Glimmers of Hope for Progressive MS: Human Stem Cell Trial, Biotin Study Both Show Efficacy

Progressive multiple sclerosis is a particularly horrendous and intractable illness. Unlike the relapsing remitting form of the disease, for which there are currently 12 approved treatment options (however imperfect these may be), there is tragically little available for progressive MS patients (one very flawed treatment option for SPMS and none for PPMS). At the recent American Academy of Neurology meetings, held last week in Washington DC, some rays of hope for progressive MS finally shone through, among them studies done on honest-to-goodness human progressive MS patients – as opposed to those done on mice or in test tubes – that show particular promise.

As I’ve written about extensively (click here ), the Tisch MS Research Center of New York is currently conducting the only FDA approved regenerative human stem cell trial on MS patients in the United States. Yes, this is the very same study that the National Multiple Sclerosis Society has repeatedly refused to fund (click here). Though this phase 1 trial is not yet complete, interim results were released at the AAN meeting, and they look impressive.

The Tisch Center utilizes a unique approach to using stem cells to treat MS, quite unlike the techniques used in previous regenerative stem cell trials or the stem cell treatments being offered by for-profit operations scattered around the world. Employing proprietary methodology developed in the Tisch Center’s research laboratories, raw mesenchymal stem cells – harvested from each patient’s bone marrow – are transformed into stem cells specific to the human nervous system, called neural progenitor cells. The 20 patients enrolled in this early stage trial will each receive three spinal (intrathecal) injections of neural progenitor cells, spaced three months apart. The interim results released last week report on the nine patients who have thus far begun treatment (click here).

Of these nine patients, seven displayed some form of disease improvement. Six of these seven patients suffer from SPMS, and one from PPMS. Based on neurologic exams, five of these seven patients displayed improved motor functions, including better balance, increase muscle strength, and improved ambulation. Six of the patients reported better bladder function. No significant adverse events were reported. Here’s a graphic detailing the Tisch Center stem cell trial results on a patient by patient basis, taken from the poster presented at the AAN meetings. To view the full poster, please (click here).

While exciting, it’s important to keep these results in perspective. We’re looking at a very small patient population taking part in an early phase 1 trial whose primary endpoint is establishing the safety of the treatment. That said, given the intractability of progressive MS, seeing any significant improvement is extremely encouraging, and these early results certainly validate the approach to regenerative stem cell therapy being taken by the Tisch Center.

Alarmingly, though, the Tisch Center is now facing a fund-raising crisis that threatens to impede the phase 2 extension of this study, as well as much of the other groundbreaking MS research currently underway in the Tisch laboratories. In previous posts I’ve expressed my extreme distress at the NMSS’s repeated refusals to fund research being done at the Tisch Center, and due to unforeseen circumstances the Center’s funding shortfall is now being felt quite acutely. The animal research laboratory used by Tisch Center scientists is being closed as a result of the sale of the hospital in which it’s located (only a block away from the Tisch MS Center), leaving the Center with no viable alternative other than constructing their own facility, which will require a massive fund-raising effort.

Since I’d rather this post concentrate on the research itself, I urge all readers to click here for more information regarding this fund-raising crunch, and to spread the word far and wide. While the Tisch Center is actively conducting the only current FDA approved MS stem cell trial on human beings, the NMSS funds preclinical stem cell experiments being done in test tubes and on mice that, even if spectacularly successful, won’t reach MS patients for more than a decade. Just saying…

(Full disclosure: I am a patient at the MS clinic directly associated with the Tisch MS Research Center of New York, and my MS as well as other physical ailments have been totally kicking my ass lately. So, yeah, I might take this crap just a wee bit personally.)

Another much-anticipated study presented at last week’s AAN conference provided yet more hope for progressive MS patients, though perhaps not as much as originally anticipated. The French pharmaceutical company MedDay released the results of a stage III clinical trial involving the use of massive doses of Biotin to treat patients with Primary Progressive Multiple Sclerosis (PPMS) and Secondary Progressive Multiple Sclerosis (SPMS).

Biotin (vitamin B7, also known As Vitamin H or Coenzyme R) has been used in much lower doses as an over-the-counter “nutraceutical” supplement to treat brittle hair and nails, some skin conditions, and neuropathy brought on by type II diabetes, among other applications (click here). Biotin is known to be necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids (click here).

A small pilot study researching the use of high doses of Biotin to treat MS was conducted by MedDay starting in 2013. This initial study produced astounding results, with 91.3% of the 23 progressive MS patients involved displaying improvements in their neurologic condition (click here). This small, unblinded, non-placebo-controlled trial created much excitement, leaving patients and researchers awaiting the results of a much larger placebo-controlled phase 3 trial, which was completed in late 2014. The results of this phase 3 trial were presented at the AAN conferences on Friday, April 24, 2015.

In this late stage study, conducted at 19 centers around France, patients were given 300 mg of Biotin per day, which is the equivalent of approximately 10,000 times the maximum daily recommended dosage. The study involved 154 patients, 103 given Biotin and 51 given a placebo. The results of this study (click here), while positive, don’t appear to be nearly as compelling as had been anticipated based on the early pilot study results.

The results of MedDay’s late stage study revealed that after 12 months, 12.3% of the Biotin treated patients displayed a verified improvement in disability scores, as opposed to 0% of the placebo group. Secondarily, 4% of Biotin treated patients displayed disease progression after one year, versus 13% in the placebo group. Very few adverse events, all considered non-serious, were reported. While these numbers pale in comparison with those seen in the initial pilot study, they still represent a breakthrough of sorts in treating advanced progressive MS, which thus far has defied almost all attempts at treatment.

Looked at another way, about 1 in 8 patients treated with Biotin saw their disability scores improve, while 1 in 25 saw their disease progress. Interestingly, only 1 in 8 (I’m using ballpark figures here) untreated patients experienced disease progression. While these aren’t the kind of results many hoped for based on the early Biotin study results (9 in 10 patients experiencing neurologic improvement), they are still better than nothing, which is what mainstream medicine currently offers patients with advanced (non-relapsing) progressive MS.

Given these factors, many patients with progressive MS (myself included) have expressed great interest in giving Biotin a try, especially since the stuff is readily available in over-the-counter form. The highest dose capsules commercially available are 10 mg, meaning that a patient would need to take 30 capsules a day to replicate the doses used in MedDay’s trials, which administered 100 mg of biotin three times a day. There are a few serious problems with this approach, though, above and beyond the huge amount of capsules that would need to be ingested to replicate the doses used in MedDay’s trial.

First, the compound used in the MedDay trial is a highly concentrated and purified pharmaceutical grade form of Biotin called D-Biotin, a stereoisomer of Biotin that is extremely bioavailable (easily absorbed by the body) and contains active enzymes (click here). This type of Biotin is generally not available in over-the-counter capsules. Second, over-the-counter nutraceuticals are completely unregulated, and it’s almost impossible to know the purity of the compounds contained within the capsules or what other ingredients might also be present. One study found that a shocking one third of herbal supplements tested contained not a trace of primary ingredient the listed on the bottle (click here)! Additionally, some Biotin supplements contain calcium, which if taken in greater amounts can cause hypercalcemia, a potentially very serious medical condition (click here).

After consulting with a naturopathic physician, I'm looking into procuring ultra high grade, USP certified (click here) D-Biotin from a reputable wholesaler and having it put into properly dosed capsules through a compounding pharmacy (I'm doing this with my naturopath's help, of course, and will need a prescription in order to get the drug). While this approach is likely to be much more expensive than using over-the-counter product (probably about $300-$400/month), it will offer the best chance at replicating MedDay’s trials, and would certainly eliminate the vast uncertainties involved in consuming huge quantities of over-the-counter nutraceutical supplements.

So, there you have it, two clinical trials targeting progressive MS in very different ways, but coming up with encouraging results to one degree or another. While the Tisch Center stem cell therapy is still in early trials and is at least several years away from moving from the experimental stage to general clinical use, MedDay’s Biotin compound should be ready for FDA approval by the end of this year, and highly motivated patients might try to get a head start on things by taking matters into their own hands. Although the results of MedDay’s late stage phase 3 trial were a bit underwhelming, they do represent an important advance over the status quo, and many progressive MS patients are well past the “any port in a storm” stage.

As mentioned above, though, please take caution if you plan on going the over-the-counter Biotin route. Here’s a video featuring the terrific John Oliver explaining in his usual brilliant and sardonic fashion the pitfalls and perils of placing your trust in the nutritional supplements industry. If you are planning on trying over-the-counter biotin in the quantities required by the MedDay trial, this is an absolute must watch:

A Stranger in Strange Lands

Way back in the summer of 1989, just about a month before my 26^th birthday, I unintentionally found myself living in South Florida. An unfortunate confluence of bad decisions on my part, ill will on the part of others, and an ample dose of plain old rotten luck landed me in an environ in which I never intended to land. Without getting into the gory details, suffice it to say that for me Florida was a refuge of last resort, a place I had visited fairly often (I’d long had family living there) but one which I’d never even considered a spot in which I might one day actually reside. In fact, if asked just a few months before if my living in Florida were even a remote possibility, I would have looked at the questioner as if they were totally insane. I knew on a very basic level that the Sunshine State and I would never make for a comfortable fit, but lo and behold, there I was, an accidental Floridian, ill-suited to the place by any number of measures.

Now, there’s nothing inherently wrong with South Florida; some people find the locale a paradise. I’m just not one of those people. Before arriving in Fort Lauderdale I had spent my young adult years living a quirky Bohemian existence, primarily in Boston but also for a short time in my native New York City. I’d never held a full-time job and had inhabited an eccentric and lively subculture of writers, artists and musicians, or at least wannabe writers, artists and musicians, that formed what sociologists refer to as an urban tribe, with its own customs, values and interests that quite often veered significantly from those of the mainstream.

In both Boston and New York such enclaves were woven into the fabric of city life and like-minded spirits abounded. Fort Lauderdale, though, held little in the way of such a community. Either by nature or nurture (or both) I was temperamentally completely at odds with the place. Whereas I’d always deeply appreciated the muted beauty of a cloudy day, Florida exalts in its status as The Sunshine State. Fort Lauderdale is renowned for its beaches; I detest the feeling of sand between my toes. If Florida is Ying, I am Yang. Despite Zen ideals, this particular combination of Ying and Yang did not produce harmony, but instead a feeling inside me of perpetual discord that eventually led to a crisis of spirit.

Despite my ongoing sense of otherness I remained in Florida for about 10 years, a fact I still have difficulty reconciling, particularly to myself. When I arrived in Florida I was pretty much out of options and had hazy plans of staying maybe 6-12 months. And then I suppose life just took over. I halfheartedly stumbled into my first ever full-time job, working as a low-level video producer for a local cable television company, a quirky enough position in which I had lots of fun but made very little money. In spite of my always feeling like a piglet among puppies I eventually managed to fashion an active social life and find friends and lovers, and though I grew extremely close to some of them, many were quite different from the folks I naturally gravitated to up North. This taught me a lesson that remains one of the few net positives that I took away from my time in Florida: to not prejudge people based on externals alone. Given half a chance, people of all stripes can be full of delightful surprises.

After a few years, my oddball job working for the cable company led to a more lucrative and much more structured position in a marketing company, and that to yet another career builder in an even more stifling corporate environment. While this evolution provided financial comfort, it also shoehorned me into a day-to-day lifestyle that only a few years earlier I had adamantly and vociferously forsworn. At times I barely recognized the clean-cut young man knotting a necktie who looked back at me in the mirror, feeling as if I were living a life deep undercover or, worse yet, as a feckless imposter. Beneath the surface my native eccentric impulses still simmered, but somewhere along the line I had allowed myself to become a passionate man living a passionless existence.

Along the road to this begrudging semi assimilation I lost track of who I once was, the essence of “me” that existed still at the core of my being. This created a spiritual and psychological void that led to terrible cognitive dissonance, manifesting as what I can only describe as a desiccation of the soul. As the years wore on I grew increasingly discontented but found myself caught in a self-imposed catch 22, shackled by the responsibilities of the very lifestyle that was causing me such massive dissatisfaction. The mental blinders I developed in a misguided attempt to stay the course served also to keep me from seeing a way out.

During my last few years in Florida I started experiencing a variety of strange physical symptoms that subsequently turned out to be a subtle presage of the physical crisis to come. Finally, after nearly a decade, the breakup of a long-term romantic relationship provided me with some long overdue escape velocity and I made my way back to New York. Despite the tropical beauty of parts of South Florida, my favorite view of the place turned out to be the one in my rearview mirror.

Arriving back in New York felt like pulling on a favorite pair of well broken-in jeans, once thought lost but happily rediscovered. Before long things started to almost magically fall into place; I reconnected with dear old friends, landed a promising high profile job in a very prestigious but funky outpost of a worldwide mega-media company, and, just a little over a year after returning to NYC, met the marvelous woman who I would eventually marry.

Things seemingly couldn’t have gone much better until – after four years back in New York and just weeks before my first wedding anniversary – the nagging physical symptoms that began back in Florida finally became too pronounced to ignore and I was soon diagnosed with progressive multiple sclerosis. Even though I’d had a sense for years that things weren’t quite right physically, nothing could have prepared me for the maelstrom that would soon erupt within and around me as I was forced into the world of creeping paralysis, once again a stranger in a very strange land, limping down a path for which no roadmap existed. My discarded crisis of spirit was now replaced by a crisis of body.

Despite the best efforts of me and my doctors my disease progressed quite rapidly. Less than four years after my diagnosis I was forced to quit work and go on long-term disability. About a year and a half later I found myself in a wheelchair, the right side of my body withering and my left side beginning to weaken. Quite unexpectedly, these developments allowed parts of me that had been buried for decades to take root and blossom. The gaping holes in my life left by the excision of work and social obligations were soon filled by pursuits and passions that had for far too long been subjugated by the realities and responsibilities of adulthood. Further, my attempts to save my own backside by learning as much as possible about my disease and the ongoing research into treating it injected a sense of purpose and glimmer of light into this murky and frightening new world.

Not to say that my getting sick was in any way fortuitous or – gack! – a blessing. But my increasing disabilities served to strip my life bare as I became less and less able to utilize the trappings of the land of the healthy, rendering an ever-increasing list of everyday objects little or no use to me, luxuries and perceived necessities that had served not too long ago as balms providing superficial comfort and satisfaction, particularly during my wayward days lurching through life in South Florida.

Slowly a curtain of artifice began to lift, and looking at the healthy world from the outside in revealed the synthetic nature of the forces driving most people’s lives; the unappeasable wants and desires conjured by insatiable consumerism, the intentional discontent fostered by a social order that thrives on keeping its populace in a perpetual state of simmering dissatisfaction. During my Florida days these machinations led me down a primrose path, but in my increasingly compromised physical state I began to see with startling clarity that the frenzied world of imposed needs and longings that I once inhabited depends on no thing – no object, person, or sense of self – ever being good enough. No wonder antidepressants are being gobbled by the ton.

Paradoxically, the crisis of body that came all too soon on the heels of my Floridian crisis of spirit allowed that spirit to take root and blossom, freed by unfortunate circumstance to flourish in the absence of any preconceived notions of success and failure. Perhaps the most maddening aspect of this creeping paralysis is that it very likely will never allow me to fully utilize the lessons learned, to put into action in that ever receding land of the healthy the bits of wisdom and insight garnered by being forced to endure what I once believed to be unendurable. Has the experience of prolonged debilitating illness left me unsuited for a life back among the healthy? Now there’s a problem I wouldn’t mind facing, to once again be a stranger in that strange land.

As for the world I now occupy, this truly bizarre land of multiple sclerosis, I intend to always be a stranger within. Although so many of my fellow inhabitants are among the most inspiring people I’ve ever come to know, I will not – I cannot – accept citizenship in this nation. If I was haphazardly thrust out of my element by my never intended move to Florida, I’m a willful alien in this place. No MS green card for me, thank you.

And so I find myself a stranger in two strange lands, the worlds of the sick and the healthy. Maybe it was my destiny to always be the stranger, or perhaps I’m just strange. In either case, vive la diffèrence!

Well, just as long as I don’t have to vive it in Florida…