Wednesday, February 10, 2016


Allow me to apologize in advance for the contents of this essay. Quite simply, I’m fed up with Multiple Sclerosis and everything that has to do with Multiple Sclerosis. Those expecting to find any form of eloquence, wisdom, inspiration, or other redeeming qualities in these words will probably be sorely disappointed. Like a bulimic who just polished off a giant platter of lasagna, I’m feeling the need to purge and I have a hunch the results won’t be pretty. What follows promises to be more of a free-form rant than well-constructed discourse. I can’t guarantee any kind of narrative flow or grammatical cohesion, much less literary flourish or clever turn of phrase. No, instead I’m just gonna let it rip, an unadulterated regurgitation of everything about MS that’s been stuck in my craw these last few months. This may not be for the faint of heart, as I just might wander into some very uncomfortable territory. Okay, you’ve been warned; now’s the time to either buckle up or head for the exits.

MULTIPLE SCLEROSIS SUCKS!!! I hate this fracking disease. I hate what it’s doing to me, I hate what it’s doing to my MS friends, I hate what it’s doing to those who love or even barely put up with me. I hate the creeping paralysis, I hate the spasticity, I hate the pain, I hate the spasms, and I hate the unrelenting, soul crushing march of constant progression. I hate the slow, systematic dismantling of the life I used to know, I hate the steady erosion of everything I once thought of as “normal”, I hate the constant flow of indignities large and small handed out by the disease. I hate the word “multiple”, and I hate the word “sclerosis”.

I’m sick of being sick, and I’m sick of being sick of being sick. I’m tired of being tired, and I’m tired of being tired of being tired. I’m aghast at the fact that the balance between body parts that work and body parts that don’t work is starting to tip heavily in the favor of “don’t work”, like a sinking ship rearing up as it gets ready to make its fateful plunge. The list of things I can’t do are starting to outnumber the list of things I can do, despite the constant physical and mental adjustments and gyrations that I make trying to contort my life to fit within the ever constricting boundaries imposed by this hellacious disease. I find it impossible to ever get used to having this curse; at least three times a day I find myself shocked at my predicament, barely able to fathom that this is actually my life.

As of this writing I can barely dress myself, can’t cut my own food, can take but one or two hideously painful and treacherous steps accompanied by the gruesome sounds of the crunching and cracking of my hip bones literally so loud that they can be heard across a large room, courtesy a tortuously painful degenerative bone condition brought on by IV steroids that were supposed to help curb this monster. I can only sleep in one and a half or two-hour spurts because of the insane pain in my hips and shoulders, and on most days I barely have the stamina to spend more than three or four hours at a time out of bed. My right arm is emaciated and most often bent at the elbow due to spasticity, my right leg as weak as a noodle. The left side that I've come so much to depend on is well on its way to failing, the thought of which bores a hole through my very being. And then there are the “bowel and bladder issues” that I share with so many other MSers. Such polite terminology for the fact that we can barely crap and can’t stop peeing. And despite this litany of dysfunction, I know that I’m still one of the lucky ones, as so many with this scourge are in far worse shape than I.

I’m fed up with well-meaning folks uttering some of the stupidest things I’ve ever heard in an attempt to make themselves and me feel better. Upon learning of just why it is that the right side of my body is a shriveled mess and my ass is stuck in a wheelchair, one woman cheerily informed me that her best friend’s husband is completely bedridden due to Progressive Multiple Sclerosis, but that he was just about the happiest person she knows. I just sat there smiling and nodding my head, while on the inside wishing that a rogue chimpanzee would suddenly materialize and eat her face. Her best friend’s bedridden husband is just about the happiest person she knows? A man who could very well be totally paralyzed, completely incontinent, and probably has to use a feeding tube for nourishment? And this poor soul is just about the happiest person she knows? Remind me never to accept an invitation to a dinner party at her place, I’d probably have more fun socializing in a mausoleum.

I’m angry that the most insidious and destructive form of the disease, Progressive Multiple Sclerosis, the form I suffer from, is kept hidden from public view like a Victorian era mentally deficient child kept locked in an attic. Courtesy the mainstream media and the Multiple Sclerosis Societies, the public never sees the ravaged bodies and mangled lives of people hit hardest by the disease. Instead, the face of MS belongs to celebrities and those patients left mostly unscathed by the illness. There’s even a TV commercial for an MS drug, Tecfidera, that portrays the disease as quite literally something of a carnival. Funny how those celebrities with MS whose disease takes a turn for the worse fall from public view, isn’t it? Where are you, Terry Garr?

Progressive Multiple Sclerosis has made me envious and prone to jealousy, not only of healthy people but even of people with other illnesses. I’ll confess that this even includes people suffering from the relapsing remitting form of the disease, even though I know that RRMS can be its own particular form of hell and can eventually lead to Progressive MS. But just the idea of a remission, a break from the never ending grind of watching myself slowly disappear seems absolutely heavenly. At this point I think I’d give up all the remaining years of my life for just a week of normalcy. Hell, maybe even just an hour. Sixty minutes to go for a walk, to run and jump and dance and button my shirt and tie my shoe and hug my wife and – gasp – drive a car! Yeah, sign me up. That would be one heck of an hour.

Along those same lines, here’s an even more disturbing confession. In ruminating through mental lists of diseases that might be worse than Progressive MS (leprosy, for instance), I sometimes find myself thinking that cancer would be preferable to this creeping paralysis. I know, heresy. But as undeniably horrible as is cancer, at least it’s a disease that ultimately and in relatively short order comes to some sort of conclusion. Yes, I’m fully aware that the disease puts its victims through living hell, and that cancer treatments often seem worse than the disease itself, but at least there are treatments. And at the end of those treatments patients either beat the disease and become survivors who can then begin to reassemble the shards of their life, or they die. Progressive MS doesn’t have the good manners to finish off its victims, instead leaving its least fortunate sufferers consigned to live out their years as fully conscious brains trapped inside prisons of completely useless flesh and bone. The stuff of horror movies, a fate far worse than death as far as I’m concerned. Progressive MS has exorcised me of any fear of death. In fact, given the aforementioned almost unthinkable but quite possible outcome, on many days I’m far more afraid of living than dying.

I'm aware that to many the above words may seem shocking and wrongheaded, but there’s a reason that MS was second only to cancer among the ills suffered by the patients that the infamous Dr. Kevorkian helped end their lives. Okay, hell, now that I’ve stuck my toe into these murky waters I might as well dive all the way and speak about what goes largely unspoken, at least to those outside of the Progressive MS club. Any number of studies suggest that suicide be listed among the consequences of Multiple Sclerosis, since so many late stage MSers decide to take matters into their own hands. In my many conversations with other people with Progressive MS, I’ve found that most have formulated some sort of escape plan, some in only vague terms but others down to the last detail.

Anybody who would condemn folks for having such thoughts need to keenly consider the gaping abyss people with advancing Progressive MS stare into on a daily basis as their thus far untreatable disease drags them ever forward towards the dark at the end of the tunnel. The relief expressed at finally being able to give voice to such taboo thoughts is just about universal among those I’ve communicated with, and is cathartic in its own right. Almost never shared with outsiders, most of the people who have related their thoughts and plans with me find them not self-defeating but rather self-empowering, bracing them to suck it up and fight on secure in the knowledge that if the fight becomes just too brutal and the climb to steep they’ve given themselves permission to call it a life. And in that there is no shame.

Let me assure all concerned that I’m not suicidal. I’m too damned angry to be suicidal. I’ve so far taken all of the wallops that this disease has meted out and found ways to fight back, and though I’m afraid I’ve not managed to land many blows on my disease itself, I take comfort in the knowledge that I may have in some tiny way helped a few of fellow travelers on this torturous path to better navigate it by sharing the load even as I unburden myself on these pages. One of my oldest friends long ago described me as the most optimistic pessimist he’d ever met. I guess it’s this odd emotional mix that helps keep me going, half expecting that this hair-raising downward trajectory that has me in its grip will ultimately turn out to be a ski jump, and in the end the momentum gathered during this freefall will be transformed into escape velocity, allowing me to soar higher than I ever imagined.

Yeah, wishful thinking perhaps, but on the day of my diagnosis I vowed that if this disease was going to bring me down I was going to go down with all guns blazing, fists bloodied and mouth spewing venom. And should this descent turn out not to be the launchpad of my fantasies, if I ever do decide to pull the ripcord, let that act not be viewed as defeat but rather a final kick to the nuts of the monster. Stay strong, my friends; together we may not beat this horror, but we’ll damn well keep on trying.

Monday, January 18, 2016

An Interview with Dr. Saud Sadiq – FDA Approves Phase II MS Stem Cell Study Conducted by Tisch Research Center of New York

In some dramatic news regarding stem cell treatments for Multiple Sclerosis, the FDA has given its first ever approval for a Phase II Multiple Sclerosis regenerative stem cell trial to the Tisch MS Research Center of New York.

Most previous attempts at using stem cells to repair MS damage have involved intravenously infusing a basic type of stem cell (called mesenchymal stem cells) back into the patient from which they were taken. The Tisch Center (click here) takes this approach several steps further, using proprietary methods to transform raw mesenchymal stem cells into a type of stem cell known as neural progenitors, which are specific to the central nervous system. The cells are then injected directly into the spinal fluid of trial subjects, where, in theory, they should be more effective than raw mesenchymal stem cells at effecting repairs and combating the disease. The Phase I results of the Tisch center’s trial thus far have been quite impressive, offering MS patients worldwide a glimpse into the future of MS treatments and some tangible reasons for hope.

A press release put out by the Tisch Center provides details on what has already been accomplished in the Phase I trial, and what is being planned for the upcoming Phase II study:

"Our unprecedented Phase I results have propelled us into the next phase of research," said Dr. Saud A. Sadiq, Chief Research Scientist at Tisch MSRCNY and the study's principal investigator. He added, "No treatment has shown reversal of established disability until now. The objective improvement experienced in bladder function, vision and walking speed in both secondary and primary progressive MS is remarkable. We now plan to establish efficacy of stem cells as a reparative therapy in Phase II."

The Phase II trial will be a double-blind, placebo-controlled, randomized trial with forty patients in a crossover design. Stem cells are taken from the patient’s bone marrow and manipulated to become brain-like neural cells, a process created and found only at Tisch MSRCNY.  All treatments and research will be conducted at the Tisch MS Research Center of New York and will expand to include an additional leading MS center.

The main obstacle in intiating the study is the need for critical funding. Once funding is obtained, patients will be recruited and the study is anticipated to commence in the summer of 2016.

I had the chance to talk with Dr. Sadiq (who just so happens to be my MS neurologist) about this ongoing and groundbreaking MS stem cell trial, as well as other stem cell related topics. The following interview has been lightly edited for clarity…

How long did it take the Tisch Center laboratories to develop the proprietary process to produce neural progenitor cells from raw mesenchymal stem cells?

Dr. Sadiq: It took about 2 ½ years of intensive lab work, and our lab is the only lab in the world currently using this process.

Is this type of stem cell treatment considered a cure, or can patients expect to require repeated treatments in order to maintain whatever benefits they achieve?

Dr. Sadiq: All of this is still in the experimental phases, so we really don’t know how long the treatments will need to be continued in order to maintain benefit. It’s likely there will be an initial induction period where we will do a number of frequent treatments to induce repair and then to maintain the benefits I think it will require less frequent treatments. But I anticipate that some treatments will need to be given for the duration of the illness, until we find the cure.

What was the treatment protocol during the Phase I trial, and what will the treatment protocol be during the Phase II trial?

Dr. Sadiq: In Phase I we did three treatments over the course of one year, which seemed necessary in order to get some benefit. We don’t know whether the Phase I patients will continue to show benefit or not without further treatment. In the Phase II trial, we are proposing six treatments over a year followed by no treatments over a year to see if benefits are sustained. There will be a control group as well, who will get no treatments the first year and then get six treatments the second year. I anticipate less frequent treatments will be needed to maintain benefit for the duration of the disease until we find a cure.

And would this hold true for any type of regenerative stem cell treatment, such as those being offered by some of the for-profit clinics at which many patients are seeking a single treatment or a single round of treatments over a relatively short period of time?

Dr. Sadiq: Most likely yes, it’s been shown that one treatment probably would be insufficient to even start regeneration. You’ll need multiple treatments…

Are the effects of the regenerative stem cell treatments cumulative?

Dr. Sadiq: You know, we don’t know that yet, in the Phase II trial we intend to collect data on this question…

How much more effective are the neural progenitor cells than the raw mesenchymal stem cells (MSCs) that have been used in other trials?

Dr. Sadiq: Well, as far as I’m aware, the way MSCs have been used in trials so far, there’s not been a single trial that has shown real substantial benefit with MSCs. There’s been some very mild improvements seen in the Cambridge trials, which used one dose given intravenously. It could be that they didn’t use fresh cells or they didn’t use the proper route of administration. Our trial administers the cells intrathecally, directly into the spinal canal. It could be that raw MSCs are in fact effective, but the trials I’ve seen didn’t use multiple dosing. So it’s very difficult to compare the two. But in our hands we found that neural progenitor cells given intrathecally are more effective than raw MSCs.

How much funding is needed for the Phase II trial?

Dr. Sadiq: For the Phase II trial alone we need about $3 million, but for the actual support that we need to build out and expand the labs I’m looking to get $10 million. We need expanded lab facilities and an animal testing facility in place to properly conduct the Phase II trials.

And how much money have you already raised?

Dr. Sadiq: Planning for Phase II we just started, so we haven’t raised anything yet. We have talked to the National Multiple Sclerosis Society, we’ve talked to the National Institutes of Health. We are submitting a grant proposal to the NIH, and the MS Society Is in consultation with me currently to try to arrange funding. We’ll will have to apply for funding grant from the NMSS. We do have a pledge of about $3 million from one donor.

Wow, you have a pledge of $3 million from one donor?

Dr. Sadiq: Yes.

Is the Phase II trial on hold until all of the funding is in place?

Dr. Sadiq: The trial is not on hold, we are really just starting to think about implementation. We just received FDA approval, and we are going to get another MS center involved, I’m in talks with another MS center here in New York, and then after they’re on board we will get things going. So even if we got all the funding right now, we wouldn’t be able to start the trial until late summer 2016. Right now were planning on starting the trial in July or August 2016.

Assuming everything goes as planned, and there aren’t any unforeseen problems, how long do you think it would be until the type of treatment you are trialing would reach common clinical practice?

Dr. Sadiq: It will probably be by the end of the decade, by 2020 I hope if everything goes well.

Do you think there’s any difference in effectiveness between bone marrow derived and adipose (fat cell) derived stem cells?

Dr. Sadiq: Well, we’re not sure. We started working with bone marrow derived cells from the beginning, but adipose derived may turn out to be better because adipose tissues contain a greater number of MSCs, so you may be able to get a better harvest. But because the FDA oversees every project from start to finish, and our trials began using bone marrow derived cells, if we started using adipose cells now we have to go back to the drawing board with the FDA. So in order to continue our ongoing trial protocols, since we started with bone marrow derived cells, we will continue using bone marrow derived cells.

Do you have any thoughts on the clinics that are currently doing mini liposuctions and then re-injecting the cells intravenously the same day or the day after?

Dr. Sadiq: These clinics are just using the stromal fraction, and nobody really knows what that achieves. This process is really not a stem cell therapy, since the stromal fraction only includes a small number of MSCs. It seems like these clinics just want to make money, there’s no evidence that this method would be effective, at least when dealing with neurodegeneration.

What other avenues of research are being pursued in the Tisch MS center’s labs that you consider most promising?

Dr. Sadiq: My goal in life is to find the cause of MS, and that’s really where I concentrate my efforts. I think we have a number of discoveries that are coming together now and I hope that one day soon we will be able to declare that we’ve found the cause of MS.

We do a lot of work with biomarkers as well. In this Phase II trial we are going to look at all the biomarkers that are associated with clinical response, to be able to identify a marker that will be able to predict which patients have the best chance of responding and seeing benefit, and through what mechanisms they are getting better. This is very important work but it’s not the work that drives me to come into the clinic every day at 4 AM.

What does drive you to come to work every day at four in the morning?

Dr. Sadiq: That’s to find the cure to this damned disease.

I can personally attest to Dr. Sadiq’s obsession with finding the cause of and cure for MS. Through the years, Dr. Sadiq and I have developed quite a strong bond, and I know from experience that he can be found hard at work in his clinic and laboratory nearly round the clock, very often at least six days a week. I’ve spoken to Dr. Sadiq via telephone at all hours of the day and night, and have even had office visits with him on the day after Christmas. He once showed up at my bedside at 3 AM when I was hospitalized and suffering miserably from MS related symptoms, to simply be there with me and literally hold my hand. Not your typical doctor, to be sure.

As Dr. Sadiq makes clear, funding is of the utmost importance in order to get this trial up and running in as timely a fashion as possible. There is a tremendous amount of work to be done, and all donations, no matter how small, will make a difference.

As a long-suffering MS patient myself, I know that friends and family are often eager for ways to help fight the disease. While there are many worthy MS charities, in my opinion the biggest bang for the MS donation buck can be had by donating to the Tisch MS Research Center of New York. Donations to the Tisch Center will directly serve to hasten the completion of these stem cell trials and hopefully bring this exciting technology to MS patients worldwide. Please pass the word along, and (click here) to donate.

A big thank you to all who participate in and contribute to this project, and to all the Wheelchair Kamikaze readers that have made their voices heard at the NMSS in regard to funding the Tisch Center’s efforts. It appears that the MS Society may finally be ready to listen, and hopefully the NMSS will this time come through with funding for this vital research.

I’ll keep you posted…

Friday, January 8, 2016

New Year's Eve Through MS Eyes

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 with a lusty 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 soirĂ©es 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 forever 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 had 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 long in the tooth black and white console TV. We didn’t have much money and lived in a building in the Bronx that was closer to tenement than 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 somehow defiantly low rent 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 got older, as a young adult I fully embrace the revelry of the holiday. I had quite a few memorable New Year’s Eves, 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. 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 good 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 one’s 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 voice, “Happy New Year’s!”…

Here's some wonderful old footage of a Guy Lombardo ushering in New Year's Eve in 1957, a few years before my time…

Tuesday, December 15, 2015

Creeping Paralysis

Back before the words Multiple Sclerosis entered the general lexicon, the disease, especially in its progressive forms, was commonly called Creeping Paralysis. A quick Internet search through the archives of the New York Times reveals the term being used on quite a few occasions dating back to the 1870s (when the archived materials begin), most often and quite disconcertingly within the text of an obituary. A typical example is the 1886 obit of a Mr. Benjamin Moran, an American diplomat stationed in London who was apparently quite the bon vivant, a “great society haunter” who was “smart, lively, and amusing” (click here to download a PDF of the obituary). As described in Mr. Moran’s written memorial, “For the last few years he was a dreadful sufferer of Creeping Paralysis, which rendered him completely helpless…”. Sigh.

Of course, we can’t be sure that Benjamin Moran suffered from Multiple Sclerosis, as Creeping Paralysis is an apt label for any number of similar maladies, such as ALS (Lou Gehrig’s disease), or advanced spinal stenosis. Still, Creeping Paralysis is a terrific descriptor of the effects of Progressive MS, so much so that I’ve often used the phrase here on these pages, and I’ve considered wielding it as an answer when people wonder out loud just why my backside is stuck in a wheelchair. “Creeping Paralysis” would certainly quench their curiosity more effectively, I would think, than the clunky and hard to decipher answer that I currently employ, “Progressive Multiple Sclerosis”. There is much confusion about just what the hell Progressive Multiple Sclerosis is, even among people with Multiple Sclerosis. Progressive Multiple Sclerosis sounds like some kind of politically left leaning version of the disease, whereby Creeping Paralysis sums up the disease and its perils in two easy to understand words, very clear and concise. “I have Creeping Paralysis”. Conversation over.

Unlike Relapsing Remitting MS, whose torments come in the form of acute attacks that eventually recede, sometimes leaving residual symptoms in their wake, Progressive MS is the gift that keeps on giving, inflicting a slow, steady decline in function leading to ever increasing disability over time. In other words, Creeping Paralysis. Mine first crept up in 2003 as a slight buckling of my right knee that only surfaced after I had walked several miles. I’d experienced any number of weird symptoms for years before, but it was the knee that finally sent me to the doctor. Over the next weeks and months, that initial problem spread to ever-increasing weakness invading my entire right side, insidiously creeping through my right leg, arm, and hand. Three years post diagnosis I needed an ankle brace to keep my right foot from dragging along the ground when I walked, year four saw me using a cane, and in 2008, five years after I’d been slapped with the MS label, my Creeping Paralysis had done enough damage to insist that I use a mechanical throne for ambulation.

Creeping Paralysis treats each of those it abuses differently. I know some folks who have had the disease for decades and are still walking, while others find themselves bedridden within 10 years, sometimes sooner. Generally, the disease treats women more gently than men, although, unlike Relapsing Remitting MS, which victimizes women far more often than men, Progressive MS attacks men and women in equal numbers. While there are currently about a dozen approved treatments (however imperfect they may be) that can help keep the worst ravages of Relapsing Remitting MS at bay, at present there are no treatments that have proven to be effective in even slowing down Progressive MS for the vast majority of the people it attacks.

During my first five years with the disease, the paralysis I experienced felt less like it was creeping and more like it was blitzing through my body like the Nazi armies crashing through Belgium on their way to overtaking a completely underprepared, overwhelmed, and horrified France. Five years may sound like a long time, but when those years see you diminished from fully functional to wheelchair reliant and from working to “on disability” they seem like the blink of an eye.

For many years my Creeping Paralysis was confined almost exclusively to my right side, leaving my left largely untouched, allowing me the hope that this would continue to remain the case and that I’d retain a fully functional left arm and leg, a situation I wasn’t happy about but with which I could make do. ‘Twas not to be, however, as whatever obstacles had kept the creeping temporarily restrained to one hemisphere of my body fell by the wayside, and for the last several years the paralysis has assaulted my right side as well, increasingly taking hold. Despite all efforts – and the list of those efforts is incredibly long and varied – my Creeping Paralysis has yet to meet its Waterloo (yeah, yeah, I know I’m mixing up my military metaphors, so sue me).

Increasingly, I’m finding that Creeping Paralysis is impacting not only my body, but my mind and spirit as well. As the disease has become more and more entrenched, and my body less and less able, I suppose it’s inevitable that the condition takes a psychological toll. I’ve learned that paralysis can extend beyond the physical realm. The bodily restrictions imposed by the disease are increasingly accompanied by a psychological reticence to test the boundaries defined by those restrictions; it’s far easier and much less disheartening to curtail activities that once gave me pleasure rather than find out for sure that I can no longer do them. Thus my old hobbies of shooting videos and taking photos from a camera mounted on my wheelchair have fallen by the wayside, my camera equipment gathering dust for the last 18 months or so, it too victimized by my Creeping Paralysis. The ever less dexterous fingers on my one working hand can’t properly control my camera and lenses, and my last attempts at photography proved to be nothing but exercises in frustration.

When simply getting dressed pushes the limits of what is physically possible, the prospect of committing to social activities becomes daunting. Healthy folks seem to have a hard time understanding this. After all, just a few years ago I was out in my wheelchair meeting them for lunch on a regular basis. Thus, despite my best intentions, Creeping Paralysis has frozen not only some of my body parts but some of my relationships as well. I can’t blame friends and family for drifting away in the wake of unreturned phone calls and unanswered emails, but I try not to blame myself, either. In addition to Creeping Paralysis, I have also to deal with widespread endocrine dysfunction and a hideously painful degenerative bone condition, and at times even when there is a willingness to interact, the effort required for lively conversation or the composition of a lucid note can be simply too much to muster. Creeping Paralysis seems to rejoice in imposing limitations on all aspects of life.

There’s a fine line between capitulating to the disease and adjusting to its ever-changing realities. I have found the that less I am able to do the less I am interested in doing. Being out and about in the healthy world, among all of the obliviously fortunate people whose limbs perform seemingly miraculous feats without any apparent effort – like walking or using a knife and fork – can offer much-needed distraction, but can also place a laserlike focus on all that I’ve lost, almost mocking me for those losses. Even watching television can become a seriocomic affair, as commercial after commercial advertises products that are no longer of any use to me, hawking them to a population of which I am no longer part. Cars, exercise machines, the latest electronic wonders, items that in some long-ago life might’ve piqued my intense interest now serve only to illuminate the ugly metamorphosis I'm experiencing courtesy Creeping Paralysis.

Despite the at times dour tenor of this essay, please know that through it all I still laugh far more than I cry, still strive to find nuggets of joy wherever I can, even if I have to dig through piles of manure to get at them. I’m fighting the many components of my disease as hard if not harder than ever. Earlier today my wife and I chuckled as we marveled over the fact that I’m taking medicines in pretty much every way they can be taken. I’m inhaling aerosolized antifungal medication to treat a potential mold infection in my sinuses; getting injections of testosterone as part of my fight against my endocrine issues, ingesting antimicrobial drops and liquid probiotic cocktails in an effort to rebalance my gut Microbiome, getting an intravenous treatment called plasmapheresis in an attempt to beat back the Creeping Paralysis, and taking pills by the dozen. We concluded that the only mode of drug delivery I’ve missed is anal suppository. I’ll have to get hard at work on that one. Not.

So there you have it, Creeping Paralysis and my experiences with it. Hopefully, with an assist from modern medicine, I’ll ultimately fare better with the disease than the unfortunate Mr. Benjamin Moran, whose obituary I highlighted earlier. Somehow, calling my illness Creeping Paralysis rather than its more modern and scientific name gives me some strange sense of satisfaction. No beating around the bush with a name like Creeping Paralysis, it presents the illness in all its stark reality. Using a term as impenetrable as Progressive Multiple Sclerosis in some ways insulates those involved from confronting directly the potential horrors of the disease, a trick at which modern medical nomenclature excels. I’d rather stare this bastard right in the eyes and call it what it is: Creeping Paralysis, a name as ugly as the disease itself.

Oh, if anybody can shed any light on "the culture of the jumping cat" that is mentioned in Benjamin Moran's obituary, I would be forever grateful. Again, you can download the obituary by (clicking here). I'd just love to know what was meant in the 1880s by "the culture of the jumping cat", but can find no reference to it anyplace else. Please leave any ideas in the comments section of this post.

Monday, November 23, 2015

Bits and Pieces: MS Diversions

Wow, I just checked and it’s been almost 7 months since I last did a “Bits and Pieces” post. These posts, compendiums of the latest and greatest MS news and info, have long been a regular feature on these pages. Somehow, I’ve really let things slide. Seems I’ve been a very naughty blogger. The blogging police are probably getting ready to mount a raid on my computer any day now, so I better get back on the beam, lest I be found guilty of blogging negligence and sentenced to reading the comments section of some celebrity gossip website until my brown eyes turn blue. For the record, Justin Bieber is NOT hotter than ANY of the guys in One Direction and anyone who thinks so is a big fat stupid loser!!!!! And the budding romance between Gwen and Blake is like the best thing that ever happened in the world ever ever ever!!!! I might have to cut down on watching of kitten videos so I can soak up every word being written about those two crazy love birds. OMG.

Just to refresh everybody’s memory, Bits and Pieces posts are collections of interesting items of MS related research, news, and other Internet MS flotsam and jetsam that have caught my attention in the recent past. Though there’s certainly been plenty of impactful MS info floating around the inter-webs during my long lapse in trying to anthologize it, I made the command decision to devote this post to a collection of MS related online communities, blogs, and other sites that I think might be of interest, places which can serve as welcome diversions in the online MS world. Personally, I can sometimes get so caught up in parsing through all the latest research that I neglect the touchy-feely human side of things. The sites that follow offer interesting twists on typical online forums, blogs, and whatnot. Especially the whatnot, along with the doohickeys and thingamajigs.

Please note, I know there are lots and lots of MS themed blogs and communities out there, and by calling attention to these few I don’t mean to slight any of the others. This isn’t a “best of” list, just a compendium of places that have stuck in my brain pan lately. So, without any further hemming and/or hawing, here are some suggested sites upon which to aim your eyeballs…

♦ Let’s start with a site that has long been near and dear to my heart, MS Kurmudgeons Korner (click here). MSKK, as it is affectionately known by its regulars, is an under the radar MS forum that is completely beyond the reach of any Internet search engines, making it accessible only to those in the know. The site adheres to a strict privacy policy, meaning that what is said in MSKK stays in MSKK upon pain of death. MS Kurmudgeons Korner is so named because it is a self-avowed rainbow and unicorn free zone where people are free to discuss the fact that MS sucks huge hairy monkey balls without fear of stepping on anybody's rose-colored glasses. Not that the place is without humor, as at it's often more fun than a night at the GiggleSnort motel, but it is definitely Nowheresville for those prone to utterances like “I have MS but MS doesn’t have me”.

Since MSKK is a closed community, it’s rare that the gates are thrown open in such a public fashion as this. However, due to the usual ebb and flow of the Internet, membership is down and an infusion of new blood will be welcomed. In all honesty, because of the progression of my illness and the incredible amount of time it takes just being sick (dammit), I haven’t been hanging out there nearly as much as I have in the past, but I guess that’s part of that whole ebb and flow thing.

So, if you are an MS cranky pants with a sense of humor, by all means mosey on up to MS Kurmudgeons Korner and knock on the door. You’ll be asked to sign a virtual privacy policy, and then introduce yourself with an opening post. Current members will then say hello and ask a few questions so that you can get a feel for them and them for you. After you tell a little something about yourself and prove that you’re not an undercover unicorn, you’ll soon be given free rein to join the community.

♦ Next up is a blog called Tripping on Air (click here), which is exceptionally well written by a classically trained singer with MS who lives in Toronto. The writer of Tripping on Air manages to blend her sardonic wit, keen sense of the absurd, and terrific observational skills into essays on everything from miracle cures to wetting the bed (click here) that have me laughing out loud and nodding in agreement, even though she sometimes talks about girly stuff that doesn’t quite jibe with my manly universe filled with bad zombie flicks and the Boston Red Sox. The blog’s only been around for about five months, so there’s not a huge amount of content, but what is there is well worth a look.

♦ My Counterpane (click here) takes a unique approach to building an online MS community. The site is built around members’ moods, as expressed by “moodifiers”, entries describing a person’s mood and what’s making them feel that way. What really sets this site apart is the ability for members to include videos in their moodifiers, so lots of folks choose to express themselves via short video clips rather than the written word. This all probably sounds kinda weird, but it’s actually pretty engaging. Posts can be sorted by mood, so whether you’re feeling angry or hopeful it’s easy to find others experiencing similar emotions, and members can build a little moodifier universes of their very own by following other members.

I personally feel much more comfortable behind the camera than in front of it, but the ability to just sit at of your WebCam and describe whatever emotions life and MS happen to be throwing at you at any particular moment does have its appeal. Unfortunately, these days I’m afraid I often look like one of the zombies in those bad flicks I love so much, and my WebCam would scurry off in horror if I ever turned it on when I’m in such a state. Good thing Rick from The Walking Dead hasn’t chanced upon me, otherwise I’d definitely have a knife sticking out of my head. Still, just having the option to communicate by video makes My Counterpane unique, and that in combination with its mood-centric emphasis has lots of people hooked.

♦ One of the most visually appealing MS blogs I’ve come across is Wheels & Red (click here), put together by an MSer in the Pacific Northwest who goes by the moniker "Wheels" (his wife is “Red”). Wheels (real name Kellen) was diagnosed in 2010 with progressive MS at the age of 25. His wife Meg is a photographer, and a quite talented one at that. Kellen is a very good writer, and his subject matter diverse. Now on full-time disability, Kellen uses his enforced freedom to explore his inner and outer worlds, and presents his viewers with an always interesting hodgepodge of visuals and essays that are both thought-provoking and entertaining.

The only thing I don’t like about Wheels & Red is that it makes me feel old. The writer and his wife are young and Bohemian in a very Pacific Northwest kind of way. Problem is that I’m now a 52-year-old fuddy-duddy who used live a Bohemian existence myself, back before our culture turned a generation of pierced and tattooed twentysomethings into a marketing demographic. My friends and I were slackers about a decade before slacking was a recognized social phenomenon (I believe the term was first brought into mainstream consciousness with the 1991 film “Slacker”). Wheels & Red reminds me of a time before I capitulated and allowed myself to slide down the slippery slope towards 9-to-5 normalcy – for a time I even wore a tie to work every day. Ack! Now, despite the fact that my own disease enforced freedom has returned me to a warped version of the slacker lifestyle, I still rue the fact that regardless of my loud and boasting youthful protestations that I would do no such thing, I sold out. And rather cheaply, at that.

Wow, where did that bit of existential angst come from? I guess a really good blog can do that to you, get your thought processes shooting off on unexpected tangential extracurricular activities, which I suppose is one of the great benefits of any successful creative effort. So, I guess the above paragraph marks Wheels & Red a success. Hopefully, whatever tangents it sends you off on won’t involve self chastisements decades in the making. May all your tangents be happy ones…

♦ Shift MS (click here) is a growing social network for MSers, founded by a young man in England with MS as a way of building connections with others who share the diagnosis. The site is very well put together, with lots of interesting features including a members’ forum, a variety of online groups to join, plenty of MS research info (including a large library of video interviews with MS researchers), and advice on lifestyle and medication choices. The site is pretty slick, so slick that at first I suspected it must have been created by one of the pharmaceutical companies as an undercover effort to collect valuable data on MS patients (I’m not being paranoid; some of the most popular MS and health-related websites are actually just such Trojan horses), but upon further investigation I discovered that Shift MS is a registered nonprofit in England, and appears to be run by a bunch of people with MS for the sole purpose of helping other people with MS. How refreshing! In spite of its numerous offerings, which could make for a cumbersome Internet experience, I found Shift MS to be quite easy to navigate and filled with interesting nooks and crannies. The site has a nice international flavor to it, also, with large groups of Brits, Americans, Canadians, and Aussies represented. Nothing like sharing a potentially crippling disease to break down international borders, huh?

♦ For those who eschew talking to real-life human beings and would rather converse with weird web-based artificial MS patients who hardly ever blink and could easily scare young children, do I have a site for you! The Consortium of Multiple Sclerosis Centers (CMSC) has created a bizarre little program called “My MS Conversation”, that you can download by (clicking here). If you are asked to enter a code for downloading, try 54S2. I promise, the program is absolutely safe, at least from a computer virus standpoint, though I can’t guarantee that using it won’t leave emotional scars.

Upon opening the program, you are “greeted” by four virtual animatronic “people” who move like they are inflated with helium and have big perfectly round largely unblinking eyeballs. One of the characters is a “nurse moderator”, and this jolly foursome is eager to engage you in “conversations” about managing multiple sclerosis. As you can see in the screenshot on the right, this is a very inviting bunch, so unnervingly bizarre that you might be fooled into thinking that you are interacting with actual animated virtual MS people, and not MS zombies just waiting for you to get close enough to your computer screen for them to reach out and EAT YOUR BRAINS! Lucky for me I'm hyper aware of the coming zombie apocalypse, and not easily fooled. This program would be better titled "The Limping Dead", except no matter how much I click on them or hover my face dangerously close to the screen just tempting them to reach out and EAT MY BRAINS these MS zombies won't get up off their seats, so I can't tell just how disabled any of them are. They look pretty healthy, though, which must mean that they've tricked plenty of other people into getting close enough to their computer screens for them to reach out and EAT THEIR BRAINS!

The creation of My MS Conversation was partially funded by two pharmaceutical companies, Teva and Mallincrodt. Teva is the manufacturer of Copaxone, the best-selling MS drug which last year brought in $4 billion in revenue. Yes, that’s “billion” with a “B”, which also just so happens to be the first letter in BRAINS! So, as you might guess, most of the “conversations” that the MS zombies engage in have to do with taking disease modifying treatments. But no matter, the entire experience of using the program is so otherworldly that I find it almost impossible to concentrate on anything the animated MS zombies are saying, as all other thoughts in my head are crowded out by one huge “WTF?”. As I might have mentioned before, I have a huge affinity for all things zombie, but this program could be the one exception. Still, I just can’t get myself to delete the damn thing from my computer, as every now and then I find myself clicking on its icon just to make sure I wasn’t imagining it all or that I didn’t conjure up My MS Conversation in a scary dream one night after eating a batch of bad enchiladas. But no, the program always turns out not to be a product of my warped imagination, but instead of somebody else’s. I definitely want no part of whatever enchiladas they were eating. Or were they maybe – EATING BRAINS!?!?

So go ahead, download My MS Conversation. I dare you.

Thursday, November 5, 2015

A Worthy Cause

(For those receiving this via email, the following post contains multiple videos which aren’t available for viewing in email format. To view the videos, please visit the Wheelchair Kamikaze website, by clicking here)

Okay, folks, I’m going to take the liberty of using my virtual soapbox here on Wheelchair Kamikaze to beat the drum for a worthy cause, an outside the box effort to make the lives of the disabled easier and maybe even a bit more joyful. I’ll include a bunch of videos which will help explain this project and the needs it addresses. If a picture is worth a thousand words, then a video must be worth several hundred thousand, and these short clips will save you the rigors of having to read yet another of my seemingly endless polemics.

I present to you the AXS Map project, which is the brainchild of filmmaker and fellow MSer Jason DaSilva. Jason recently won an Emmy for his documentary film When I Walk (click here), an eloquent and touching exploration of his journeys through the world of progressive MS. When I Walk received many well-deserved accolades at film festivals around the world, and was shown on US television as part of the PBS series POV. The film is available for instant viewing on a variety of streaming platforms, including Hudu, Vudu, iTunes, Google Play, and YouTube (click here).

If you haven’t seen the film, I highly recommend it. When I Walk offers an unvarnished portrayal of the realities of life with a chronic progressive disabling disease without dissolving into pathos, and also offers an uplifting love story to boot. There, now I’ve played film critic, testament to the teaching skills of my professors back in film school over 30 years ago. How nice that my degree hasn’t gone completely to waste…

Ah, but I digress. Back to the subject at hand, the AXS Map project (click here), which endeavors to create an online and mobile app based mapping tool that will allow disabled folks to readily identify accessible shops, restaurants, and other establishments in whatever city or neighborhood they happen to find themselves. The project is worldwide in scope, and its efforts to map locales both near and far involve interactive “mapathons”, organized mapping events that can be turned into fun little competitions. AXS Map project funding efforts are currently underway via a Kickstarter crowdfunding campaign intended to turn Jason’s vision into reality (click here). Here’s a video about AXS Map produced by Jason  that fully explains the project.

As most every disabled person can attest, the frustrations involved in simply trying to accomplish even the most mundane errand can often prove daunting and disheartening. Cities like New York, in which Jason and I both reside, are filled with obstacles that can go completely unnoticed by able-bodied folks, but are just about insurmountable to those of using canes, walkers, wheelchairs, or scooters. Here’s a great video Jason did for the New York Times that vividly illustrates the hassles routinely encountered by those whose legs are no longer their primary means of transportation…

Hey, it occurs to me that this would be a great place to dust off one of my old Wheelchair Kamikaze videos, which were the reason this blog got started in the first place. Way back in 2009 Wheelchair Kamikaze was born with the intention of it being a place to park the videos and photos I was shooting for my wheelchair, a spot on the Internet where friends and family could access my self-indulgent little projects. Among these self-indulgences was a video called “Searching for Audrey Hepburn”, in which I take a wheelchair journey through the streets of New York looking for a statue inspired by the late great actress’s indefatigable humanitarian work on behalf of the children of the world. Along the way I encounter quite a number of the obstacles that can make getting around New York in a wheelchair a genuine pain in the ass. Sadly, the friend I mention in the video, who inspired my search for the statue with his boundless affection for Audrey Hepburn, passed away about a year and a half ago. Rest in peace, Sir Brett, and thanks for the smiles…

And just for the heck of it, here’s a video of Jason receiving his Emmy award for When I Walk, which, even if you haven't seen the film, is poignant and touching in its own right…

Please support the AXS Map project, just waiting for your help to get kicked into high gear. If you’re not in a position to make a financial donation, consider organizing or taking part in a mapathon, thereby helping to make life that much easier for people with disabilities. For more info, just visit the AXS Map website (click here). Thanks.

Monday, October 19, 2015

Video: Promising FDA Approved Stem Cell Trial, Repeatedly Rejected for Funding by NMSS, Featured in TV News Segment

The only FDA approved Multiple Sclerosis stem cell trial currently underway in the US was featured last week in “The Big Idea”, a monthly segment seen on the local New York Fox Network affiliate’s evening newscast. The segment features the study’s lead researcher, Dr. Saud Sadiq (full disclosure: he’s my neuro), detailing the trial, and highlights a patient currently enrolled in the study who appears to be benefiting from the treatment.

The stem cell trial is being conducted by the Tisch Multiple Sclerosis Research Center of New York, and utilizes proprietary methodologies unlike those being used in any other stem cell study or treatment center in the world. As is detailed in the below video, raw mesenchymal stem cells are extracted from a patient’s own bone marrow and are then transformed in the laboratory into Neural Progenitor cells, stem cells specific to the central nervous system. The cells are then introduced directly into the patient’s central nervous system via intrathecal injection. Unlike HSCT, the type of stem cell therapy that seeks to stop or slow down MS disease progression by rebooting the immune system after ablating it using chemotherapy drugs, the Tisch Center’s trial is aimed directly at regenerating and restoring the damage done to brain and spinal cord tissues by the MS disease process.

Regular Wheelchair Kamikaze readers will recognize this as the very same trial that the National Multiple Sclerosis Society has repeatedly refused to fund for reasons that can only be deemed suspect, as I’ve detailed in several previous blog posts (click here and here). The Tisch Center’s trial is currently an early phase 1 study and is in urgent need of additional funding in order to expand into a larger and more comprehensive phase II trial.

As the Tisch Center is not affiliated with any academic institution or hospital and is a completely independent nonprofit organization, its research efforts are entirely reliant on private donations and institutional grants for continuation. Due to funding shortfalls, the trial is currently on precarious financial footing despite showing tremendous potential and promising early results. One would hope that the NMSS would see fit to reconsider its previous withholding of funds and do its part to help further the only FDA approved Multiple Sclerosis stem cell trial in the USA.

As is evidenced by this news segment, the Tisch Center stem cell trial has the potential to dramatically change the MS treatment landscape. I’d urge all who feel that the National Multiple Sclerosis Society should reverse course and support the Tisch Center to contact the Society and voice their opinions. The  email addresses of the Society’s executive staff can be accessed by (clicking here), and the phone number of the NMSS is 1-800-344-4867

Please keep all communications polite, as the NMSS may in this instance be misguided, but it is not an adversary. As my grandmother used to tell me, you can catch more flies with honey than you can with vinegar…

Thursday, October 15, 2015

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

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

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

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

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

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

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

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

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

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

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

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

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

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