Tuesday, January 17, 2017

Ocrelizumab 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 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.

Ocrelizumab, 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, 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. Ocrelizumab 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 ocrelizumab 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 ocrelizumab 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 ocrelizumab 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…

.

Thursday, January 5, 2017

New Year's Eve Through MS Eyes (repost)

(This essay was first posted about one year 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, for 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.

I suppose 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 maybe 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, and, using big spoons as drumsticks, 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 good fortune that would far eclipse those which now belonged to history.

For the healthy masses, New Year’s Eve encapsulates 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 there 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. My strange and thus far indecipherable mix of endocrine dysfunctions, creeping paralysis, and hideously painful deteriorating joints (courtesy avascular necrosis, a very rare side effect of the intravenous steroids once used to try to beat back the creeping paralysis) has become more intractable than ever, defying all efforts, mainstream and alternative alike, to slow things down.

Unlike those healthy New Year’s Eve revelers on TV, no amount of willpower or change of habits will arrest this bitter physical decline. I continue to fight my disease on all fronts, employing a dizzying array of supplements and medicines to lessen the impact of some symptoms, and undergoing treatments both holistic and traditional at which my condition seems simply to sneer. 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. My mantra of “staying in the moment” does still help to keep me grounded, but there are also times when the moment just sucks, no two ways about it. 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.

And even 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!”…



Wednesday, December 28, 2016

So Long, 2016…

(For those who receive this via email, this post contains a video, which can be viewed on the Wheelchair Kamikaze website – click here)

Just a few things to wrap up it up as we bid adieu to 2016, a year that has seen much tumult and turmoil for so many. My Spidey senses are telling me that 2017 may make 2016 look like a powder puff, but then again, three decades ago my Spidey senses told me that I would be the next Mick Jagger, so what the hell do they know? Stupid Spidey senses.

On a much more upbeat note, on Tuesday, December 27, 2016, Wheelchair Kamikaze received its 2.5 millionth page view, according to statistics provided by Google. All I can say to that little factoid is – mind blown. When I first started the blog I never expected more than a couple of dozen people to look at the thing, and even though I strongly suspect that at least 2.45 million of those page views are directly attributable to my mother, I’m still gobsmacked.

Wheelchair Kamikaze hit 1 million page views back in January 2014, about 5 years after I started the blog. Now, we’ve added another 1.5 million page views in only 3 years. Again – mind blown. All I can say is thank you thank you thank you thank you thank you thank you thank you thank you thank you thank you 2.5 million times to everybody who has ever laid eyes on these pages. Though my stupid Spidey senses never saw the unfortunate circumstances that led to Wheelchair Kamikaze coming down the pike, I am eternally grateful to everyone who has animated these pages with their comments, input, and presence. 

We are all in this together, folks, and the only way out is through. You’ve all helped me stumble my way through the body and mind twisting experience of multiple sclerosis, and if I’ve been able to help some of you shoulder the burden even just a little bit then at least there has been some method to the madness. Okay, all together now – MS SUCKS!

For those who might want to read a bit more about yours truly and the back story of the blog, Healthline.com has published a very nice article about WK in conjunction with the blog taking 2nd place in the website’s Best Health Blog contest (click here). I’d like to profusely thank the writer who penned the article, Elea Carey. She somehow managed to wrangle the veritable deluge of self-indulgent verbosity I sent her way in response to some simple interview questions into a succinct and elegant piece of writing. Maybe I should hire her as the full-time editor of this blog. Lord knows I need one. Stop me before I compound sentence again.

Okay, enough about me, I’ll end this last blog post of the year with an actual MS related item. The much anticipated FDA review of Ocrelizumab, the first drug that has a chance to be approved for the treatment of PPMS (along with an almost guaranteed approval for RRMS), has been delayed. Although the drug was initially slated for FDA review on December 28, that date has now been pushed back to March 28, 2017, due to “manufacturing issues” (click here). I’ve previously written fairly extensively on Ocrelizumab and its late stage trials (click here), and I’ll certainly have more to contribute in the coming weeks. 

Although the medical press is practically hyperventilating about the first drug that stands a very good chance at being approved for use in people with PPMS, there are some valid reasons for concern regarding this product. I’m hoping to interview a representative from Genentech, the manufacturer of Ocrelizumab, which, if it happens, should be pretty interesting. I’m also working on getting some interviews with other prominent figures in the MS world, so stay tuned…

All righty then, here’s to a happy new year to all, and may 2017 bring each of us much more good than bad. I’ll leave you with the following tune from a band I’ve loved ever since I first saw them as a high school sophomore in the late 1970s. To hell with my tingling Spidey senses, how about some unabashed optimism to ring in a brand-new year…

Thursday, December 22, 2016

Happy Holidays, and Results from Our Donation Poll

 

Ho ho ho, Merry Christmas, Happy Hanukkah, Good Festivus, and Happy Kwanzaa. And for anybody not covered by the previous salutations, I wish you a joyous winter solstice.


Okay, folks, the votes are in for our holiday donation contest, and it looks like the Tisch MS Research Center of New York has won in a landslide victory. The Tisch Center garnered 63% of the votes in our poll to determine which MS nonprofit should get the $500 donation derived from the prize money Wheelchair Kamikaze won in Healthline.com's "Best Health Blogs" contest.


Ultimately, over 210 people voted in our contest, with about 130 of them voting for the Tisch Center, so a resounding victory all around. This takes nothing away from the other nonprofits I offered up for votes: The Accelerated Cure Project, The Buffalo Neuroimaging Analysis Center, and The Multiple Sclerosis Association of America. All of these organizations are doing great things for the MS community and are certainly deserving of your own holiday gifts if you are so inclined. You can read more about all of them by (clicking here).


Oddly, the blog post soliciting votes for these groups was viewed almost 1200 times in the past week but only slightly more than 200 people voted in the poll. Not sure why somebody would read the post and not vote, but c'est la vie. Maybe it had something to do with Russian hacking or some other nefarious goings-on. Sad.


I will be making the donation to the to the Tisch Center as soon as I receive payment from Healthline.com, which is on its way. This past week I visited with Dr. Sadiq, the lead researcher of the Tisch MS Research Center, and he was extremely excited about the prospects for The Center's upcoming Phase 2 regenerative stem cell trial for MS patients, the first such trial to receive FDA approval. In preparation for the upcoming trial, The Center is about to start construction of the world's largest MS stem cell laboratory in the world, and is also about to publish the results of the first phase of the trial. The Phase 2 trial is currently scheduled to start in June, 2017. In addition to stem cell research, The Tisch Center is also delving into many other aspects of the MS mystery, and Dr. Sadiq had some very encouraging things to say about the whole of the Tisch Center's research efforts. He feels that his researchers are closer than ever before to unraveling some of the core mysteries of Multiple Sclerosis.


Not sure if I'll get a chance to put a post up next week, so let me take this opportunity to wish everybody a happy and healthy 2017. Here's hoping that the new year brings only good things to each and every one of us!


Thanks for reading Wheelchair Kamikaze, and for breathing life into this blog. My appreciation for all who visit these pages is beyond words…


Here's some Christmas cheer from The Godfather of Soul…





Friday, December 16, 2016

WK Takes 2nd Place in "Best Health Blogs" Contest!


Hey folks, thanks to your votes Wheelchair Kamikaze took 2nd place in Healthline.com’s “Best Health Blogs” contest! This is really a terrific honor, particularly because of the fierce competition – 382 other blogs were nominated to participate in the contest. Big congratulations to the two 1st place winners who apparently tied in the voting, “Lizzie’s Lungs” (click here) and “ALS and Wellness” (click here), as well as 3rd place winner “Early Onset Alzheimer’s” (click here). And of course, a huge thank you to Healthline.com (click here) for running the contest. Although Wheelchair Kamikaze has been honored as among the top MS blogs in the past, I believe this is the first time it’s been recognized as one of the best health blogs in general. BTW, Healthline's graphic department came up with the above image. I'm not THAT much of an egomaniac…

Healthline has generously awarded Wheelchair Kamikaze $500 for its second-place finish. I’d like to donate this prize money to a worthy MS nonprofit, and I’d like Wheelchair Kamikaze readers to pick which organization should get the big bucks. We’ll do this via an online vote, much the way Healthline’s contest winners were chosen. I’ve taken the liberty to nominate four worthy organizations from which to choose. Here’s some brief background on the chosen organizations to help inform your vote. I’ve arranged the candidates in alphabetical order.

  • The Accelerated Cure Project (click here) – The ACP is the organization administering the iConquerMS project (click here), a patient-centric research project in which MS patients can take a personal stake in advancing the cause of MS research by completing a series of online questionnaires, suggesting research topics of importance to them, and providing their feedback on research studies. By “crowdsourcing” a massive amount of data supplied by MS patients themselves, iConquerMS is compiling an unprecedented database on all aspects of MS that is open to researchers worldwide. This huge pool of information should reveal trends and insights into and about the disease that otherwise would have been missed by looking at smaller pools of data. I strongly encourage all readers to visit the iConquerMS website to sign up and begin participating in this tremendously important project. Your information has power, and together we can conquer MS. (Full disclosure: I am a member of the iConquerMS engagement committee).
  • The Buffalo Neuroimaging Analysis Center (click here) – BNAC is a research organization devoted to shedding light on the mysteries of multiple sclerosis and other neurologic diseases through the use of innovative imaging techniques and advanced analytic tools. The group did some of the first rigorous scientific research on CCSVI when Dr. Zamboni’s vascular theory of MS first made headlines, producing findings that cast some doubt on the causative role of venous abnormalities in MS. Their research has expanded to include the role that vascular abnormalities might play in exacerbating a wide range of neurological disorders. Lead researcher Dr. Robert Zavidanov directs a team of medical researchers and scientists of a variety of disciplines, who, among many other projects, have probed the role that gray matter lesions and inflammation of the tissues that surround the central nervous system play in the MS disease process. BNAC has pioneered many revolutionary imaging techniques. Their work promises to change in a fundamental way our understanding of Multiple Sclerosis. (Full disclosure: I’m on the patient advisory board of BNAC).
  • The Multiple Sclerosis Association of America (click here) – The MSAA provides vital services and support to MS patients throughout the United States. Programs include a Helpline with trained specialists; award-winning educational videos and publications, including MSAA’s magazine, The Motivator; safety and mobility equipment distribution; cooling accessories for heat-sensitive individuals; educational programs held across the country; and Lending Library among other services. For MS patients in financial need, the Association provides assistive equipment and cooling garments free of charge, as well as financial assistance for those who cannot afford to get MRIs. The scope of services and information provided by the Multiple Sclerosis Association of America is truly astounding, and even includes a smart phone app that helps patients manage their MS. Their website is a terrific resource for information on all things MS. I encourage all Wheelchair Kamikaze readers to visit the MSAA website and poke around, it’s a veritable treasure trove of information and vital services.
  • The Tisch MS Research Center of New York (click here) – The Tisch Center is a worldwide leader in cutting-edge multiple sclerosis research, and is currently in preparations to begin the first FDA approved Phase 2 regenerative stem cell trial in MS patients ever conducted, expected to get started this June. The Center is building the largest stem cell research laboratory in the world, and its staff of world-class researchers has developed proprietary methodologies that transform raw mesenchymal stem cells into cells specific to the central nervous system, which should prove to be much more capable of repairing the damage done by MS than the raw cells themselves. Under the guidance of Dr. Saud Sadiq, the Tisch center is involved in a wide variety of transformative MS research projects, from identifying new disease biomarkers to understanding the mechanisms behind disease progression. The Tisch MS Research Center is totally devoted to finding the cure for Multiple Sclerosis, which is of course the ultimate desire of every MS patient and all those who love them. (Full disclosure: Dr. Sadiq is my personal neurologist).

Please take a thorough look at all of the above candidates, and vote for whichever organization you would like to see receive the $500 awarded to Wheelchair Kamikaze by Healthline.com. The poll is located at the top of the left-hand column of this page. I’ll leave the poll open for 7 days, so the results can be determined just before Christmas. Of course, all of these organizations are great candidates for your own charitable giving, should you be so inclined. Ho Ho Ho…

Once again, thanks so much to everyone who voted for Wheelchair Kamikaze in the best health blog contest…

Friday, December 9, 2016

Shingled Out – Updated

(A quick thank you to all who have voted for Wheelchair Kamikaze in Healthline.com's "Best Healthcare Blog" contest. Voting continues until December 12, (click here) to cast your vote…)


Note – this is an updated version of this post, which was originally published earlier today. This update includes further information on the shingles vaccine, added at the end of the essay, due to some concerns raised by readers over the safety of the vaccine when used in MS patients. Just wanted to ensure that these issues were addressed. 

Well, it looks like the holidays have come early to my house, and rather than Santa bringing me that 1956 Porsche I've always wanted, I instead got the shingles. Yay. Guess I was on St. Nick's "naughty" list…


About two weeks ago I started feeling vaguely unwell, suffering from the kind of symptoms one typically gets before the onset of the flu. Just generally achy, no appetite, and a tremendous amount of fatigue, even for an MS patient. A few days later I was assaulted by the worst headaches I've ever experienced, jolting bolts of excruciating pain that felt as if somebody was trying to impale my skull with a red-hot stiletto behind my right ear. The pain, which exploded from the bottom of my skull forward to the area above my right eyeball, came in waves about every minute or so, and was breathtakingly debilitating. I have a lot of experience with pain due to a degenerative bone condition called Avascular Necrosis, but the searing, twisted agony I was suddenly stricken with was beyond anything I'd ever felt or even imagined.


As I sat cradling my head in my hands, trying desperately to keep my skull from blowing apart, my wife quickly googled the symptoms I was experiencing. She came up with a condition called occipital neuralgia, which can develop in MS patients. The ailment involves inflammation or damage to one of the occipital nerves, which run from the base of the skull up through the scalp, and its symptoms seemed to precisely match what I was feeling. As this was all occurring on a Saturday night, there was little I could do but suffer through it. I was absolutely not going to go to a hospital emergency room, as I long ago resolved that before I would put myself through the existential, soul crushing misery of sitting in a New York City emergency room on a Saturday night I'd have to be suffering from something no less serious than a severed limb. Much better to lay moaning in bed waiting for my skull to combust.


The next morning I called my neurologist and told him what was going on, and he agreed that my symptoms sounded like occipital neuralgia. He phoned in a prescription for gabapentin, a drug also known as Neurontin, which is used treat nerve pain. The Neurontin did indeed reduce my pain level substantially, but also made me feel completely loopy and dumb as a box of nails. Still, not a bad trade-off, all things considered. Better stupid with a dull headache than smart with a skull trying to contain a thermonuclear blast.


Later that day I noticed a slight rash on my right forehead, an area in which I sometimes get a bit of psoriasis. For reasons that doctors really can't explain, many patients with nervous system diseases also get skin conditions like psoriasis or eczema. Ask a doctor about this strange correlation and they'll likely answer you with a string of polysyllabic mumbo-jumbo, because most physicians would sooner poke their own eyes out than utter the words "I don't know", but the truth is this connection has long been observed but is little understood. In any event, the skin on the right side of my forehead became more inflamed as the day went on, and started getting very tender as well. By that night I noticed little blisters appearing in the rash, and I started thinking "shingles".


The next day, Monday, I called my neuro's office and told them I suspected I had a case of shingles, and they told me to come right in. After a brief examination, the neurologist I saw confirmed that I probably had shingles, but advised me to see a dermatologist ASAP to nail down the diagnosis. I saw a dermatologist the following morning, and she concurred that I did indeed have shingles. I told her that I would rather have a spiral staircase, and she just stared at me blankly. I hate doctors with no sense of humor. She did say that the severe headaches I had experienced were typical for people developing shingles on their forehead and scalp, so that at least explained the pain I was feeling.


Shingles is a condition caused by the varicella zoster virus, also known as the herpes zoster virus. This is the virus that causes chickenpox, which was very common among children of my generation, back before most kids were given the chickenpox vaccine. I had chickenpox when I was six years old. The varicella zoster virus is a human herpes virus (click here), a family of viruses that also includes Epstein-Barr virus and the viruses that cause oral and genital herpes. In total, there are eight known human herpes viruses, which all share a common trait: once a person is infected with them, they are infected for life.


In the case of the varicella zoster virus, after causing chickenpox the virus goes into deep hibernation, taking refuge in the root cells of nerves. Later in life, usually when a person is older than 50, the virus can suddenly wake up and migrate down the path of the nerve to the skin, where it causes the painful rash that is the hallmark of shingles. There is now a shingles vaccine that can greatly decrease the chance of a person infected with herpes zoster to develop shingles, but I never asked for the shot. I'd seen countless commercials for the vaccine, and had thought to myself, "self, you should probably get that vaccine", but as I am generally nauseated by prescription drug advertising I refused to be swayed by the pharmaceutical companies' slick efforts to hawk their product. Stupid me.


While I did know that shingles involve a painful rash, I didn't know that the condition also commonly makes patients feel like absolute crap for weeks on end. Those initial flulike symptoms I was experiencing in the days before I developed the searing headaches and then the rash have blossomed into full-fledged misery, leaving me feeling like I just tried to kiss the "A" train between stops. I still have a dull headache, my muscles hurt, I feel feverish (even though I have no fever), and I'm so fatigued that I could easily sleep 20 hours a day. I'll be on antivirals for the next 30 days, which supposedly will shorten the duration of these symptoms. The blistering rash on my forehead is starting to crust over (yum), which is the first sign of healing. And, of course, as with any bug that strikes an MS patient, all of this has only made my neurologic symptoms much worse. My compromised extremities are less functional than ever, a frightening preview of what my continuing progression has in store.


I've been told to avoid contact with people until at least the end of this week, since there is a chance I could pass the virus on to folks who either never had chickenpox or were never vaccinated against them. The weird thing is that if I did pass the virus on to someone they would develop chickenpox, not shingles, since the first stage of varicella zoster infection is always chickenpox, no matter when you contract it. Avoiding people shouldn't be much for problem, as I can barely make it from my bedroom to the living room in my wheelchair. And who wants to see people anyway, when you've got a disgusting crusty rash on your forehead. Children would run screaming…


Please, take my advice – if you had chickenpox as a child, go get the shingles vaccine. I wouldn't wish what I'm currently going through on a dog. Actually, I wouldn't wish anything bad on a dog. I like dogs. Dogs are better people than most people.


Woof.


Addendum: numerous readers have sent notes advising me that because the shingles vaccine contains live virus they've been told it's a no-no for MS patients. Others, though, have reported getting the vaccine with no problems.


Here's more info on the shingles vaccine and MS, from the National Multiple Sclerosis Society Website:


"Zostavax is a live-virus vaccine to prevent shingles. MS neurologists do not recommend live-virus vaccines for people with MS because these vaccines can lead to an increase in disease activity. However, Zostavax is an exception because most people have had chicken pox earlier in their lives and therefore already have the virus in their bodies. Each person needs to discuss the potential benefits and risks of this vaccine with her or his healthcare provider."


For further info, a very comprehensive article about the shingles vaccine and its use in MS patients can be found at the Multiple Sclerosis Association of America's website (click here).


Bottom line, there seems to be some conflicting information out there regarding the safety of MS patients getting the shingles vaccine. This appears to be due to the complex nature of Multiple Sclerosis and the drugs used to treat it. Each patient is different, and no one-size-fits-all approach will cover all bases. Given my horrible experience with shingles, I'd say it's definitely worth a conversation with your neurologist to discuss whether or not you're a candidate for the shot.



(Warning, shameless self promotion ahead: Wheelchair Kamikaze has been nominated for Healthline.com's "Best Healthcare Blog" contest. If you feel WK deserves such an honor, please cast your vote on the contest webpage (click here). Just scroll down at the contest webpage until you see the blog name, Wheelchair Kamikaze is currently in fourth place).


Tuesday, November 29, 2016

Please Vote! – Wheelchair Kamikaze Nominated for Best Healthcare Blog Award

 
 

I'm proud to announce that Wheelchair Kamikaze has been nominated for "Best Healthcare Blog" in Healthline.com's annual best blog awards contest (click here). The winner of the contest will be decided by the votes of none other than the readers of the nominated blogs.


In fact, the nominations also came from blog readers, though I have no idea who nominated Wheelchair Kamikaze. I was completely unaware that the nomination process had begun, so I swear it wasn't me who proffered the nomination. But some very nice person or persons were kind enough to throw Wheelchair Kamikaze's name into the hat. Thanks, whoever you are. I had my suspicions as to who might have been the culprit, but my mom swears it wasn't her. Still, I have my doubts. When I was 26 years old she submitted a poem I had written in the third grade about how wonderful she was to the local Fort Lauderdale newspaper, which printed it – along with a hideous picture of me at eight years old, complete with coke bottle glasses and hair that looked like it was styled in a blender – on Mother's Day. This was just a few months after I had moved to the area and was just beginning to form a circle of friends. The day it was published was the day I learned how to spell "mortified".


Anyway, Healthline's Best Blog contest is decided by votes, so I'm asking all who appreciate these pages to cast a vote for Wheelchair Kamikaze (click here). As a matter of fact, you can cast more than one vote, since the rules allow for each person to vote daily. So, as they say in Chicago, vote early and vote often.


The voting actually started on November 21, so I'm a little late to the game because I've been engaged in hand-to-hand combat with some new and particularly unpleasant MS related crap. I'm like the butcher who backed into his meatgrinder and got a little behind in his work. Okay, just for dusting off that moldy oldie – which had them rolling in the aisles 60 years ago on the Borscht Belt (click here) – I think I deserve a vote or ten. And just my bringing up something as random and esoteric as the Borscht Belt should also be a vote-getter. Am I not just the most adorable thing… I'm not competitive or anything, but world domination has always been high on my bucket list. Today the blogosphere, tomorrow the world!


Healthline.com is offering a very generous $1000 prize to the winner of the contest. If I do win, half of the prize money will go to a worthy MS nonprofit, and it won't be the NMSS. Hey, here's an idea: I'll run a poll on the blog about which nonprofit should get the donation, on behalf of all of us. Won't that be fun? Voting ends on December 12, and, as I previously said, people can vote each and every day until the end of the voting period.


In all seriousness, writing Wheelchair Kamikaze has been one of the most rewarding experiences of my life. The fact that I've been able to help some of my fellow travelers on this rocky road that we've all been forced to follow leaves me humbled and grateful. The blog has allowed me to meet and interact with some of the bravest, most resilient, and remarkable people I've ever known, each fighting their own personal MS battle with immeasurable bravery and fortitude even in the face of the incomprehensible confusion and fear engendered by the disease. Wheelchair Kamikaze has given me a sense of purpose through my own struggle with the madness of Multiple Sclerosis, and I'm fairly certain I would not have made it this far without the support I have received from readers all over the world, many of whom have offered words of encouragement, kinship, and thanks that have more than once brought me to tears. I thank you all from the bottom of my heart.


If you care to cast a vote, please (click here). And once again, an immense thank you to each and every person who has helped make Wheelchair Kamikaze successful beyond my wildest dreams. I simply don't have the words to express the feelings I have for every patient, caregiver, and medical professional who has participated in WK these past seven and half years. What all of you have given me is simply priceless. And no contest win or lose will ever change that.


If you do vote, please use the search box on the contest page (click here) to find Wheelchair Kamikaze, as there are 383 blogs in the contest.


Thanks again for your support.




Addendum:  Thanks to everyone who has already voted. Don't forget, you can vote every day until December 12.


I understand there are several hoops you have to go through to vote. First, you need to find my blog among the list of 383 blogs that were nominated. The easiest way to do this is through the search box on the contest webpage, and just search for "wheelchair". This way you don't have to try to figure out how to spell Kamikaze, and the search engine will bring you right to my blog.


After you enter your email address and vote, you need to scroll up the page to find the little "capcha" box to prove you're not a robot. Then you will get a confirmation email on which you need to click a link to confirm your vote.


Geez, guess they must be super worried about voter fraud or something. It's easier to vote for president…




Friday, November 18, 2016

Why Must It Be So Damned Hard To Be Sick?

I’m fully aware that the concepts of “fair” and “unfair” are constructs of the human mind. Politely stated, stuff happens. We then process that stuff and sort it into any number of mental files, “fair” and “unfair” being but two of the many choices in the filing cabinets we all carry around in our heads. Yeah, it seems unfair that I got slammed with the MS stick, but so did 400,000 other people in the USA. It’s also unfair that I wasn’t born into British royalty, but, given my proclivity for drunken shenanigans, the royal family might think it unfair if I was. Then again, I’d probably fit right in…

That said, I do think it is unfair that people socked with chronic illness are forced to not only deal with the ramifications of their diagnosis but also with a medical infrastructure that often seems geared towards making being sick as difficult as possible. It’s as if having a terrible illness isn’t quite enough; most patients soon find that on top of their condition come layers of impediments that seem designed to make being infirm an exercise in frustration, aside and apart from the effects of the disease itself. Primary among the contributors to the difficulties encountered by the chronically ill are insurance companies, pharmaceutical companies, and the doctors who treat the illnesses themselves, an interlocking triumvirate that oftentimes seems intent on destroying the peace of mind of those unhappily forced into its grip. Let’s look at each of these elements individually, and explore the many fangs of this three-headed beast. 

First, we have the insurance companies, which are generally perceived as big, boring, faceless monoliths filled with human automatons making love to their spreadsheets and actuarial tables. The reality of the insurance industry is a bit different, though. Insurance companies are professional gamblers who look at the entire world as one big casino. By fastidiously crunching data accrued over centuries, insurance companies place bets tilted in their favor on almost every aspect of life, including life itself. 

In the case of the health insurers, the primary wager placed is that the money paid to them by the mostly healthy people they insure will far outweigh the money the company needs to pay out when the bet goes wrong and their customers get sick. Like any gambler, insurance companies hate to lose. When their wagers go south, they’ll shamelessly employ any number of unsavory tactics in an attempt to minimize their losses. For patients forced to deal with insurers who aren’t keen on making good their part of the wager, this means having to navigate intricate bureaucracies who play by rules largely of their own making, utilizing tactics designed to discourage and dismay those trying to get their fair due. 

Primary among these strategies is simply to delay making payments in the hopes that the patient will grow so incredibly frustrated they’ll eventually throw up their hands and give up. Insurers do this by putting as many obstacles in the way of the patient as possible, in the form of a labyrinthine paths to payment filled with large amounts of paperwork, endless requests for additional information, and a wall of bureaucracy meant to intimidate and appear impenetrable. Is there any less savory prospect than having to get on the phone with an insurance company representative to try to resolve a claim that the insurance company has arbitrarily denied? I’d rather try to brush my teeth with a flaming stick. 

In the nearly 15 years since my diagnosis, I’ve spent countless hours on the phone doing battle with insurance company demonoids intent on frustrating my every attempt at having them make good on their obligations. Requested paperwork, once delivered, is often mysteriously “lost in the system”, requiring it to be refiled all over again. Claims are passed from department to department in an apparently endless loop, with each department introducing a new set of rules and requirements. The phone reps themselves are not empowered enough to actually take any actions, meaning that most of what is said to them is simply wasted breath. Aargh! 

The key to getting eventual satisfaction (not to mention the money owed to you) is to never give up, even if it feels like your brain is about to blow through the top of your skull. In the words of Winston Churchill, "Never surrender!" If the phone rep is unable to give you a satisfactory answer, demand to speak to their supervisor. If that supervisor is uncooperative, demand to speak to their supervisor. Eventually, if it seems that you have run out of people to talk to, threaten the nuclear option: tell them you are going to get your state insurance regulators involved. This will usually lead to a miraculous resolution of your case. Unless of course you live in a state with lax insurance regulations, in which case you might try making hyena noises into the phone. 

Of course, one of the reasons the insurance companies are so loathe to make payments is the outrageous costs of medical procedures and pharmaceutical products. This brings us to the second member of our triumvirate of torture, the pharmaceutical companies. Contrary to popular belief, the pharmaceutical companies themselves are not inherently evil, they just smell that way. The first thing to keep in mind when thinking about the pharmaceutical industry is that pharmaceutical companies are not in business to produce cures. This may be difficult to grasp at first, but truer words were never spoken. Except maybe “never eat enchiladas after midnight”. The indigestion will kill you, and you've got enough problems. 

All of the major pharmaceutical companies are public companies, meaning that their stock is traded on the public stock exchanges. As officers in public companies, pharmaceutical executives are mandated by law to be beholden to their shareholders, not to the patients taking their drugs. The importance of this point cannot be overemphasized. Given this reality, a company making billions of dollars on a drug designed to treat a disease could potentially run afoul of their stockholders (and the law) if they came up with a drug that cured the goose that lays perpetual golden eggs. This is a classic conflict of interest. 

The tremendous profitability of "successful" pharmaceutical products has led Big Pharma to engage in many morally questionable activities. Believe it or not, more money is spent on marketing pharmaceuticals than is devoted towards the research and development of newer and presumably better drugs. Since the pharmaceutical companies themselves fund most late stage medical research – they are the only entities with enough money to do so – negative research results are often suppressed and never see the light of day. This means that the research our doctors rely on when making treatment decisions is inevitably skewed towards the positive. Supposedly independent research has often been found to have actually been written by ghostwriters in the employ of Big Pharma. The pharmaceutical lobby is one of the most powerful in Washington, practically ensuring that most of these ills never get properly addressed by our lawmakers. 

Having said all of that, the most insidious and pernicious way the drug companies impact patients themselves is their ongoing practice of bribing doctors to prescribe their drugs. Naturally, these bribes are dressed up in all manner of tuxedos and ball gowns, taking the form of “honoraria” or “consulting fees”. Doctors are paid copious sums to “educate” their fellow physicians, most often over expensive dinners at fine restaurants. Physicians are invited to “educational symposiums” which take place at luxurious resorts where most of the education seems to come in the form of 18 holes on a golf course. In one of their latest ploys, pharmaceutical companies ask doctors to fill out surveys which earn the physicians points that can be redeemed for all sorts of luxury goods (click here). 

How and why are these practices not illegal? Got me. Before MS forced me to retire, I worked in the music industry for one of the largest multinational entertainment companies in the world. If our company was caught paying radio stations to play the records we produced, people would go to jail. Now, what is more harmful to society, music companies paying off DJs, or drug companies paying off physicians? 

Thankfully, patients now have a resource by which they can find out just how much money their doctors are taking from pharmaceutical companies. The website “Dollars for Docs” makes it easy for patients to look up their doctors and find out exactly how much pharmaceutical company money their doctors pocketed from August 2013 to December 2014 (click here). I’m happy to say that my neurologist doesn’t even allow pharmaceutical company representatives into his clinic, and the fact that he doesn’t appear on the Dollars for Docs database confirms this. If your doctor does show up on the database and has pocketed tens of thousands of dollars of pharmaceutical company largess, it’s certainly within your rights to question them as to how these payments influence their treatment decisions.

Which leads us to the final element in our trilogy of torment, which, tragically, is often our physicians themselves. This is by far the most heartbreaking component of the obstacle path patients with chronic illness must navigate, as our doctors should be sources of comfort and care, not necessary evils. I consider myself extremely fortunate to have as my neurologist a man I not only respect but for whom I also have a very real affection. And I’ve every reason to think that the feelings are mutual. Sadly, in my contacts with literally hundreds of MS patients since I started this blog, I’ve found that the clear majority have a negative relationship with their neurologists, with feelings ranging from mild apprehension to utter disdain. 

As patients saddled with chronic illnesses, we are forced to enter long-term relationships with the doctors we choose to treat our conditions. As with any long-term relationship, it’s important to choose a partner who will be a positive in your life. And yes, I did say partner. The patient-doctor relationship should be a partnership, not a dictatorship. The patient should be respected and educated by their doctor, not talked down to or given orders without any explanation. 

Oversized egos seem to be abundant in those who don white coats and endeavor to be healers, and I suppose a certain amount of ego is only to be expected given the often daunting professional path taken by those who choose to treat intractable illnesses. But, contrary to what many of them seem to believe, doctors are not gods, and the fact is, just as in any profession, there are those who are great at their jobs and others, not so much. There’s an old joke that asks “What do you call someone who graduates from medical school with a C- average?”. The answer: “A doctor”. 

For patients with serious illnesses, it’s easy to feel at the mercy of the person we desperately hope will relieve the burden of our disease. Sadly, I’ve heard far too many stories of supposed MS experts giving patients horrible advice, putting them on treatments clearly wrong for that particular patient, or leaving the patient themselves to make serious treatment decisions while providing little or no pertinent information upon which to base those decisions. 

My first MS neurologist, the man who gave me my diagnosis, was I am sure a brilliant human being, highly respected in his field. Unfortunately, he had the bedside manner of The Great Wall of China, without the scenic views. I was shocked when at the end of our first appointment he handed me four videotapes – each promoting a different MS drug – and told me to go home, watch them, and come back with a decision as to which drug I wanted to try. I was so confused I could barely get a word out. At that point I had barely wrapped my mind around the fact I was seriously ill and knew absolutely zilch about Multiple Sclerosis. I was overwhelmed, frightened, and certainly in no position to pick a drug based on some slickly produced video presentations. Needless to say, this neurologist did not stay my neurologist for long. 

I do realize that in many parts of the country and the world MS specialists are hard to come by, so many patients have a limited choice of doctors. Even in these situations, though, it’s important to make sure that your questions get answered, that your fears and concerns are addressed, and that you are seen as a human being, not merely a body harboring a dread disease. Always remember this: your doctor works for you, not you for them. Just like anybody else you pay for service, your doctor is under your employ, not the other way around. As your doctor’s employer, you are free to fire them if you are not satisfied with the job they are doing. Now, that doesn’t give you the right to be disrespectful, impolite, or tyrannical, and even under the care of a top-notch physician dealing with MS can be a messy affair, both emotionally and physically. You owe it to yourself, though, to become an active participant in your treatment plan, and that means partnering with a doctor you can trust and respect, and whose motivations aren’t subject to suspicions of self-interest. If your current doctor fails to meet those criteria, I suggest you start looking for a new one. 

In short, being sick sucks. Not only do we have to deal with the ravages of disease itself, but also with all sorts of ancillary BS that makes life for those unfortunate enough to be stricken with chronic illness exponentially harder. Between the insurance companies, pharmaceutical companies, and some physicians, the impediments faced by those with serious illnesses can be almost impossible to confront. And yet confront them we do, with a quiet heroism that goes almost completely unacknowledged. 

The myriad obstacles thrown at people with serious illness are by and large beyond the comprehension of the healthy, as one cannot fully understand just how dysfunctional the modern medical establishment is until one is thrust into the belly of the beast.. We who are members of a club that none of us wanted to join share insights and experiences that are ours uniquely. As WC Fields famously said, all in all I’d rather be in Philadelphia…     



For those readers who might enjoy an MS essay of a more philosophical bent, my friend Mitch, who maintains the MS blog Enjoying The Ride, wrote a wonderful piece on acceptance in the face of ongoing disease progression (click here).     



RIP Leonard Cohen, who died last week at age 82. One of my favorite songwriters, I think he’s pretty much the man I always wanted to be. Though this isn't one of my most cherished of his compositions, this song is quite apropos for the times in which we now find ourselves…  

                   
                     

Thursday, September 22, 2016

How?

Given my tendencies towards intense introspection, I find it hard not to dwell on the “why’s” of my disease. Primary among these why’s is “why me?”, a question infused with self-pity that I know is best left unprovoked. I could quite easily drive myself half mad trying to figure all of the angles involved in this ultimately unanswerable query. If I’d made some different decisions in the past, might some alternate life path have avoided the Multiple Sclerosis landmine? Or would all roads eventually lead to Rome?

When I have allowed myself to stray down this tangled trail, a nasty battle always breaks out between my Buddhist and existential leanings, my inner Siddhartha calmly stating that there is no such thing as coincidence while my inner Jean-Paul Sartre screams back that life is nothing but an exercise in randomness. Nothing like a philosophical brouhaha roiling around inside the noggin to ruin what might have otherwise been a decent day. In the end, these thought kerfuffles inevitably lead me to counter the “why me?” conundrum with its other half, “why not me?”. This seems to temporarily satisfy both Siddhartha and Sartre, forcing them each to retreat back to their own little corners of my mind, where the Buddha sits in quiet meditation and Sartre drinks and smokes his brains out.

I have of late been giving more thought to the “how’s” of my illness, as in “how the frack did I get so sick!?!?”. Whereas the “why” question deals more with the metaphysics of the situation, the “how” is focused more on the nuts and bolts of the disease mechanism and the circumstances that led to my getting ground-up in its gears. At first glance the “how” might seem as insoluble a question as the “why”, but by sizing up what we know about the disease and matching it with the circumstances of my own life I think I’ve come up with a reasonably plausible explanation for how I got from point A to point B (and the B stands for “Blechh”).

It’s long been suspected that Multiple Sclerosis and other so-called autoimmune diseases have strong genetic components. As scientists have begun to unravel the human genome, more and more genes have been discovered that seem to play a role in the Multiple Sclerosis disease process (click here and here). While many patients might not be able to isolate their own genetic susceptibility without a complete mapping of their DNA, in my case the genetic connection is actually quite clear.

My mom developed gestational diabetes when she was pregnant with me, and unlike the vast majority of such cases, her illness did not resolve after I was born. Stranger still, her malady turned out to be type I diabetes, otherwise known as juvenile diabetes, by far the most serious form of the disease. Type I diabetes is thought to be caused by an autoimmune attack on the pancreas, leaving it unable to produce insulin. A shake of my mom’s family tree revealed that her grandfather and uncle also had type I diabetes, indicating that there is certainly a genetic trait for the disease being passed down from generation to generation. Research has shown that the children of diabetics have a 50% greater chance than the general population of developing some sort of autoimmune disease, and here I am with not only MS but also Hashimoto’s thyroiditis, an autoimmune disease that destroys the thyroid gland. It is also suspected that I’ve had an autoimmune attack on my pituitary gland, and for a while the doctors thought I had discoid lupus, an autoimmune disease that attacks the skin.

Of course, simply having the genetic predisposition to develop a disease doesn’t on its own guarantee that a person will get sick. Given my family history, it’s likely that many of my relatives share these same funky genes, and none of them, to my knowledge, have developed diabetes, Multiple Sclerosis, or any of the other usual suspects (lupus, rheumatoid arthritis, Crohn’s disease, etc.). Somewhere along the line something needs to trigger the genetic susceptibility for disease to take hold, in effect turning the “sick genes” on. In the case of MS, scientists have long focused on the Epstein-Barr virus (EBV), a member of the herpes virus family, as a likely disease trigger.

Epstein-Barr virus is the nasty bug responsible for mononucleosis, although most people infected with EBV never do develop Mono. Instead, the initial infection can manifest as a severe cold or flu, and a person can often be infected without having any symptoms at all. Once infected with EBV, the virus stays within a patient’s body for the rest of their lives. Infection with Epstein-Barr virus is so common that it’s estimated about 90% of the adult population harbors the virus. Astoundingly, though, it’s been found that 100% of MS patients are infected with EBV. That’s right, 100%. The correlation is so high that some researchers have stated that “people who are not infected with Epstein-Barr virus do not get MS” (click here).

Sure enough, blood tests have revealed that I am indeed infected with EBV. Of course, since the vast majority of adults are also infected with Epstein-Barr virus, the virus alone can’t be the cause of Multiple Sclerosis. In conjunction with a genetic susceptibility, though, the virus may be the thing that tips the scales between health and illness.

It’s interesting to note that in its dormant state, Epstein-Barr virus takes up residence within the immune system’s B cells. Just so happens that some of the MS disease modifying drugs destroy a patient’s B cells, thereby ridding the body of much of its EBV load as well. The interferon drugs (Rebif, Avonex, Betaseron, Plegridy) also happen to be very strong antivirals. Could it be that these drugs work, at least in part, not because of their immunosuppressive or immunomodulating properties, as is commonly believed, but because they are attacking EBV in the bodies of MS patients? Not a mainstream idea to be sure, but something I think worth considering.

Epstein-Barr virus isn’t the only infectious agent that has been linked to MS. The bacteria responsible for many sinus infections have been implicated in the disease as well (click here and here). I’ve suffered from sinus infections most of my life and had endoscopic sinus surgery in 2006 to try to eradicate the problem. Unfortunately, the surgery only helped temporarily, as my sinus problems reemerged soon afterwards. So I’m two for two when it comes to possible infectious triggers for Multiple Sclerosis.

Actually, make that three for three. Exposure to toxic molds and funguses have also been linked to neurologic and demyelinating diseases (click here), and back in the 1990s, when I was living in South Florida, I spent two years working in a building that was found to be riddled with toxic molds and bacteria. At the time I was employed by a startup company, and after a few months working in their very crowded offices the company moved into a larger building that had been empty for quite some time. The facility was in pretty bad shape, with wires dangling out of the decrepit ceiling panels and a musty smell hanging in the air. Simply walking into the place felt unhealthy.

After spending about a year and a half working within those walls it was revealed that upper management had been sitting on an environmental report which stated that the building was riddled with a smorgasbord of toxic microorganisms. The sons of bitches in the executive offices had kept the report hidden until one of their administrative assistants copied it and left it on the desks of several employees. Soon after, men in hazmat suits came and sectioned off parts of the building as they decontaminated the place section by section. In retrospect, my first weird symptoms started cropping up while I worked in that building, and last year when I was tested for exposure to toxic molds the results came back positive. Wonderful.

Stress is another factor that has been linked to MS and similar diseases. Many MS patients report their first symptoms after periods of acute stress, and it’s been demonstrated that stress can bring on relapses in those patients suffering from Relapsing Remitting Multiple Sclerosis (click here). Though I’d always been neurotic and prone to worry, my years in South Florida were especially filled with stress, both of the acute type brought on by upsetting life events, and long-term simmering stress engendered by living in a place where I always felt like a stranger in a strange land.

My periods of acute stress were almost always initiated by the breakup of romantic relationships, which I inevitably took much harder than was even remotely reasonable. Losing a long-term girlfriend more often than not sent me into a period of prolonged psychological agony, during which I’d lose weight, sleep, and sense of self for months and months at a time. Yes, I know it’s hard to believe that any woman would leave a fella as oozing with charm as me, but lo and behold, there were a few who unceremoniously gave me the gate. And when they did, I imploded. Seems I had an incredible knack for zeroing in on precisely the women who would be most toxic to me and then fall for them, hard. I believe the accepted psychological term for a person who habitually engages in such behavior is “jackass”.

Soon after one breakup in 1997 I suffered from incredibly severe headaches for about three weeks, super intense searing headaches that emanated from the base of my skull and left me damn near completely debilitated. Now my MRI images reveal my one big juicy MS lesion at the very top of my spine right beneath my brainstem, precisely at the spot from which those headaches seemed to radiate. Could it be that those headaches of old were somehow involved in the formation of the lesion that is at the root of my current neurological mess?

The latter five or six years of my stay in South Florida found me enmeshed in a kind of simmering, low-level stress brought on by trying to be someone I wasn’t. I spent that time working in extremely corporate environments, shirt and tie type places that I found to be soul stifling. Though I had creative jobs within those organizations, the stress of trying to conform with corporate culture took its toll. I had once sworn I would never join the 9-to-5 workaday world, but there I was, sending myself off to prison each and every day.

Though I made several very close friends in Florida and was never wanting for a social life, I always felt somewhat alien there, my aesthetics and values simply at odds with the place and most of its inhabitants. Still, for reasons I can’t fully explain, I remained living in a place I couldn’t stand while working at jobs I hated until one final romantic breakup mercifully sent me packing back to New York, where I rediscovered the me that I’d almost forgotten existed. And then, just a few years later, the beast that had been showing glimpses of itself for years finally reared its ugly head, and I was diagnosed with MS.

There then is the “how” of my disease, as best as I can figure. Genetic predisposition? Check. Exposure to infectious triggers? Check. Periods of stress, both acute and long-term? Check. Now, if only there was some way to uncheck some of those boxes. Researchers are just starting to try to figure out how to address the genetic aspects of disease, and many biotech startups are attempting to develop gene therapies for a variety of illnesses. Scientists are working on vaccines for Epstein-Barr virus, but the work still seems to be in its early stages (click here). And though life will never be free of stress, individuals can learn techniques such as mindfulness and meditation that can help them make better life choices and reduce the impact of stress on their existence.

I wish I could say that figuring out how I got sick brings with it some sort of gratification. I suppose that on a purely intellectual level fitting the puzzle pieces together into a somewhat coherent picture is a teensy weensy bit satisfying. Then again, all of my conjecture may be completely wrong, my illness due more to the evil eye put on me by a Gypsy beggar I once crossed than to the elements identified by my keen analytical powers. Perhaps it was my destiny to wind up the Wheelchair Kamikaze, and no matter what choices I made, all roads would’ve converged at point B (as in B, for “Barf”). Okay, I’d better stop this thought train before Siddhartha and Sartre square off and pelt each other with rocks and garbage in the deepest recesses of my brain pan…