Monday, April 16, 2018

An Uncomfortable Truth: No $ In Cures, Says Goldman Sachs

In a development more shocking than the capture of a live Bigfoot, a recent Goldman Sachs research report (click here and here) states in black-and-white what many have long suspected: curing diseases is not a viable business model for the companies that develop and manufacture drugs. Instead, drugs that turn terrible diseases into treatable illnesses which are kept under control by the perpetual use of medicines that sustain patients but don’t cure them have become marvels of modern capitalism.

Perhaps unwittingly, the Goldman Sachs report confirms that our current medical research model is more crippled than I am. Over the past three or four decades, the interlocking mantras of “all government is bad government" and "private enterprise is the solution for everything," have led our society to hand the reins of medical research over to for-profit pharmaceutical, medical device, and biotech companies. Most of these companies are publicly traded, meaning their stock is available for trade on the world's stock markets.

The problem with this formula is that publicly traded companies are mandated by law to be beholden to their stockholders, not the end users of their products. In the case of pharmaceutical and medical device companies, these end-users are sick people, many suffering from hideous diseases like multiple sclerosis. In the cold calculus of the free-market, the job of drug company executives is NOT to produce drugs that offer the best result for the patients who take them (like, say, cures). Instead, providing the best outcome for the companies’ stockholders – in the form of ever-increasing profits and ever appreciating stock prices – is the legal responsibility of these executives.

In fact, the CEO of a drug company with an established and successful franchise of MS treatments could very well be engaged in illegal practices if they endorsed their company marketing a cure for the disease, which would destroy their existing tremendously profitable business model. In the parlance of the financial world, that executive would be in breach of his or her fiduciary responsibilities. In the parlance of the rest of the world, that executive would likely be given the heave-ho and could spend a good chunk of time in a Club Fed.

Since finding cures for diseases like MS and cancer have eluded researchers for decades if not centuries, the recent advent of medicines that treat but don't cure have been heralded as modern miracles. The lack of cures has become the accepted status quo, despite the fact that in the days before medical research was dominated by for-profit concerns, dread diseases like polio, smallpox, and tuberculosis were wiped out through the efforts of government and academic researchers. Now, though, with the science of genetic therapies rapidly advancing, the prospect – or, in the eyes of Goldman Sachs, the problem – of curing diseases is growing tremendously, threatening to upend a business model that has become incredibly profitable. To take just one example, medicines that treat but don’t cure multiple sclerosis generated over $25 billion in revenues during the last year alone.

As more and more disease-related genes are mapped and identified, the universe of illnesses that might benefit from gene therapy is expanding exponentially. Multiple sclerosis is one of those diseases, as it seems every few weeks a new set of genes are discovered that play a role in the MS disease process. The ultimate cure for MS may one day lie in altering the genes that initiate the cascade of failures that leads the body to destroy its own tissues. Ultimately, the genetic profile of individual patients may be used to tailor cures unique to their genetic makeup.

In their research report released last week, Goldman Sachs – a company that is a central pillar of our financial system with a reach far beyond Wall Street – concludes that such genetic therapies represent a vital threat to those invested in companies involved in drug and medical device development and manufacturing. In a report entitled "The Genome Revolution", Goldman Sachs analysts ask, "is curing patients a sustainable business model?" While acknowledging the vast potential of genetic treatments, the report states “Such treatments offer a very different outlook with regard to recurring revenue versus chronic therapies. While this proposition carries tremendous value for patients and society, it could represent a challenge for genome medicine developers looking for sustained cash flow." Heaven forbid! The almighty dollar must rule all, patient and societal well-being be damned.

The report goes on to make several recommendations for addressing the looming financial threat of curing rather than treating diseases, including that companies ignore rare diseases whose small patient pools would make any cures prohibitively expensive, and also that they avoid curing infectious diseases because "… curing patients also decreases the number of carriers able to transmit the virus to new patients", which would, of course, be terrible for business. The report cites the example of Gilead Sciences, which developed a cure for hepatitis C several years ago (click here), but has seen its profits plummet as the population of hepatitis C patients shrinks thanks to the success of Gilead's medication. As a result, the company’s stock value has suffered. More proof that no good deed goes unpunished.

Folks, this Goldman Sachs research paper states in black-and-white what to many has been long apparent but difficult to fathom: there is very little incentive for pharmaceutical companies to research and develop cures for diseases when marketing treatments that transform patients into customers for life is an immensely profitable business model. Those of us suffering from terrible conditions like multiple sclerosis must recognize that hoping for a cure from such entities is akin to hoping that the Easter Bunny hops into your local MS clinic and drops off a cure delicately encased in a colorfully decorated egg.

What is the solution to this situation? Well, how about putting a small tax on pharmaceutical company profits, the proceeds of which could be funneled exclusively into publicly funded medical research explicitly targeted at finding the cause and cure of currently intractable diseases. If a tax of 4% were placed on MS medications, which, as stated previously, generated $25 billion in revenues last year, a nifty $1 billion could have gone to fund independent researchers in the search for a cure for the disease. Would it place an undue hardship on MS drug manufacturers if last year’s revenues totaled $24 billion rather than $25 billion? Let’s not forget, pharmaceutical companies are granted extremely long patents on their products and don’t face much in the way of free-market competition. It’s no accident that every MS medication is priced between $60,000-$85,000, despite the fact that some of them have been on the market for more than 20 years.

Yes, I am aware that any talk of increased taxes is anathema to ideologically driven politicians and those who vote for them, but if we are to find our way out of a status quo that sees treating but not curing as perfectly acceptable, some radical changes need to be made. The current state of our medical research model has been corrupted by the siren song of blockbuster drugs, the profits from which are astronomical. As a society, we must reckon with the following question: Are profits more important than patients? Seems to me that in a country where “Life, Liberty, and The Pursuit of Happiness” are held as sacred, the answer should be self-evident. It’s tough to enjoy our inalienable rights while plagued with horrible illness. Will the incessant drive for ever-increasing economic gain dictate the future of medicine, or will we as a society finally stand up and say, “Enough!”

Sunday, March 25, 2018

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…

Sunday, March 11, 2018

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…

Wednesday, February 21, 2018

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

Dr. Sadiq and research staff at the Tisch Center
The Tisch MS Research Center of New York (click here) will soon begin its first-ever FDA approved Phase 2 regenerative stem cell study for multiple sclerosis. Last week, I published the first part of my interview with Dr. Saud Sadiq, the Director and Lead Research Scientist of The Center, which discussed  the Phase 1 study and its results (click here). As promised, here is the second part of our discussion, which focuses on the upcoming Phase 2 study, the Tisch Center's new stem cell laboratories, how stem cells might help repair damaged nervous system tissues, and some of the other multiple sclerosis research projects being conducted by Tisch Center researchers and scientists.
This interview has been lightly edited for readability, and I’ve added some “WK Notes,” which attempt to translate overly complicated medical jargon into plain English.

WK: The Tisch center is now preparing to embark on Phase 2 of your MS stem cell trial. When do you expect this next phase of the study to get started?

Dr. Sadiq: After the  Phase 1 study ended, we made a commitment at The Tisch Center that we needed to make our stem cell laboratories absolutely state-of-the-art. We’ve invested heavily in building a new stem cell lab, which is being completed now. Everything’s automated, it’s a next generation stem cell facility that will be functional and certified in about a month and a half. Then we will be prepared to start the Phase 2 study. We do still need some additional funding for Phase 2. We are applying to the National Multiple Sclerosis Society for a grant. Though they didn’t support Phase 1, given the impressive results of that trial we are hopeful that they will support us as we go forward. We also expect private contributions to help fund Phase 2, as these have always been the lifeblood of the foundation.

WK: How many patients will be involved in the Phase 2 study?

Dr. Sadiq: There will be 50 patients involved. It will be a double-blinded crossover study specifically designed to establish the effectiveness of the neural progenitor stem cells we've developed in our laboratories. So it has an entirely different aim than the Phase 1 sstudy, which was intended primarily to determine the safety and tolerability of our stem cell procedures. We are going to give Phase 2 study participants six treatments, one every two months. Therefore there will be more treatments given in greater frequency than in the Phase 1 study.

WK: So, with 50 patients, 25 will be getting actual stem cells, and 25 will be getting placebo treatments?

Dr. Sadiq: Yes, in the first year 25 subjects will get treatment and 25 will get placebo, and in the second year the ones who got placebo will get treatment and vice versa.

WK: What will the patient population look like for this Phase 2 trial?

Dr. Sadiq: The patients for this trial will have to meet much tighter inclusion criteria then the patients in Phase 1. They all must be diagnosed with SPMS or PPMS. They have to be ambulatory, so they’ll all have EDSS scores between 3 and 6.5. The FDA is requiring that we have an equal distribution of the EDSS scores. So there will be equal numbers of patients distributed between all the points along the EDSS scale. The other limitation is that all patients will need to have had the disease for 15 years or less.

WK: Will the study participants continue with their disease modifying drugs?

Dr. Sadiq: Yes, but they can’t have switched medications within six months from the start of the trial.

WK: Once they are in the trial they’ll have to remain on the same DMD for the duration of the study?

Dr. Sadiq: Yes.

WK: What will be the total duration of this trial?

Dr. Sadiq: There will be two years of study and placebo, and one year of follow-up. So a total of three years.

WK: Just to be clear, in the third year none of the patients will be receiving stem cells?

Dr. Sadiq: That’s correct, in the third year there will be no stem cells and no placebos. After the second year, all patients will have received six treatments. The patients who received stem cells in the first year will have placebo in the second year, and the patients who received placebo in the first year will receive stem cells in the second. The third year will be for observation of all patients.

WK: For all the folks out there with RRMS, if the Phase 2 trial proves successful then the stem cell protocol developed at Tisch could be applied to them as well, correct?

Dr. Sadiq: For patients with relapsing-remitting disease who experience a relapse that results in damage from which they don’t recover, stem cells could be introduced in an attempt to repair that damage. That would be the dream scenario, and it could render disability resulting from MS a thing of the past. But at this point were getting ahead of ourselves…

WK: As we move forward into a world in which stem cell treatments for MS become a standard of care, would you anticipate that patients will need continued and repeated stem cell treatments to maintain or advance whatever benefits they realize until a cure is finally found for multiple sclerosis?

Dr. Sadiq: Yes, that’s likely. I think the Phase 2 trial will really go a long way towards answering that question. It will be important to ascertain what happens to patients in the years after they receive their stem cells. Do they maintain their benefits, do they return to baseline, or do they fall somewhere in the middle? These will be significant findings. The design of this crossover trial will allow us to figure that out. My feeling going in is that patients will need stem cell treatments over the long-term, maybe not six a year after the initial treatment., but perhaps less frequently to maintain whatever improvement is seen.

WK: The neural progenitor cells developed by the Tisch Center – or any regenerative stem cells, for that matter – don’t directly address the disease process, correct? If so, does the disease remain active despite the use of these stem cells?

Dr. Sadiq: Yes, that’s right, the cells are not a cure for the disease. They hopefully secrete trophic factors that would stimulate the body’s own progenitor cells to activate and induce repair at sites of injury. (WK Note: trophic factors are elements which cause the body to maintain or start some action, in this case repairing damaged nerve cells and possibly affording some protection against attack from immune cells.)

WK: So, the stem cells may not necessarily repair injury all by themselves, but they may jumpstart natural repair mechanisms within the bodies of the patients in which they are implanted?

Dr. Sadiq: I think that’s the most likely mechanism. Whether they play some direct role is something we have to figure out, but I think it’s more likely that they’ll turn on a patient’s own progenitors and also create a trophic environment that acts as a shield from the immune system and allows the body to make repairs.

WK: I know that stem cells aren't the only focus of the Tisch Center's researchers and scientists. I’d like to touch on The Tisch Multiple Sclerosis Research Center of New York itself, and some of the other areas of research that are currently ongoing in The Center’s labs. Could you give us a peek inside and tell us about some of the other projects Tisch researchers are working on?

Dr. Sadiq: Well, at the Tisch Center our original goal was to identify the root cause of the disease. It may be some type of immune cell, or some unidentified infectious agent, or maybe some other environmental element. Once we can identify the cause of multiple sclerosis, we can then methodically work towards a cure. And finding a cure is our ultimate goal.

WK: So, the Tisch Center currently has researchers who spend their days searching for the root cause of multiple sclerosis?

Dr. Sadiq: Yes, absolutely. I try to focus on the real challenges that I see as a clinician treating patients every day. My focus is on trying to understand primary progressive MS, which is perhaps the most challenging form of MS as far as treatment is concerned. There are very few treatments that can alter the course of progressive MS. We’ve created an animal model in our lab to try to understand the mechanisms of progression and why remyelination does not take place at all in this form of the disease. In relapsing-remitting MS we see damage occur and then some repairs get made by the body, especially in early disease. This is something not seen in progressive MS. We need to understand the mechanisms of progression better. We are also focused on cognition dysfunction because that can really dehumanize the patients who suffer from severe cognitive deficits.

We are also hard at work identifying biomarkers that can indicate the activity and severity of the disease. We’ve published a lot of papers in this area. We are doing a lot of work on metabolic dysfunction in the central nervous system in MS, and hopefully, that will lead us to readily identify markers that can pinpoint progression and disease activity, which will, in turn, allow us to assess the effectiveness of treatments in individual patients. In conjunction to the Phase 2 stem cell study itself, one of our aims is to analyze the spinal fluid of all of the study participants for markers that may predict which patients are going to get better by Identifying which patients experience actual repair and remyelination. The goal of identifying biomarkers is to be able to tailor treatments to each individual patient, specific to them and the intricacies of their disease. MS is a very heterogeneous illness, meaning that it affects each patient differently. Through the use of biomarkers, we hope to be able to address these differences on a patient by patient basis.

WK: The Tisch Center is not affiliated with any hospital or academic institution, correct, so it’s an entirely independent research entity?

Dr. Sadiq: Yes we are completely independent. We run Tisch like an academic center in every regard. We have guest speakers and all of the activities that would be associated with typical University research centers, but we are not affiliated with any academic centers. We retain absolute independence in choosing our areas of research.

WK: If you don’t have any of these affiliations, how is all of the research we’ve discussed funded?

Dr. Sadiq: We rely entirely on grants and donations. We use almost all the funds raised directly for research. Fully 90% of all monies raised goes directly into research, which is really an extraordinarily high number compared to other organizations. We keep expenses very low, so only a small percentage of funds raised go towards administrative costs and other such overhead. All of our tax forms and documentation in this regard are available online.

WK: My understanding is that you are not currently receiving any funding at all from the National Multiple Sclerosis Society. Is this correct?

Dr. Sadiq: Yes, that's right, we’ve had some bad luck with the MS Society, but they promised to look into our Phase 2 study, and I’m putting in a grant application. Hopefully, this time they’ll get involved.

WK: Obviously, the Tisch family (click here) is involved, but where does the rest of the Center’s funding generally come from?

Dr. Sadiq: The Tisch family is a very big supporter, but so are our patients and their loved ones. We have a very loyal following of patients and their families and other supporters that really enable this to happen. They’ve been supporting us for close to two decades, even before we were formed as an independent center.

WK: How much is this Phase 2 trial going to cost?

Dr. Sadiq: The build-out of the laboratory cost $5 million, and that’s a done deal. The trial itself calls for another $4 million, and we are currently raising funds for the study itself.

WK: So funding is still needed for the Phase 2 trial?

Dr. Sadiq: Yes.

WK: Well, speaking strictly for myself as a patient who has been ravaged by this disease, I can’t think of any cause more important and worthy of donations.

Dr. Sadiq: That’s very kind. Maybe I should hire you as a fundraiser…

WK: You can pay me in stem cells… Even though I know I don’t qualify for the trial because of my  level of disability…

Dr. Sadiq: That’s true, but don’t ever lose hope. Every day researchers here at Tisch and others around the world are working hard towards solving the puzzle of MS. I’m personally obsessed with curing multiple sclerosis.

As a patient of Dr. Sadiq’s, I can attest to his obsession with curing the disease. The man works at least six out of every seven days and even has a bedroom behind his office at the clinic affiliated with the Tisch Center. The clinic is called The International Multiple Sclerosis Management Practice (click here).  I’m also acquainted with some of the researchers at the Tisch Center, who are so dedicated that they'll even put up with my incessant questions when I manage to corner one of them with my wheelchair.

For those interested in donating to the Tisch Center, you can learn about the various ways to contribute by (clicking here). If you’d like to encourage the National Multiple Sclerosis Society to get behind the first ever FDA approved Phase 2 MS stem cell trial with a nice big grant, here’s a webpage with contact info for all of the Society’s senior leadership (click here). Please be polite If you do reach out to the NMSS. As my grandmother always told me, you can catch more flies with honey than you can with vinegar…

Wednesday, February 14, 2018

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.

Monday, February 5, 2018

Can A 100-Year-Old TB Vaccine Stop MS, Diabetes, and Other Diseases?

If I told you that a century-old vaccine – initially developed to combat tuberculosis – now appears capable of stopping or slowing multiple sclerosis, type I diabetes, and other autoimmune diseases by changing the workings of the immune system at the genetic level, would you think I’ve finally gone off the deep end? Well, hold onto your hats, or hair, or whatever else may be sitting on top of your head because the truth is out there (yes, I’ve been binge-watching episodes of The X-Files), the ramifications of which could change the treatment landscape for many hideous diseases.

I recently attended a presentation given to a group of neurologists and MS researchers by Dr. Denise Faustman (click here), a Harvard University medical researcher. Dr. Faustman is at the forefront of research into the Bacillus Calmette-Guerin (BCG) vaccine and in early trials has shown that the vaccine is capable of restoring dysfunctional parts of the immune system in patients with long-standing type I diabetes (click here). Dr. Faustman is currently conducting a phase 2 trial on long-term type I diabetics, with hopes of reporting results this summer.

Other studies have shown that BCG can alter the course and severity of multiple sclerosis (click here), and ongoing studies around the world indicate that the vaccine could have similar effects on a wide range of autoimmune diseases (click here), including Sjogren’s disease, fibromyalgia (click here), and immune mediated allergies. The vaccine is also the preferred treatment for a common type of bladder cancer (click here) and there are indications that BCG may dramatically reduce the incidence of leukemia in children (click here). It is even effective as a treatment for leprosy (click here)!

The BCG vaccine was developed at the beginning of the 20th century by two French scientists, Albert Calmette and Camille Guerin, work for which they were nominated for the Nobel Prize in 1928 (click here). Spurred in part by the observation that milkmaids appeared to develop tuberculosis in far lesser numbers than the general population, the two scientists developed the BCG vaccine using live but very weakened bovine (cow) tuberculosis bacteria, which makes cows sick but isn’t infectious in humans. The vaccine was first used in 1921 and although it ultimately proved to be only 20%-50% effective its use soon became widespread. It remains the only vaccine for TB and is still used extensively throughout Third World countries where TB runs rampant. The BCG vaccine is on the World Health Organization’s List of Essential Medicines.

At that time of the vaccine’s development, tuberculosis was epidemic and deadly. In the 1800s, TB caused about 25% of all deaths in Europe (click here). The disease, commonly called “consumption” back in the day, is highly contagious and has been infecting mankind since antiquity. Signs of TB have been found in human skeletal remains dating back millennia, even into prehistory. Before the Industrial Revolution and the beginnings of modern medicine, folklore had it that tuberculosis was caused by vampires. My recent X-Files binge tells me not to completely discount this theory.

BCG effect on MS
(click to enlarge)
Fast-forward to the 21st century, and modern scientists are discovering that the potential uses of the BCG vaccine go far beyond the treatment of TB. A phase 1 trial conducted by Harvard’s Dr. Denise Faustman, demonstrated that multiple injections of the vaccine given to patients with long-standing type I diabetes – an autoimmune disease – produce major changes in the immune system, restoring some back to normal, though a full cure and restoration of normal blood sugars has not yet been reported (click here). Italian researchers, using the same multiple BCG vaccination approach and the same potent strain of BCG, have demonstrated that patients given the vaccine after their first MS attack are up to 50% less likely to develop full-blown multiple sclerosis than similar patients not given BCG (click here), and that those who are eventually diagnosed with multiple sclerosis experience a more benign disease course. Click on the graphic to the left for a visual representation of BCG's effects on MS. Further studies are expected to explore whether aggressive treatment with BCG may temper or stop already established MS.

In addition, early studies indicate the vaccine can protect against allergic asthma (click here).  Retrospective studies have demonstrated that BCG may protect against a range of childhood cancers (click here). Other studies have shown that children infected with human tuberculosis bacteria before the age of seven have an extremely low incidence of developing multiple sclerosis (click here), hinting that the TB bug changes the immune system profoundly, and may impact a range of diseases.

The above benefits, as significant as they are, may only scratch the surface of BCG’s potential. The vaccine appears to work by altering the workings of the immune system at the genetic level (click here). Because it works on the genes themselves, the effects of the vaccine are long-lasting, and the vaccine's effectiveness appears to increase with time. Thus, a set of two or three vaccinations with BCG may offer robust defense against a wide variety of the autoimmune diseases that are now becoming epidemic in developed nations.

Evidence of Hygiene Hypothesis
(click to enlarge)
Tuberculosis is caused by a type of germ called mycobacteria (click here). The human immune system evolved in the presence of mycobacteria, which have been found in the bones of 70,000-year-old cave dwellers (click here). Over the last 40 or 50 years, though, as the developed world has become increasingly focused on hygiene and cleanliness, mycobacteria have been largely eliminated from the populations of First World nations. At the same time, autoimmune diseases and allergies have become epidemic in the same regions (see graphic to the right). The “old friends” or hygiene hypothesis (click here) suggests that the absence of the bugs that were our evolutionary companions has led our immune systems to go haywire.

Think of it like this: one spouse in a long married couple that first met in grade school suddenly exits the relationship. The remaining spouse is confused, disoriented, and likely to behave in unpredictable and perhaps self-destructive ways. According to the old friends hypothesis, this sort of disorientation in the immune system is driving a startling rise in diseases such as MS, lupus, diabetes, and fibromyalgia, all of which were much rarer even just 50 or 60 years ago when mycobacteria infections in humans were still common worldwide. Since BCG reintroduces mycobacteria into the body, it may help restore balance to immune systems that evolved with constant exposure to such bacteria.

Unfortunately, a variety of factors are hampering research into the benefits of BCG. Modern studies exploring the use of the vaccine to combat autoimmune and other diseases are still in their early stages, and many questions remain. The vaccine is manufactured using live but inactive bacteria, meaning its potency varies depending on the manufacturing facility. In her type I diabetes studies, Dr. Faustman uses a very potent version of the vaccine manufactured in Japan which is not available in North America. In fact, BCG isn’t available anywhere in North America, as the last BCG factory in the region stopped production in 2016, due to manufacturing issues and the low profit potential of the drug (click here). Additionally, queries regarding the number of vaccinations needed for full potency as well as the most optimal methods of safely introducing BCG into the human body are still to be answered.

The most significant impediment to the development of BCG as a therapy for autoimmune and other diseases, though, is a severe lack of funding. Since the drug is nearly a century old and quite cheap (single doses cost pennies in Third World nations) there is very little to incentivize the for-profit medical establishment to get behind the research. The reasons for this are myriad, but boil down to the obscene fact that all too often profits take precedence over patients in our current twisted model of medical research, which is more often propelled by the drive for ever-increasing revenues than by scientific imperative. Many potentially paradigm-shifting therapies like BCG have been left to die on the vine simply because they lack blockbuster profit potential. MS and diabetes have become mega industries generating yearly revenues of $25 billion each, creating a status quo that discourages disruptive innovation. We can’t kill the geese that lay the golden eggs, now, can we?

Research into the BCG vaccine holds tremendous possibilities for fundamentally changing the treatment landscape for a wide variety of terrible diseases that are being seen with dramatically increasing frequency, including multiple sclerosis. In a perfect world, or even a less imperfect one, massive resources would be devoted to investigating BCG and other treatments that hold great promise but little profit potential. Instead, innovative researchers like Dr. Faustman and her colleagues are left to work in the shadows while a seemingly never-ending stream of “me too” drugs are brought to market, fueling massive industries devoted to treating diseases, not curing them.

If only a fraction of the monies spent developing blockbuster drugs that keep patients perpetually dependent upon them were dedicated instead to seeking cures or researching innovative therapies like the BCG vaccine, modern medicine and the patients who find themselves stuck in the belly of the beast would be much better served. As they say in the X-Files, the truth IS out there. And it may just be hiding in plain sight.

Here’s a terrifically informative video of Dr. Faustman giving a presentation on her work. Definitely required viewing:

On a completely different note, I was recently interviewed for an article that appeared in The Accelerated Cure Project's latest newsletter (click here). For those who might be curious about what I actually sound like, the piece includes a link to the audio of our original interview. God, I hate the sound of my own voice, and I think it may just be impossible to say “um” and “you know” more than I do during the interview…

Monday, January 15, 2018

Some Wheelchair Kamikaze Film and TV Recommendations

Dealing with multiple sclerosis, especially as it advances, can be an all-encompassing, overwhelming pain in the buttocks. We all need our diversions and these can be increasingly hard to find as the disease diminishes access to the outside world, especially during the winter months when wonky limbs and overwhelming fatigue can make it almost impossible to get outside without assistance. Thankfully, in this age of streaming media on electronic gizmos of all shapes and sizes, there’s a seemingly infinite universe of high-quality films and TV shows available for the watching, so watch I do. Nothing like losing yourself in a great flick or binge-watching an engrossing TV series to temporarily keep thoughts of the MS beast at bay.

Last year I posted a list of some of my favorite, somewhat obscure films (click here). I figured it’s about time to put together another such inventory – especially since I’m not in the mood to write yet another essay excoriating the MS status quo or plumbing the depths of my own experience with the disease. Time enough for that later, but for now here’s a list of some of the movies and TV shows I’ve been keeping myself occupied with of late.

There are a few oldies but goodies sprinkled in here, as well as some foreign fare. For those who are put off by the prospect of subtitles, I’d urge you to give at least one or two of these suggestions a try, as I’ve found that watching foreign flicks is like virtual tourism. I love soaking in the little details and differences of life in foreign lands, from local social customs and dress to such esoterica as the differences in light switches and bathroom fixtures, even if it's only by way of TV screen. Nothing like taking a short trip to Paris or Belgium while sitting in your wheelchair, stuck in your living room wearing nothing but your skivvies. And I promise, if what you're watching is good enough, before you know it you won't even realize that you're reading subtitles.

Please feel free to comment on any of my selections or to supply a few of your own in the comments section of this post. Enjoy…


The Grand Hotel Budapest – This quirky gem by director Wes Anderson is a sheer delight. A visitor to a long in the tooth but once grand hotel is told an enchanting tale of the venue’s glory days by a stranger he meets in the lobby. The film swoops and swerves as it follows the adventures of the hotel’s once legendary concierge and his sidekick lobby boy as they traverse a fictionalized and fantasized Europe in the time between the two world wars, getting mixed up in all sorts of absurdist escapades along the way. This is kookiness and eccentricity at its best, filled with heart, sentiment, tremendous humor, and a sense of pure revelry. Available to rent from Amazon video.

Boy – from the same director as Hunt for the Wildepeople (Taiki Waititi) – which I recommended in my last list – this charmer from New Zealand is the coming-of-age story of an 11-year-old Michael Jackson obsessed Maori boy as he gets to know his miscreant father, who is just back from a stint in jail. Set in 1984, the film is original and whimsical, heartfelt and idiosyncratic, as we follow the father’s comically obsessive search for ill-gotten money he buried in a field years before, employing the help of his inept outlaw gang and his son’s friends and acquaintances. Included are priceless reenactments of some of Michael Jackson’s most famous videos, including this Maori version of “Thriller.” Available for streaming on Amazon Prime…

The Swimmer – This all but forgotten 1968 Film is perhaps more pertinent today than when it was made 50 years ago. Starring the great Burt Lancaster as what initially seems to be a gregarious and successful ad man, The Swimmer follows this character as he makes his way across a wealthy Connecticut suburb one beautiful summer day, on a quixotic quest to swim home by stopping in his neighbors’ backyards and doing one lap in each of their pools. At each stop, the reality of the character is slowly revealed, his initial polished veneer stripped away bit by bit. The film explores the shallowness of a consumerist society that defines the value of a human being by the material goods they possess and shines a light on the lies we tell to others as well as the ones we tell ourselves. Based on a John Cheever short story, some of the cinematic techniques used seem a bit dated now, a half century after the film’s production, but the themes it explores and Lancaster’s stellar performance transcend any such quibbles. Available for rent on Amazon video.

Let The Right One In – this Swedish film focuses on a bullied 13-year-old boy who is befriended by his new neighbor, a mysterious 12-year-old girl who he only sees at night, and who sometimes smells a little funny. Okay, I’ll let the cat out of the bag – she’s a vampire, but I would hardly label this a vampire film. Let The Right One In tells a story of affection, devotion, alienation, and manipulation in a stark and intimate way. Although there is some blood spilled along the way, the story is more existentialist than horrific. Beautifully shot and directed, the film is set in a desolate and icy town outside of Stockholm. This is a cerebral film that leaves plenty of room for interpretation and is one of those movies that sticks with you for quite a while after viewing. Let The Right One In was remade in an English version as Let Me In, which is also quite good but a bit more straightforward in the telling than the original. I personally prefer the Swedish version, but the two films are good enough to warrant watching both. Start with the original Swedish version, though, unless you just can’t stand the thought of subtitles. Both films are available for rent on Amazon video.

TV shows:

Broadchurch – this magnificent British crime drama features a big-city police detective with skeletons in his closet who finds himself reassigned to a small coastal town in northern England. The show is three seasons long, with eight episodes per season. Seasons one and two deal with the murder of a young boy and its aftermath, which threatens to tear all involved and the town itself apart at the seams. Season three focuses on the investigation of a sexual assault, while the principles still contend with the emotional fallout of the crime investigated in the first two seasons. This show is about as good as it gets, with acting, tone, and content all achieving perfect pitch. The characters are intricate, the writing spot on, and the scenery itself breathtaking. I can’t recommend Broadchurch highly enough. Available for streaming on Netflix.

Hotel Beau Sejour – I absolutely loved this Belgian show. Kato, an appealing young woman, wakes up to find her own murdered body in the bathtub of an old hotel undergoing renovation. Confused and disoriented, she makes her way back to town and slowly realizes that she is indeed dead, but that five of her friends and family can still see her. Determined to unravel the mystery of her murder (she can’t remember anything from the night of her death), she sets about trying to assist in the solving of the crime as best a ghost can. As Kato struggles to uncover the truth, she discovers the secrets and deceptions of nearly all involved, secrets that even those who hold them are loathe to confront. I found this 10 episode series to be addictive, so much so that binge-watching seemed to be the only option. An added bonus, for me at least, is that the characters speak Flemish, a language I’d never before heard spoken and which seems to be a mix of Dutch, German, French, and English. Again, I’d urge not to let the prospect of subtitles deter you. Though there are some lapses in logic – why does a ghost need to wear a helmet when riding a motorbike? – this is a terrific show. Available for streaming on Netflix.

The Returned – this French series is spooky and disconcerting in the best possible way. Set in a remote French town that has suffered through a series of past tragedies, the community is once again rocked when some of its dead start returning in seeming perfect health and at the same age they were when they died. They have no sense of their own deaths and have no idea how or why they were resurrected. Shot in muted colors that perfectly match the mood of the series, The Returned explores the wounds of what might have been, and whether or not that those who were once given up for lost can ever truly be fully recovered. Throw in the resumption of a series of killings that had stopped years before, and you have the makings of an engrossingly moody Gallic meditation on the circle of life and the nature of good and evil. The show is two seasons long, eight episodes per season, and is available for streaming on Netflix. (Please note, this series spawned several remakes, including an absolutely horrendous American TV network version and a word for word English translation of season one that aired on the A&E network. I haven’t seen the latter, but only one season was produced, so the A&E version does not come to any resolution. This version is also available on Netflix, though, so please make sure to pick the original French version, which was titled Les Revenants).

Glitch – this is an Australian take on The Returned. It’s a markedly different show than The Returned, absent the moodiness and mystery of the original, but is excellent in its own way. Glitch doesn’t spend much time contemplating the metaphysical ramifications of resurrection, instead placing its focus on the personal histories of seven folks who have clawed their way out of the cemetery of a small western Australian town – most are from different historical periods – and on the science that brought them back. There are some shady characters about, most connected to a suspicious pharmaceutical company located in the vicinity. Each of the resurrected has a fascinating backstory, which they only start remembering in pieces. Much of the show is driven by each character attempting to put together their own personal history and the circumstances of their death. As the show progresses, it becomes more bittersweet than spooky and evolves into more of a thriller than a study in horror or philosophy. Despite its differences from The Returned, both shows had my wife and I hooked early on. Glitch is available for streaming on Netflix, but be forewarned that to date only two seasons have been produced, with the third seemingly still up in the air. The show doesn’t come to any hard resolution, but I found it so enjoyable that it warranted a mention regardless.

Hope you enjoy some or all of these picks. As mentioned earlier, please feel free to use the comments section to voice your own opinions or offer some viewing suggestions for fellow WK readers.

WHEELCHAIR KAMIKAZE SNEAK PREVIEW: I recently conducted a 90 minute interview with a naturopathic doctor who specializes in treating MS patients. The interview is jampacked with lots of important information and actionable ideas. I should be posting the first part sometime in the next several weeks – I have a lot of transcribing in front of me – and I think this interview will be of great value to WK readers.

Sunday, December 31, 2017

New Year’s Eve Through MS Eyes

(This essay was first posted two years ago. Guess this makes it a golden not so oldie, but it's timely and the sentiments expressed will hold true as long as MS remains my unwanted life partner…)

Back in in the days before I got jumped by MS I always loved New Year’s Eve. While many of my fellow habitual night crawlers derided the night’s festivities as “amateur’s hour”, a time when those less accustomed to nocturnal hijinks were apt to get sloppy and make fools of themselves, I embraced the ringing in of the new year con mucho gusto. Never content with just one party for the duration of the night, my friends and I would go on a kind of New Year’s Eve tour, hitting four or five shindigs and nightclubs before heading home well after dawn on January 1. The sentimentality of the holiday, with its tacit promises of sins forgiven and futures bright with hope held me in its thrall.  Though I seemed to live in a state of perpetual neurotic dissatisfaction, I also brimmed with expectations that bigger and brighter days were waiting just over the horizon. New Year’s Eve was the one night a year that this heady brew of emotions and expectations were codified into celebration, to be shared with friends and strangers alike.

For sure, my fondness for the holiday has its roots in my early childhood. My mom and dad divorced when I was three, and for several years after the split my mom and I lived with my grandmother and my unmarried aunt. On New Year’s Eve my young, single mom – who herself loved the nightlife – would head out with her friends into the NYC of the swinging 60s, and my grandmother, aunt, and I would watch Guy Lombardo and his Royal Canadians playing old timey big band hits for the well-heeled crowd at the Waldorf Astoria Hotel, broadcast live to our ragged black and white console TV. We didn’t have much money and lived in a building in the Bronx that was closer to a tenement than a high-rise, but our lack of means did nothing to diminish the excitement and expectations of the evening.

Though I was only four or five years old, on New Year’s Eve I was allowed to stay up till midnight to take part in a family tradition that stretched back decades. We didn’t have any fancy noisemakers or horns, but at the stroke of midnight, as confetti and balloons floated down on the well to do at the Waldorf and Guy Lombardo’s boys played “Auld Lang Syne”, my grandmother, aunt, and I grabbed sturdy but well-worn metal pots and pans. Then, using big spoons as drumsticks, we burst into the hallway of our apartment building, banging with joyous intensity on those old, scarred cooking implements, creating a raucous racket and shouting at the top of our lungs “Happy New Year’s!” Most of the other residents of the building joined us in creating a jubilant and low rent but somehow defiant cacophony, delirious and intoxicating stuff for the very young me. I daresay that for those few moments we had a lot more fun than the swells at the Waldorf.

When I grew older, as a young adult I fully embraced the revelry of the holiday. I had quite a few memorable New Year’s Eves in my late teens through my mid 20s, from seeing the new wave band The Waitresses playing a show at 5 AM at the famous Peppermint Lounge to bumming cigarettes from a then barely known Howie Mandel at an MTV “after party” that rollicked on and on as if it might never end. I recall with great fondness stumbling out of a nightclub with a group of deliriously intoxicated friends and madly howling at the moon as the last seconds ticked away on one long ago year. As I transitioned into full adulthood, mixed in with raucous annual celebrations were the occasional intimate, more romantic New Year’s get-togethers with lovers and close friends. No matter the circumstances, though, the night never passed without champagne and good cheer, and always kindled within me expectations of bigger and better things to come.

Now, nearly 13 years since I was diagnosed with Primary Progressive MS, the night carries with it a much more complex and troublesome mix of emotions. For the first several years after my creeping paralysis struck, while I was still relatively able bodied, my wife and I would host New Year’s Eve parties, more sedate than my revelries of the past but good times nonetheless. Now, with my body increasingly compromised and my stamina waning, even a small gathering of friends can prove taxing. This New Year’s it was just my wife and me watching celebrations from around the world beamed into our living room in high definition on our big-screen TV, images so crisp and detailed it seemed as though I could step right into them. That is, if I could step.

Despite my best efforts to stay fixed in the moment, I soon found it impossible to watch millions of people celebrating without enviously contrasting their situation with my own. With nary a thought given to their tremendous good fortune at simply having limbs and senses intact, the televised multitudes danced and sang, drank and strutted, laughed and hugged and mingled and voiced exuberant expectations about a future brimming with possibilities. Lubricated by flowing booze and the magic of the night, all could convince themselves that the coming days held better fortunes then those which now belonged to history.

For the healthy masses, New Year’s Eve crystallizes the reality that the future is but a blank canvas, the images to be painted on it not predetermined but subject to the will of each individual. All but the most intransigent of difficulties will give way to effort, ingenuity, and discipline. Reality is but a construct of the human mind and the emotions it creates, and as such can be born anew once the self-defeating habits of the past are no longer allowed to dictate actions in the present. Not that these kinds of changes are easy, but with sound body and mind anything – anything – is possible. Sadly, it took my getting sick for me to fully understand this, but there is no greater truth.

And here I sat in a wheelchair – a wheelchair, goddamnit – trying my best to not begrudge the healthy, to vicariously share in at least some of the delirium, to laugh along with them and not let the sneaky tears that kept making their way to the corners of my eyes expose the turmoil that roiled within. There is indeed a reason they call progressive disease progressive. Physically, this last year has been a rough one, with old symptoms getting noticeably worse and new ones breaking the surface. Activities that could be accomplished with relative ease just a year ago are now at times tortuously difficult, and some of those that had been difficult have become damn near impossible. And by activities I don’t mean anything as devilishly complicated as walking or tying a shoe, but rather firmly gripping a fork, or struggling into a sweater, or on bad days, even just staying out of bed for more than four or five hours at a time. 

Unlike those healthy New Year’s Eve revelers on TV, no amount of willpower or change of habits will arrest this bitter physical decline. Though for the most part my spirit stays strong, in the face of this insidious physical onslaught and its accompanying indignities I find it impossible to not at times give way to the weight of it all, having my breath taken away daily by the shocking realization that this is no dream that I can wake from, but instead a concrete reality in which I am being forced to watch myself slowly wither away. The mantra of “staying in the moment” does help to keep me grounded, but there are also times when the moment just sucks. Though I can and do fantasize about a future free from illness, my utter conviction to stare this bastard straight in the eyes lands such fantasies well into the realm of the far-fetched, right there alongside my old dreams of becoming the next Mick Jagger or Philip Roth.

New Year’s Eve is a time to look back and project forward, and for the healthy this shedding of the old and embracing of the new can be cathartic, if even just for a few hours. This New Year’s brought me no such respite, though, as a look back illuminated the losses suffered these past 12 months, and peering too deep into the future can be perilous, a glimpse at the dark at the end of the tunnel, a glance at an unthinkable void. 

Yet I am not without hope. I keep myself immersed in the latest research and MS news, and though much of it is, quite frankly, garbage, there are approaches that do show promise. Perhaps I am delusional, but even through this morass of illness and increasing disability my resolve to not back down sometimes bends but doesn’t break, even as I acknowledge that merely stabilizing my disease state is at this point quite a longshot. But I know for a fact that sometimes longshots do come in. After all, I’m a guy who once won $15,000 in the Florida lottery, so I’m proof positive that you’ve got to be in it to win it.

So, as I sat there watching the partiers on TV, wrestling with my complicated and disconcerting mass of emotions, when the clock struck midnight I chugged some champagne and kissed my wife, while my inner five-year-old banged on pots and pans and screamed at the top of his lungs, “Happy New Year’s!”…