring with increasing frequency, whenever I try to stand or otherwise put weight on my hips the bones beneath my skin can be heard loudly and horrifically popping, cracking, and crunching as they collapse into each other, sounds often accompanied by my own involuntary yelps and howls. My wife Karen often bears witness to these horrific auditory fireworks, and the look of dismay that shows on her face is heartbreaking.

Chronic, intense pain subverts every aspect of life and commands absolute attention, shackling its victims to moments of utter despair. Through the years I’ve learned at times to affect an almost dispassionate demeanor about my neurologic and endocrine problems, temporarily divorcing myself from the situation and taking on the role of observer. The ghastly pain caused by the AVN allows no such contrivances. I now fully understand why they say torture often doesn’t work during interrogations; there are moments in every day when I would readily admit to killing John F. Kennedy if it would just make the pain stop for even just a few moments.

Avascular necrosis is the leading cause of hip replacement in the United States. Unfortunately, due to my neurologic and endocrine issues I’m not a candidate for surgery as I very well might not survive the procedure, and even if I did I wouldn’t be able to do the requisite rehabilitation afterwards. For many years a powerful anti-inflammatory drug called diclofenac helped keep my pain levels tolerable, but over the last several months it has been discovered that the drug was degrading my kidney function so I was ordered to stop taking it. I’ve tried other anti-inflammatory compounds in its place, but most seem be as effective as sugar pills. I’ve been on and off of a variety of powerful painkillers, from oxycodone to Dilaudid to methadone, but even these potent narcotics don’t help all that much and I despise the way they cloud my mind. I see a very sharp and creative pain management doctor, but there’s only so much she can do. The bottom line is I must try to get through my days with two broken hips and two broken shoulders, in addition to my omnipresent and progressive neurologic and endocrine problems.

So, there you have it, my triple whammy, a triumvirate of infirmities any one of which could be absolutely incapacitating in its own right. The fact that I suffer from all three simultaneously and that they form a three-headed beast that magnifies the power of each sometimes leaves me wondering if I might have somehow been hexed, the victim of some ancient curse. I do my best not to indulge in too much self-pity and try to remain as productive as possible, even if lately that hasn’t been very productive at all. At times, though, the reality of the situation crashes through all of my defenses and leaves me shaking my head, wondering just what the hell happened.

Still, each day the sun rises anew, and as long as I’m on this side of the grass I figure I might as well get on with it as best I can. I’ve always vowed that if these things take me down they’ll take me down swinging, but with so many targets to swing at it’s hard to know precisely where to aim. Especially when taking a swing with a weakened, emaciated, and agonized arm doesn’t amount to all that formidable an attack.

I can still spit with the best of them, though, and if that’s going to be the only weapon left to me, then spit I will. Ha!
 

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On a much more uplifting note, the healthcare website Healthline.com has named Wheelchair Kamikaze one of 2015’s best MS blogs. I thank them profusely, and urge readers to click on the badge below and check out some of the other blogs that made the list. Lots of  great stuff being put out by MS bloggers these days , each with their own unique take on life with multiple sclerosis…

Healthline

Bits and Pieces: Multiple Universes Edition (includingLemtrada,theMS-Gut Connection, Progressive MS, Pharma to Doctor Payola,andmore…)

(For those receiving this via email, this post contains videos which can be viewed on the Wheelchair Kamikaze website – click here)

I’ve been reading about the very real possibility of the existence of multiple universes, a collection of hypotheses which state that our universe is actually part of a Multiverse made up of perhaps an infinite number of parallel or alternate universes (click here). As fantastical as this might sound, more and more physicists and cosmologists are coming to accept the notion that our universe is but one of many. In fact, most of the latest cosmological theories and mathematical models of existence point directly to the reality of a physical realm comprised of multitudinous universes, as well as many dimensions beyond the three which our tiny little brains can experience and comprehend.

The form that these multiple universes might take varies from theory to theory, from each universe abiding to its own unique set of physical laws and properties (and therefore some being quite bizarre and very different from our own), to a limitless number of universes similar to this one, with perhaps only subtle changes distinguishing each. The latter model supposes that there may even be an infinite number of like universes each playing out different timelines based on the boundless possible choices each of us makes on a daily basis. In other words, there could very well be universes out there where I don’t have MS, or where I finished that novel I started in 1988, or where my parents never got divorced. Of course, that would also mean that there are universes in which my parents never even met, in which case those universes would have never been graced by my presence. Such a pity.

Given the fact that I have way too much time on my hands and have been able to parse my old healthy life rather obsessively and in minute detail, picking out key instances when a different decision or action on my part might very well have resulted in an entirely different existence, maybe even one devoid of this damnable creeping paralysis, I find the idea of multiple or parallel universes extremely appealing. It gives me great pleasure to imagine a universe in which I am at this very moment driving a sleek convertible sports car way too fast down the Pacific Coast Highway. Or a universe where I would have never spent a minute watching a Tom Cruise movie (sorry, he makes my skin crawl). Or one in which my wife Karen and I just returned home from a long, leisurely walk in the park, strolling arm and arm with effortless grace and ease. How nice to think that all of these scenarios could very well be playing out as I write this, in universes coexisting with our own. Hey, the greatest minds in science say it's possible, and who am I to argue with the greatest minds in science?

Alas, here I am rooted in this universe, in which it’s time for yet another edition of Bits and Pieces, my semi regular compendium of mostly MS related news and items of interest. I hope you find this batch interesting, enjoyable, or at least tolerable, and here’s to the notion that in most other universes there’s no such thing as MS and thus no reason for some alternate version of me to write this blog or for some alternate version of you to read it.

Anyway, on with the show (I apologize in advance for the length of this post, but as I was writing it news broke that the MS drug Lemtrada had been approved by the FDA, which is a pretty big deal, so make yourself comfortable, this may be a long one)…

♦ Reversing a decision it made late last year, the FDA has approved the powerful drug Lemtrada for use in MS patients (click here). Since the drug was initially denied approval in the USA last December it was approved in over 40 other countries, including most nations in the European Union. US patients and neurologists had been agitating for its approval since last year’s FDA denial, as the drug had been shown to be remarkably effective in trials and had been used off label for some years to treat MS patients here in the USA (it was previously known as Campath). One MS neurologist I spoke to soon after the initial denial was quite upset by the FDA’s actions, telling me that the drug had not only rescued one of his patients who had been ravaged by a particularly aggressive case of relapsing remitting MS, but had actually allowed the patient to recover all the way from completely bedridden to back to work.

Lemtrada (chemical name alemtuzumab) is an intravenous drug that works by wiping out a patient’s existing immune system and then allowing it to reconstitute, presumably without the autoimmune tendencies that many believe play a major role in the MS disease process. In some respects, this is the same mechanism as HSCT, the type of stem cell therapy in which a patient’s immune system is ablated using a powerful chemotherapy regimen and then rebooted using the patient’s own bone marrow derived stem cells. It appears that Lemtrada achieves this same goal in less dramatic fashion.

Unlike all other existing MS disease modifying drugs, Lemtrada is not meant to be used indefinitely by the patients to whom it is given. Instead, the drug is administered intravenously for five consecutive days, and then again one year later for three consecutive days. Some patients may require additional infusions at some point down the line, but most do not. Trials have shown that in about 70% of patients with active RRMS the drug eliminates all signs of disease activity (relapses and new lesions) for at least three years after treatment, and in some cases for many years more. In other words, Lemtrada has been shown to put the long-term kibosh on all MS symptoms for the majority of patients with active relapsing remitting disease who have gone through the treatment protocol without further dosing, a result not seen with any other existing MS drug therapy. Some patients have even experienced a reversal of their symptoms, regaining neurological function that had been lost to the disease. As has been the case for all MS drugs so far, Lemtrada unfortunately has no apparent benefit for patients suffering from progressive MS.

These astounding results do not come without risk, however, as a majority of treated patients develop some secondary autoimmune disorders (most often autoimmune thyroid disease, which can typically be controlled with medication), and a small percentage (1%-3%) develop a very serious autoimmune blood disorder, which if caught early can be remedied before any harm is done. As might be imagined, the long term effects on MS patients by a drug this powerful are hard to predict, but the drug has been used to treat patients suffering from various blood cancers for decades. For these reasons, patients treated with Lemtrada must be monitored very closely (most likely in the form of monthly blood tests) for years after their last infusion of the drug.

In the UK, Lemtrada has been approved as a first-line therapy for patients with highly active RRMS. Here in the USA, the FDA has approved Lemtrada only as a third line drug, to be given to patients whose disease has not previously responded to two different MS therapies. This restriction may prove to be problematic, since there are indications that early treatment with the drug provides patients with the best chance for success, in the form of a complete and long-lasting remission of all MS signs and symptoms. For a full discussion of Lemtrada and its associated issues, I urge you read this article recently posted on the always informative Multiple Sclerosis Research Blog, which is maintained by neurologists at Barts and the London Medical School in the UK (click here).

Lemtrada could be a game changing drug for many RRMS patients, particularly those hardest hit by the disease, but the drug’s risk/reward scenario may prove daunting to many patients and neurologists. It will be very interesting to see how adoption of this drug plays out over the coming months and years. Will the prospect of years without any disease symptoms whatsoever tempt patients to try Lemtrada despite the drug’s potentially serious side effect profile?

Wouldn’t it be nice if researchers could come up with a highly effective MS therapy that didn’t scare the living shit out of the patients who it is supposed to help? Perhaps in an alternate universe all forms of MS can be effectively treated with hot fudge sundaes. I hope some version of me is living in that universe.

Edited To Add: a reader who has worked with this drug in her job as an oncology nurse left the following comment, which I thought valuable enough to place into the body of this post.:

As a former oncology nurse, I am familiar with Campath and this drug scares me. You can say that it has been used in treatment for blood cancer for years, but you may not know is that it is not used often and the practice I worked for stopped giving it in our usual outpatient clinic because of severe infusion reactions. There were even deaths, although that did not happen at our facility. I treated several patients with the drug and the infusion reactions were significant. The dosage and frequency of treatment is likely very different for MS, but I have seen what it can do and it is definitely a big gun that should be used very carefully.

As I previously noted, Lemtrada (the same drug as Campath) is used differently to treat MS than it was to treat cancer, but the concerns raised are certainly valid. Infusion reactions are reactions that occur while the drug is being given intravenously to a patient. Such reactions were noted in the Lemtrada MS trials, but were not deemed to be dangerous enough to prohibit the approval for the drug for use in the treatment of active relapsing remitting MS. Still, yet another variable to consider when presented with the option of using Lemtrada to treat your disease. As always, knowledge is power, and I thank Mary Beth Knapp for contributing this information.

Edited Again to Add: the folks at the Multiple Sclerosis Research Blog have posted some very interesting and valuable information on taking the risk out of Lemtrada. One of the topics discussed are infusion reactions, so this is a very pertinent and important read (click here).

♦ There has been a lot of chatter recently about the relationship between the gut and the nervous system, with evidence pointing to a direct connection between dysfunction within the digestive system and disorders of the brain and spine. One study found a relationship between a disease known as “leaky gut syndrome” and multiple sclerosis and other inflammatory diseases, at least in mice (click here). Researchers found that mice with leaky gut syndrome had higher levels of inflammatory immune cells and lower levels of immune cells that suppress inflammation, leading those mice to suffer more severely when induced to develop the mouse version of MS (on a side note, the mouse version of MS is an absolutely horrible mimic of the human disease and I usually tend to discount almost all studies that rely on it, but in this case the findings are backed up by similar observations in people).

A fascinating article in the New York Times explored the relationship between celiac disease and disorders of the nervous system (click here). Celiac disease is an autoimmune disorder of the gut triggered by the gluten proteins contained in wheat and other grains. The article details several cases in which diseases supposedly rooted in the central nervous system, like dementia and autism, were completely reversed when patients were found to have celiac disease and put on gluten-free diets. Pretty amazing stuff, which only further fuels my suspicion that many if not most MS patients (and patients suffering from other nervous system disorders) are afflicted with some as yet unidentified systemic disease rather than one confined strictly to the brain and spinal cord. Unfortunately, modern medicine has become so specialized that each physician tends to focus only at those areas of their particular expertise when examining a patient without giving enough thought to other areas of physiology that might be impacting the patient’s condition, in effect missing the forest for the trees.

Other studies have looked at the trillions of single celled organisms that populate the gut (known as the gut biome), and found that the gut biome of MS patients is often markedly different than those not suffering from the disease (click here). Normally the relationship between our bodies and the microbes that inhabit the gut is mutually beneficial. However, it seems that in patients with MS and some other immune related diseases the mix of microbes in the gut is noticeably altered. There is so much mounting evidence that links the gut biome to MS that four major US multiple sclerosis research centers have formed the MS Microbiome Consortium to further investigate the role of the microbiome in multiple sclerosis. Turns out that 80% of our immune system is contained within our gut. Who knew?

If you find all of this interesting and who would like the chance to discover just what little buggers are residing in your gut, then you’re in luck! The Human Food Project is currently running the American Gut program, which for $99 will provide a kit with which you can sample your saliva, skin, and poop (I know, yuck) to find out precisely what microbes are living on and in you (click here). The Human Food Project will do a complete DNA analysis of your samples and return a full report. The American Gut program is a crowd funded research effort, so your $99 will not only go towards purchasing your sampling kit but also help fund this ongoing project. I ran all of this info past the naturopath who works at my MS clinic before signing up, and she said that there is no guarantee that the results of this analysis will turn up anything actionable, but that you never know. At worst I’d be helping out with a valuable research initiative. Good enough for me, so I’m currently awaiting the arrival of my saliva/skin/poop testing kit. BTW, for readers residing in the UK, there is also a UK Gut program, so all you British folks can participate as well (click here).

♦ I’ve previously written about the problem of misdiagnosing MS on quite a few occasions, and here I go again. It’s estimated that between 5%-15% of patients diagnosed with MS are not actually suffering from the disease but instead from one of the dozens of other conditions that can mimic multiple sclerosis, a notion that is quite disconcerting to say the least. I myself am suffering from some strange mix of increasingly debilitating symptoms that may or may not be multiple sclerosis, so this issue is of particular interest to me. The website EmaxHealth has recently run a series of short and easily digestible articles on this subject, all of which are worth reading. The first is titled simply “Misdiagnosing Multiple Sclerosis” (click here). Other articles in this series include “Is the Diagnosis of Lupus or Multiple Sclerosis?” (click here), “Is It Multiple Sclerosis or Transverse Myelitis?” (click here), and “Is Multiple Sclerosis Mainly an Autoimmune Disease?” (click here). As I’ve also stated previously it’s easy to drive yourself nuts with this kind of information, so be careful, but if you suspect you may have been misdiagnosed these articles could be very valuable reading.

♦ Progressive multiple sclerosis is a particularly nasty form of the disease, in which patients don’t suffer from the onset of MS attacks (relapses), but instead suffer a steady neurologic decline without ever returning to their previous level of functionality. If I do have MS, it’s of the progressive type, and I’ve been forced to watch myself go from slight limp to nearly complete gimp over the last 11 ½ years without any respite or period of stability. Take it for me, this sucks. Roughly 10% of MS patients suffer from progressive disease from the outset, a form of MS called Primary Progressive (PPMS). A substantial number of people with relapsing remitting disease (RRMS) eventually transition to Secondary Progressive disease (SPMS), at which time they stop experiencing relapses and remissions and instead start accumulating ever-increasing neurologic dysfunction. Currently, there are no effective treatments for any form of progressive multiple sclerosis.

The International Progressive MS Alliance (click here) was formed in 2012 to specifically address the vexing problems posed by progressive multiple sclerosis, and to speed up research and the development of therapies aimed specifically at this form of the disease. The Alliance recently announced the funding of 22 research projects in nine countries, all aimed at helping to unravel the mysteries of progressive MS and to eventually smite this horrendous beast (click here). Let’s hope the Alliance realizes its ambitious goals sooner rather than later, as patients suffering from progressive MS have for too long been ignored by the medical research community.

They say a picture is worth 1000 words, so a video must be worth millions, and the following video put out by The International Progressive MS Alliance sums up the horrendous nature of progressive MS and the problems the disease presents to researchers better than any of my long-winded blog posts ever could. Please watch, but I’ll try to sum up the message of the video in one word: “Help!”



♦ I’ve always found it mind-boggling that pharmaceutical companies are allowed to pay off the doctors who prescribe their drugs. Of course, these actions are never quite as blatant as bald-faced bribery, and instead these payments are dressed up as speakers’ fees, trips to educational seminars, meals provided to office staff, etc. Despite this song and dance, the fact remains that many doctors receive significant amounts of money from pharmaceutical companies, and let’s face it, Big Pharma wouldn’t be doling out all that dough if they didn’t believe it was influencing the actions of the doctors receiving their “generosity”.

If you’ve ever wondered just what kinds of gifts, honorariums, and other payments your doctors may be getting from their pharmaceutical masters (oops, I mean partners), you are now in luck, at least if you live in the USA. Courtesy of the much-maligned Affordable Care Act, a new website is now online that allows patients to enter their doctors' name, click a button, and discover just what pharmaceutical company payments their physicians received in 2013 (click here). I just entered the name of one of my physicians and came up with four pages of pharmaceutical company payments to him, most for “food and beverage” expenditures. It sure is nice to know that he and his staff are well fed.

Let me be clear, I genuinely like this doctor, but the fact that pharmaceutical companies are legally allowed to engage in this kind of crap makes me want to vomit in my mouth. Perhaps if we all print out the info we get from this website and present it to our physicians, along with some pointed questions, our esteemed doctors may think twice about engaging in such activities. Whoops, there I go, crossing over into yet another parallel universe. Silly me.

♦ Okay, now that this blog post is threatening to rival the length of Webster’s Unabridged, I’ll mercifully bring it to a close. As has become my tradition (and I really do enjoy creating my own traditions) I’ll end this edition of Bits and Pieces with a music video by an artist in the “retro-soul/neo-soul” genre. This time around I present you with Sharon Jones, a sublime belter who simply oozes all of the innumerable and unquantifiable qualities that define the notions of funk and soul. This video dates back to 2007, so I guess it’s kind of old at this point, but Sharon Jones is still going strong and deserves as much attention as she can get. Though the video looks like it was made in the 1960s, trust me, it’s a product of the 21^st century, although it was shot with vintage TV cameras that its producers bought on eBay for about 50 bucks. So get ready all you cuties to shake your booties to the infectious sounds of Sharon Jones and the Dap-Kings, a righteous, mighteous, and out of sighteous infection for which I want no vaccination! Bring it on…