All I Want for Christmas Is a Cure for This Damned Disease!

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I had a slight meltdown while serving as a semi-official MS patient advocate last week. Please let me explain…

I was invited to take part in a conference call organized by a significant multiple sclerosis consortium. The group is planning an MS conference which will take place over several days, with one of the days devoted to patients and patient education. My purpose on the call, along with several other patient advocates, was to help decide which seminar topics would be most interesting and useful for patient attendees of the planned meetings. In advance of the call I was supplied with a list of potential subjects and was told to be ready to choose which I thought should be included as part of the conference program.

As I perused the list, which included items such as "2018 MS Drug Pipeline" and "Mindfulness and MS", I found myself surprised and then increasingly angered by one glaring omission: there was no mention at all about the search for a potential cure for MS. This annoyed me to no end. After all, shouldn’t one of the primary goals of every MS Association, researcher, and neurologist be figuring out how to put themselves out of business by curing this damned disease? I thought it quite telling (and nauseating) that the planners of this MS conference hadn’t thought enough of this subject to even include it as part of the equation.

Despite assurances to myself that I would remain calm during the conference call, once it came my turn to speak I just couldn’t help myself. What began with my evenly pointing out that the prospect of a cure had somehow been overlooked quickly devolved into a sputtering, barely coherent chastisement of the entire MS medical establishment. Let’s not forget, the field of MS neurology was not so long ago considered a medical backwater, but has since been transformed into one of the biggest cash cows in all of modern medicine, all on the backs of outrageously expensive pharmaceutical products that may curtail disease activity but do absolutely nothing at all to cure MS.

Is this really where the MS status quo now resides? A place where we must accept that disease management is the best we’re going to get? Where patients struck with a hideous illness should be content or even grateful that the modern medical divinities have graced some of them with the ability to keep their potentially crippling malady in check for who knows how long? Where the torrents of cash generated by insanely priced drugs have so corrupted the MS establishment from top to bottom that the prospect of a cure seems unfit for conversation in polite company – why, for fear of spooking the goose that lays perpetual golden eggs? And what about those of us with progressive disease, who now have a whopping total of one approved drug that might, just might, slow the insidious decline of a subset of us by a less than dazzling 20%-25%? I readily admit that the disease modifying drugs currently available do dramatically improve the quality of life for many of the patients taking them– they also carry with them long lists of frightening and sometimes fatal side effects – but they do nothing at all towards stomping out MS. Forgive me for not genuflecting at the feet of the MS gods. How about this? Come up with a drug that cures my creeping paralysis and I’ll genuflect my ass off.

Some of the other patients on the conference call responded to my little tirade by saying that they’d given up hope for a cure in their lifetime. Though I do understand the frustration that lies at the root of this sentiment, to that I respectfully say “bullcrap”! Each of the top-selling MS drugs generates profits measured in billions of dollars per year; you’d think that some of that money might be spent looking for the cause of and then cure for multiple sclerosis. Instead, we have pharmaceutical companies devoting more money to marketing than to research (click here), and the funds that are spent on research are almost exclusively directed towards finding newer and better ways of manipulating the human immune system. NEWSFLASH TO MS RESEARCHERS: the aberrant immune response seen in MS patients is not the cause of the disease, it’s a symptom of some much deeper ill. Though the following analogy may be a bit of a stretch, treating MS by suppressing the immune system is like treating a broken leg with painkillers. It may make the patient feel better, but it doesn’t do a damned thing towards fixing the underlying problem.

At this point, you might rightfully ask, so, Mr. Smarty-Pants, if you’re so clever and smug and full of yourself, where would you suggest we start this quest for an MS cure? Well, I’m glad you asked. Even though I’m not a physician or researcher, I think I have a few good ideas. Here are just some of them:

• We’ve known for years that the Epstein-Barr virus is somehow implicated in the MS disease process. In fact, there seems to be such a close relationship between EBV and MS that some researchers have gone so far as to state that if a person doesn’t have EBV, they don’t have MS (click here). Certainly, EBV alone doesn’t cause MS, but in conjunction with specific genetic predispositions, it may just be the fire starter. We now have the ability to map patients’ genomes, so shouldn’t there be at least a few researchers laser-focused on understanding the interaction between EBV and patient genetic profiles in an attempt to get to the guts of the problem? At the very least, a comprehensive database of the genetics of MS patients should be started posthaste so that gene variants and epigenetic changes can be detected and identified.

• It’s been observed that HIV patients taking powerful antiretroviral drugs seem to develop MS in far lesser numbers than the general population (click here) and that HIV patients who already have MS often see their disease go into nearly complete remission once starting these drugs (click here). Again, why isn’t this a subject for intense scrutiny? Especially since one of the most commonly used anti-HIV drugs, AZT, has been shown to have anti-EBV properties (click here)? Please note, there was one trial of an anti-HIV drug, Raltegravir, on MS patients. This trial failed, but Raltegravir does not effect EBV.

• HSCT, the form of stem cell therapy that first eradicates an MS patient’s immune system with strong chemotherapy drugs and then reboots it via stem cell transplant has been shown to put properly selected multiple sclerosis patients into long-term remission (click here). Shouldn’t these patients be carefully tracked and tested to see just why this treatment can be so incredibly effective? Is it simply that their reconstituted immune systems are no longer autoreactive, or might there be some other reason? Does HSCT not only put MS into remission but actually cure it, with those patients who see a resumption in disease activity somehow developing MS anew after coming into contact with some environmental trigger? The fact is that Epstein-Barr virus, when dormant, resides in immune system B cells which are wiped out during the chemotherapy-induced eradication of patient’s immune systems at the start of the HSCT process. This means HSCT rids the body of EBV. Does this allow the genetic triggers of the disease to then reset, putting a halt to the autoimmune process? A shot in the dark, maybe, but one worth examining…
  
  
• Researchers at Harvard are currently studying the use of a century-old tuberculosis vaccine, called the BCG vaccine, to treat patients with type I diabetes, an autoimmune disease. They are reporting remarkable success, completely reversing the disease in some patients (click here). Apparently, the BCG vaccine works on both the immune system and on the genetic level, and thus could theoretically be of use not only in type I diabetes but across a broad spectrum of so-called autoimmune diseases. In fact, before the introduction of the MS disease-modifying drugs, there was promising research into the use of BCG to treat MS (click here), which seems to have been abandoned once money started rolling in from the first MS drugs. Why devote research monies to a 100-year-old vaccine that costs relative pennies when gazillions of dollars can be generated developing a never-ending stream of boutique drugs that profoundly alter the workings of the human immune system, the long-term ramifications of which are entirely unknown? As Deep Throat told Woodward and Bernstein, follow the money…

Okay, in the parlance of corporate speak, I’ve just spitballed a few ideas on which MS researchers devoted to finding a cure for the disease might focus their considerable brainpower. Of course, many of these ideas don’t have near-term blockbuster profit potential, so in the upside down world of pharmaceutical company driven medical research, they likely won’t get much attention. I’ve said it before, and I’ll say it again – capitalism is a wonderful system for creating wealth, but the marriage of capitalism and medicine is proving to be an unholy one. As long as profits take precedence over patients, as is currently the case, cures for any diseases will be rare beasts indeed.

MS organizations should never lose sight of the fact that their prime directive should be hastening their own demise by contributing to the effort to find a cure for the disease. The current status quo must not stand, and patients should not stand for it. I for one will not shut up about this topic, no matter how nuts it may make me seem to those less inclined to histrionics. If MS patients themselves don’t demand better, we will never get better, both figuratively and literally.

Oh, yeah, Happy Holidays!

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Since it is the season of giving, please allow me to recommend two MS nonprofits that are very worthy of your and your families’ and friends’ donations. I’m not suggesting the National Multiple Sclerosis Society, as, quite frankly, they have a vast contribution generating machine that sucks up lots of the cash that might be better directed at smaller MS organizations. Given the topic of this essay, I’m recommending two groups that are striving to find a cure for multiple sclerosis.

The first is the Tisch Multiple Sclerosis Research Center of New York (click here), which is currently in the process of building the largest stem cell laboratory devoted strictly to stem cells for MS, and will soon be starting the only FDA approved phase 2 stem cell trial on PwMS. In addition, the Tisch Center is involved in a wide range of groundbreaking research, from identifying MS biomarkers to understanding the root cause or causes of the disease, without an understanding of which there can be no cure.

My second pick is the Accelerated Cure Project (click here). The ACP is currently focused on the iConquerMS project, a crowdsourced database of information supplied by MS patients that will give researchers worldwide the opportunity to detect patterns and trends in the MS population that very well could provide the clues needed to come up with a cure for the disease. In addition to donating to the ACP, if you’re not already a participant in the iConquerMS project, I urge you to visit their website (click here) and start participating by answering some quick surveys. This is a patient-driven research effort and gives you a chance to join in the search for a cure.

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Finally, here’s a little Christmas present to my dear readers. The following clips are from the exquisite but little-known 1995 film “Smoke”, one of my faves.. Despite the fact that there are no explosions or car crashes, this one of my favorite scenes in all of filmdom, just one friend telling another a compelling Christmas story. Is the story true or made up, and does it matter? The scene features a masterful performance by the great Harvey Keitel playing opposite William Hurt, and touches on just about everything that makes Christmas and human beings such endlessly fascinating subjects.

Please watch both clips to get the full effect (I recommend viewing full-screen), as I couldn’t find a single clip that encompasses the entire sequence. As an added bonus, the sequence finale features one of my favorite Tom Waits songs, Innocent When You Dream. If you’re interested in watching Smoke in its entirety, it’s available for streaming on Amazon (click here). Enjoy!

MS Research Roundup-HSCT, Ocrevus, MS Blood Test, and More

Longtime Wheelchair Kamikaze readers will remember that I used to post articles comprised of veritable potpourris of MS related info on a fairly regular basis, and that I’d title those posts “Bits and Pieces”. I’ve kind of fallen down on the job in that regard lately, but over the last month or so a bunch of MS research related articles caught my eye, so I figured I compile them here. Came up with the snappy and uber-original title “MS Research Roundup” since any readers new to the blog wouldn’t know what in tarnation I was talking about with the “Bits and Pieces” rigmarole. And what’s the use of a rigmarole if people find it befuddling? A befuddling rigmarole defeats the whole purpose of rigmaroles, and that would put me and my readers in a quandary wrapped in a conundrum. Who the hell needs that?

So, without any further bandying about willy-nilly, here are some items I hope you find of interest:

♦ First up, a bit of self-congratulations. The UK-based website Stairlift Reviews (click here) has named Wheelchair Kamikaze one of the 100 Best Blogs for Disabled People and Carers. Much thanks to them, and I must say they’ve done a really good job compiling the list as there are lots of really, really good blogs on there. Pretty sure Wheelchair Kamikaze got in by way of clerical error.

♦ Ocrevus (ocrelizumab) has its much awaited date with destiny on March 28, as it goes up before the FDA for approval. The new MS drug was originally scheduled for FDA review this past December, but the review was delayed due to manufacturing issues. Ocrevus is up for approval for the treatment of both relapsing MS and progressive MS, and if approved for the latter would be the first drug on the market for this form of the disease. Based on the trial results, I’d say the odds of the FDA giving the drug the go-ahead are excellent, especially for relapsing MS. I’d say Ocrevus has at least a 90% chance of approval for relapsing MS. Probably closer to 95%, as a rejection for this form of the disease would really be a shock given the robust trial results. Things aren’t quite as sure for progressive MS, but I’d still peg the odds of approval here at about 70%. I’d say there is probably a 20% chance that the drug is only approved for progressive patients who have enhancing lesions, and a 10% chance that it is rejected outright, most likely because of the higher cancer rates seen versus placebo in the progressive MS trials. I’ll put up a quick post on these pages after the results of the FDA review are announced on Tuesday.

♦ HSCT, the type of stem cell therapy that first wipes out the immune system using chemotherapy drugs and then reboots it by way of bone marrow transplant, has once again been making waves. The results of two trials were recently released, both showing that the treatment is remarkably effective in completely shutting down the disease for years long periods of time in many patients. In one 24 person trial, comprised exclusively of RRMS patients and sponsored by the National Institutes Of Health, 69% of trial subjects experienced no MS progression, relapses, or central nervous system lesions 5 years after undergoing HSCT (click here). Some of them even regained lost function. Pretty damned impressive.

A second study looked at the long-term results of HSCT using retrospective data gleaned from 25 treatment centers around the world (click here). The study looked at 281 patients treated between 1995 in 2006, and found that just under half of the treated patients showed no sign of progression 5 years after treatment. The patient population looked at in this study was about 70% progressive MS patients (the overwhelming majority of these SPMS), which accounts for its lower rate of efficacy than the smaller NIH sponsored study cited above.

Through some physician friends of mine I was able to get my hands on a copy of the actual paper, which revealed that when the numbers were broken down according to disease subtype, 73% of RRMS patients, 33% of SPMS patients, and less than 20% of PPMS patients were progression free after 5 years. It should be noted that there were very few PPMS patients included in this study (only 24 out of the original 281 trial subjects, and only one PPMS patient was tracked through 5 years). The authors of the study conclude by saying that these results warrant serious further trials of HSCT as first-line or second-line treatment in “patients with highly active relapsing MS… Furthermore, our results raise the question whether HSCT may attenuate the progression of disability in patients with progressive forms of MS, a possibility that is more plausible in patients with MRI evidence of central nervous system inflammatory activity before transplant.” Evidence of “central nervous system inflammatory activity” means enhancing lesions as seen on an MRI, and many other HSCT studies have also concluded that the treatment works best on patients exhibiting these types of lesions.

The results of these 2 studies further strengthen the case for the use of HSCT in MS patients who have enhancing lesions. It is beyond absurd that over 20 years since the testing of HSCT on MS patients started, we still haven’t had an actual placebo-controlled trial on what appears to be a highly effective treatment, perhaps the most effective MS treatment to date. This probably has to do with the fact that the pharmaceutical companies can’t make gazillions of dollars on HSCT, since the drugs used to knock out the immune system are all older drugs that have come off patent. Combine this with the fact that HSCT puts patients into long-term remission for years at a time, during which they have no use for the hyper expensive MS drugs marketed by the pharmaceutical companies, and the reasons why HSCT remains understudied becomes a bit less cloudy. MS patients and those who love them deserve more.

I’m working on getting an interview with a prominent HSCT researcher, so hopefully I’ll be able to bring some “straight from the horse’s mouth” info to Wheelchair Kamikaze sometime soon.

♦ For those interested in the history of multiple sclerosis, here’s really good article entitled “The Story of Multiple Sclerosis And Its Major Milestones” (click here). Lots of fascinating stuff here, including the fact that in the 19^th century MS was often treated with bloodletting, leeches to the temple, an all meat diet, arsenic, or injections of silver or gold. Heck, if someone showed me some halfway convincing proof that any of these treatments were of use in treating my non-inflammatory progressive MS, I’d go for it in a heartbeat. Leeches to the temple? Bring. Them. On. Couldn’t be any less effective than all of the other crap I’ve tried in the 14 years since my diagnosis, and at least for a little while I’d have a couple of new pets.

♦ Looks like a blood test that will diagnose MS is going to be released in May, 2017 (click here). Not sure why this hasn’t been major news, since if this is true it’s a really big deal. Multiple sclerosis is notoriously hard to diagnose, with many patients waiting months if not years to get a definitive diagnosis. Damn, I’ve had this thing for at least 14 years and the doctors still aren’t sure if it’s actually MS. According to this article, the blood test is supposed to be 90% accurate. The test looks at a patient’s RNA and genetic profile to make it disease determination. I’ll have to do more poking around on this…

♦ Finally, here’s a New York Times article from 2016 detailing just how misleading some of the prescription drug TV commercials can be (click here). This article focuses on the drug Opdivo, which is targeted at a form of lung cancer. It’s hard to miss the Opdivo commercials here in The States. I’m sure many if not all of the yanks reading this post know exactly which ads I’m talking about. They are the ones that show hearty looking cancer patients staring joyfully up at claims of the drug’s effectiveness projected on the buildings of a big city. Turns out that Opdivo only works in about one in five Stage IV non-small cell lung cancer patients, and in those patients it extends life for about 11 months. Of course, an extra 11 months for a patient dying with lung cancer are priceless, but the ad makes it sound like the drug makes lung cancer just a few notches more serious than a sore throat.

I’m not going to go off on a rant here, I promise, but WHY THE HELL ARE DRUG COMPANIES ALLOWED TO ADVERTISE PRESCRIPTION MEDICATIONS ON TELEVISION?!?! The United States and New Zealand are the only two countries that allow such lunacy, and even the American Medical Association has stated that this practice must be stopped. Maybe if the drug companies stopped spending more on marketing than they do on research (click here) we’d have some drugs for MS that don’t carry with them death as a possible side effect. One thing I’ll say for those leeches to the temples, they didn’t cost $80,000 per year and didn’t cause PML. Of course, they didn’t do anything for MS, so there’s that. But if the leeches were effective, they’d make for some great TV commercials:

Setting: An extreme roller coaster in a giant amusement park. We open with a wide shot of the park, bustling with men so handsome, women so beautiful, and children so adorable that they put to shame the Nazi ideal of human perfection. Amidst the laughter and merriment we find our two thirty-something female protagonists, a stunning redhead and a willowy blonde, energetically climbing into a car on the roller coaster and getting ready for the ride. Both glow with radiant health. The blonde has leeches stuck to her perfect temples, with drops of blood trickling down her almost impossibly high cheekbones.

MS Patient’ s Friend (laughing): “Jane, you’ve got some horrible bloodsucking monsters stuck to your temples!”

MS Patient (cutely giggling): “Oh Susan, don’t be silly. They’re not bloodsucking monsters! They’re Leechabri, my new MS treatment. Last week I couldn’t swallow or get out of bed, but tomorrow I’m climbing Mount Everest!”

The roller coaster then takes off, and the shot widens to follow our heroes as the coaster does a loop the loop. Quick cut to a close-up of our MS patient, laughing hysterically as her leeches flap in the breeze.

And with that image stuck in your mind, I’ll take my leave. I’ll be back with a quick post just as soon as the FDA decision on Ocrevus is announced…

Recent Research on HSCT, the Stem Cell Therapy That May Soon Change the MS Treatment Landscape.

(Please note: the following article is quite long. Though it covers a very important topic and I’ve tried to make it as accessible as possible, I’d suggest getting comfy and grabbing a nice beverage before diving in…)

Over the last six months or so, there has been a wave of new and encouraging research published regarding HSCT (Hematopoietic Stem Cell Therapy) for the treatment of multiple sclerosis. HSCT is the type of stem cell therapy in which a patient’s existing immune system is completely eradicated through the use of powerful chemotherapy drugs and is then rebooted via an infusion of their own stem cells. Some of the results reported have been nothing short of astounding, and even previously skeptical neurologists are now being forced to consider HSCT as a potential game changer that may significantly impact the MS treatment landscape sometime in the not-too-distant future.

So that this article doesn’t take on the length of a Russian novel, rather than getting into the detailed specifics of what HSCT is and isn't I’d like to concentrate on the recent HSCT published research and its implications. For a comprehensive overview of HSCT, please read my previous post on the subject by (clicking here). For a rundown on the different types of stem cell therapies currently being trialed in MS, please (click here).

Just a few things before delving into the research. It’s vitally important that patients not confuse HSCT with regenerative stem cell therapy, which attempts to directly repair the central nervous system damage done by MS. HSCT is a completely different approach with a completely different goal. Regenerative stem cell therapy, such as that being trialed at the Tisch Center in New York (click here) generally does not involve any direct manipulation of patients’ immune systems. HSCT, on the other hand, is entirely directed at providing patients with a new immune system after completely wiping out their presumably defective existing set of immune cells. The two treatment approaches couldn’t be any more different; their only similarity is that they both use stem cells in an attempt to combat multiple sclerosis, albeit in very different ways.

There are currently two forms of HSCT being trialed on MS patients, termed the myeloblative and non-myeloblative treatment protocols. The myeloblative protocol uses a combination of very strong chemotherapy drugs to completely ablate (a fancy word for “destroy”) patients’ immune systems as well as their bone marrow (immune system cells are manufactured in the bone marrow). Non-myeloblative HSCT uses a gentler chemotherapy regimen that takes down the immune system but leaves bone marrow intact. There is some debate among researchers as to which treatment protocol is best suited for combating MS, an issue that is still being sorted out.

There’s also the question of which patients are most likely to respond to HSCT. Because HSCT is directed entirely at replacing a patient’s presumably defective immune system with a new one that doesn’t attack the body’s own nervous system cells, the prevailing thinking is that only patients displaying the hallmarks of immune system driven multiple sclerosis would likely respond well to the treatment. With this in mind, most HSCT research and treatment centers restrict the treatment to patients with active inflammatory MS, meaning that eligible patients must have recently experienced multiple MS relapses and/or displayed enhancing lesions on their MRI images (enhancing lesions are indicators of immune activity within the central nervous system). Since this excludes many secondary progressive (SPMS) and most primary progressive (PPMS) patients, who experience increasing disability in the complete absence of relapses or enhancing lesions, these requirements are understandably the source of much consternation among this patient population (myself included), who are currently presented with no effective treatment options. More on this later.

With these issues in mind, let’s take a look at some of the recently published HSCT research and explore the issues they raise…

A study out of Chicago that used the gentler, non-myeloblative form of HSCT on 151 MS patients (123 RRMS, 28 SPMS) resulted in some startling results on the RRMS patients taking part in the trial (click here). Not only did the vast majority of these patients see their disease stop in its tracks, but a large proportion also saw their levels of disability improve. Four years after treatment, 80% of trial subjects remained relapse free, and 87% showed no signs of disease progression. Furthermore, and perhaps even more astounding, there was a decrease in the disability scores in 50% of patients two years after treatment, and in 64% of patients four years after undergoing the treatment protocol without any further follow-up treatment (click here). Given that a reduction in disability scores is almost unheard of when treating MS patients, these are eye-popping results, to say the least, tempered only by the fact that the SPMS patients included in the trial were reported to have shown no benefit.

This trial was headed up by Dr. Richard Burt of Northwestern University, a leading HSCT researcher. I tried to reach out to Dr. Burt via email with several questions before writing this piece, but unfortunately received no reply. A very informative interview with Dr. Burt is available by (clicking here). If anybody out there knows Dr. Burt, please tell him I’m still patiently waiting for his email reply, fully understanding that he’s a very busy man. In the meantime, if Dr. Burt should find himself in New York City and happens to get run over by a speeding wheelchair, I’ll swear on a stack of research papers that I had nothing to do with it.

A smaller, 25 patient study, called HALT-MS, which used a harsher myeloblative chemotherapy regimen on patients with highly active relapsing disease who had failed to see benefit from at least two previous MS drugs reported impressive interim results (click here). Though study subjects are scheduled to be tracked for five years, the results reported were a snapshot of these patients at the three year mark after treatment. After three years, 78.4% of trial subjects were reported to be free of any disability progression, relapses, or new lesions. Digging deeper into the results revealed that 90.9% of subjects were progression free and 86.3% were relapse free after 36 months. Very impressive.

I managed to get hold of the full published paper of this study, which indicated that although the numbers had not yet been fully crunched, it did appear that the effect of the treatment lessened with time, as fewer patients were reported to be free of signs of the disease at the four and five year marks (68.6% and 58.8% respectively). Again, though, these four and five year numbers were very preliminary, as not all patients had reached this duration after treatment.

A friend of mine, Dave Bexfield, who runs the terrific MS website/forum Active MSers (click here) was one of the participants in the HALT-MS trial. Five years ago Dave was getting absolutely slammed by his disease despite having been on a series of MS drugs. He qualified for the HALT-MS trial and received myeloblative HSCT. His tremendously aggressive RRMS was put entirely into remission for several years, but unfortunately, after five years, Dave recently reported that his disease has shown signs of reawakening (click here) and he is now planning on going on one of the newer, more powerful MS drugs. Dave told me that even though his disease has returned, he has no regrets about undergoing HSCT back in 2010. Without the treatment he is sure the disease would have by now left him completely disabled, and HSCT bought him time at a point when it looked like multiple sclerosis would get the better of him. There are highly effective treatment options available today that weren’t available five years ago, and despite the reemergence of some of his MS symptoms, Dave is very grateful to have taken part in the study.

An Italian team did a head-to-head test of the effectiveness of HSCT versus mitoxantrone (also known as Novantrone) on SPMS patients who had enhancing lesions on their MRIs (click here), the presence of which indicated that they still had an active inflammatory component to their disease.

Currently, mitoxantrone is the only approved drug for use on patients suffering from SPMS. It’s a fairly wicked drug, so toxic to the heart that patients can only stay on it for a limited amount of time. Additionally, mitoxantrone has been linked to a dangerous increase in specific forms of leukemia and lymphoma. As a result of this daunting side effect profile, the use of mitoxantrone has largely fallen out of favor with most MS neurologists.

This phase 2 study used an intensive myeloblative form of HSCT on a small group of study subjects (21, 17 of whom completed the study), and the primary endpoint of the study was a reduction in the number of enhancing lesions detected by MRI. Four years after treatment, HSCT resulted in a 79% reduction in new lesions as compared to those treated with mitoxantrone Unfortunately, no difference in disease progression was reported, but the study was not ideally set up to detect changes in disease progression, a metric which has proven to be very difficult to track even in studies specifically designed to detect disability progression. An editorial accompanying the study, which adds commentary to the statistics provided in the study abstract, should be of interest to all readers (click here).

A very small study out of Hamburg, Germany attempted to directly address the difference in effectiveness of HSCT between RRMS patients with enhancing lesions and progressive MS patients not displaying lesion enhancement (click here). This very small 10 patient trial (four progressive MSers, six with RRMS) compared the results between the two groups two and half years after treatment. The researchers found that although five of the six RRMS patients did show benefit from treatment, none of the progressive patients followed suit. It should be noted that the RRMS patients were considerably less disabled at the start of the study than the progressive test subjects (EDSS 4.25 versus EDSS 6.25).

Previous studies have found that approximately 40% of patients with early PPMS display enhancing lesions on their MRIs (click here) and the presence of such lesions early in the disease may be an indicator of a more aggressive disease course. Patients undergoing the transition from RRMS to SPMS frequently continue to have enhancing lesions for some time after their disease has gone mostly progressive. Remember, enhancing lesions are a sign of active inflammation in the central nervous system, an indicator that the immune system is playing a primary role in driving the disease forward. Since HSCT directly attacks the peripheral immune system, it stands to reason that the treatment would be most effective on patients with active immune system involvement. In the later stages of SPMS, and in the majority of cases of PPMS, it appears that some other as yet undiscovered neurodegenerative process is at work, a process which seems impervious to treatments targeting the peripheral immune system. Studies testing some of the latest potent immunosuppressive drugs – which are highly effective in treating RRMS – on progressive patients have repeatedly failed, the latest such study involving the drug Gilenya (click here). For those of us with progressive MS such failures are very discouraging, and it is with great hope that I’ve looked for hard data supporting the notion that HSCT may benefit even hard-core progressive MSers, which leads us to the final study to be discussed…

Lastly, a study out of Moscow, Russia (click here) provided data suggesting that HSCT might be beneficial to progressive patients who don’t have enhancing lesions (as stated earlier, this includes many SPMS patients and the majority of PPMS patients). Unlike most HSCT treatment centers, the center in Moscow accepts patients with all types of MS (RRMS, SPMS, PRMS, and PPMS), regardless of whether or not they have enhancing lesions on their MRIs or have recently experienced relapses.. A total of 99 patients were included in the study, 43 with RRMS and 56 with various forms of progressive MS.

The summary of this study revealed that 49 months after undergoing treatment, 83.3% of RRMS patients and 75.5% of progressive patients exhibited no signs of relapses or disease progression. After eight years, 45% of treated patients exhibited an improvement in mobility scores, while 45% remained stable. These are compelling numbers, to say the least, particularly for someone like me who has never had enhancing lesions but has nevertheless experienced a constant progression of disability. So compelling, in fact, that I asked a physician friend of mine to provide me the full paper (I could have bought it myself for $40 but most doctors can get research papers for free, and, hey, that’s what friends are for) so that I could dig deeper into this apparently promising research.

Upon reading the full paper (sorry, I can’t link to it because of copyright laws) my enthusiasm was tempered a bit. Although the paper states that only 40% of study subjects had exhibited enhancing lesions before undergoing HSCT, it turns out that this statistic was based on a single MRI done soon before the patients underwent therapy. A single MRI can easily miss enhancing lesions, especially if patients had been on disease modifying drugs, which is why most HSCT centers require patients to have exhibited enhancing lesions and/or relapses (which are almost universally accompanied by enhancing lesions) at some point during the full year prior to treatment.

Additionally, the scope of the disease histories of the patients treated in Moscow varied widely and in many cases was severely deficient. The full paper clearly states this, saying that “patients enrolled in the study previously have been treated in different centers, and the information about disease activity prior in the disease course and its treatment was inhomogeneous and in some cases quite scarce.” I found this sentence to be disquieting, as without comprehensive disease and treatment histories it’s almost impossible to accurately assess the disease state of any individual patient suffering from an illness as complicated as multiple sclerosis. In fact, the abstract of the study, which is available to the general public, even warns that because of this dearth of patient info “comparison with the results in the literature should be done with caution.” This line throws up a big red flag, as the ability to compare and replicate results from study to study is among the foundational basics of the scientific method.

Furthermore, despite publishing statistics that appear to indicate the treatment as practiced in Moscow was effective across a wide spectrum of MS patients, the authors state that “the best candidates for transplantation seem to be relatively young patients with active inflammatory lesions of relatively short duration and rapidly progressive disease, but still low disability scores, unresponsive to conventional therapy.” This was among a number of apparently contradictory elements contained in this research that left me with more questions than answers. While these results certainly can’t be discounted entirely, without a comprehensive, detailed data set it’s impossible to properly discern their value and validity when compared to other studies, a point the authors themselves reiterate on several occasions.

Based on this accumulated HSCT research, certain trends seem clear. HSCT treatment definitely seems remarkably effective on patients with active inflammatory relapsing remitting multiple sclerosis, in the majority of cases resulting in complete remission of the disease for five or more years, sometimes accompanied by a reduction in disability as well. This is far more effective than any of the currently approved disease modifying drugs with the possible exception of Lemtrada, whose mechanism of action in many ways mirrors that of HSCT (for more information on Lemtrada, which was recently approved by the FDA and is covered by most insurance companies, please click here and here).

The safety profile of HSCT as now practiced seems quite robust. None of the above studies reported any HSCT related mortalities, although some serious adverse events above and beyond those that would be considered normal for patients undergoing chemotherapy were described (most in the form of opportunistic infections). Clearly, the decision to undergo HSCT should not be taken lightly, as at its heart the treatment involves using strong chemotherapy drugs to completely eradicate a patient’s existing immune system. Multiple sclerosis is serious business, though, and many patients would gladly accept this risk/reward scenario for a chance at complete remission lasting years or even decades.

Despite the fact that there are credible anecdotal reports on various HSCT websites from progressive MS patients who state that they’ve been helped by the treatment, and even though I’ve desperately wanted – for my own selfish reasons – to find research to back up such statements, I’ve yet to come across any hard data to back up these claims. Research has shown that the treatment can be effective on progressive patients showing signs of active inflammatory disease (enhancing lesions), but there is little hard objective evidence to support the notion that HSCT benefits patients experiencing progression in the absence of active inflammation.

Because the rate of disability progression varies widely from patient to patient suffering from progressive MS, and can sometimes temporarily “plateau” or even cease entirely, predicting disease progression can be quite difficult, even for patients themselves. Using myself as an example, my wife likes to chide me that I’ve been telling her that I’ll probably be bedridden in six months for the last five years. In order to properly assess the effectiveness of any treatment for progressive MS using disability scores as markers, studies would need to last much longer than the 2-3 years typical MS trials generally run, which is among the reasons why so few trials on progressive MS have been conducted. Even in the recent, much talked about successful study involving the use of biotin to treat progressive MS patients (click here), it was shown that after one year only 13% of patients taking placebo showed evidence of disease progression (compared to 4% taking biotin). I certainly hope that the patients with nonenhancing progressive MS reporting benefit do turn out to be success stories and that some form of HSCT does demonstrably prove effective on noninflammatory multiple sclerosis, but so far, at least, the data is lacking.

Also lacking is long-term data on the durability of HSCT derived benefits on patients of all stripes. One older study (click here) looked at patients with aggressive multiple sclerosis 15 years after treatment and found that 44% of patients who had exhibited enhancing lesions before treatment and 10% who didn’t remained progression free. It should be noted that the patients included in this study were treated with earlier, much harsher forms of chemotherapy, and one would hope that the refinements made in the technique more recently would increase durability.

Although all of the studies reported on in this article are considered early to mid-stage trials, they do suggest that HSCT is an extremely promising and potentially game changing treatment for multiple sclerosis. Further trials will be necessary before HSCT receives any kind of official approval for the treatment of multiple sclerosis. Although the treatment is being offered to patients in quite a few clinics around the world, the cost is quite high and most insurance companies will not cover the expense. Given the exorbitant cost of multiple sclerosis drugs, though, as more reliable data is released this situation should change. Paying $100,000 for a one-time treatment that keeps the disease at bay for even 5-7 years is far more cost-effective than paying the roughly $50,000-$60,000 per year currently charged for the FDA approved disease modifying drugs, a point that I’m sure will not be lost on the insurance company bean counters. It should be interesting to see how the pharmaceutical companies react to the HSCT threat to their bottom lines.

Those patients currently considering HSCT therapy should limit their choice of treatment centers to those which have extensive experience administering HSCT, as study after study has shown that safety and efficacy increases exponentially with the number of procedures done. This treatment is not to be taken lightly, and cutting corners for cost or convenience could prove quite the egregious mistake.

Given the current quickening pace of HSCT research, I would guess that the treatment could approach widespread acceptance sometime within the next five years, as long as the financial considerations of the pharmaceutical companies don’t get in the way (and that may prove to be a mighty big if). Based on the latest data, once approved HSCT should prove to be the most effective treatment available for patients with very aggressive active inflammatory multiple sclerosis, but will likely be reserved for those patients who have first failed current frontline therapies. As for patients with nonenhancing progressive disease, though objective hard data supporting the use of HSCT is lacking, given the anecdotal evidence I hope and expect expect future research will be done on such patients in an attempt to clarify the matter. The stakes are quite high for these patients, and even if the odds of success seem slight, the potential gains warrant further investigation. With neuroregenerative and neuroprotective compounds now in the research pipeline, and with HSCT offering so much promise, there is much reason for MSers to harbor hope for a brighter future.

Stay strong, my friends…

Geez, what was that I said about this article not becoming as long as a Russian novel? Maybe I should change my name to Tolstoy (many apologies to Tolstoy)…

Man Bites Dog (or, MS Patient Beats Insurance Company after Stem Cell Transplant, to the Tune of $400,000)

(c) GoGraph / lhfgraphics

Oh, the many pleasures of Multiple Sclerosis. In addition to the physical and psychological toll taken by the disease, MSers also have to deal with a medical establishment that at times seems purposely set up to make being sick as hard as possible. Here in the USA, one of the most infuriating components of that medical establishment is quite often the private health insurance companies, upon whose whims many patients rely on to pay for such superfluous luxuries as vital medications, essential treatments, and indispensable mobility devices.

In my 11-year career as a patient with a progressive disabling disease I’ve been subject to an almost countless number of frightening medical procedures, the prospect of any one of which would have made the healthy me ruin my pants. Despite the horrid nature of some of these procedures – from needles in the spine to having tubes the size of fire hoses stuck into my veins to tests involving electric shocks of varying intensities – I’d have to say that the source of some of my most prolonged periods of agony have been long and drawn out battles with insurance company telephone tormentors who seem trained by the spirit of Marquis de Sade himself to extract as much psychic pain as possible while doing their god-awful best to avoid providing even the merest dribble of satisfaction.

Given my numerous nerve-racking experiences dealing with the insurademons, it was with great relish that I read the heroic man versus insurance company saga of Mr. Dave Bexfield, which was recounted in the August 3, 2014 edition of the New York Times (click here). I’ve been acquainted with Dave, at least in the virtual sense, for several years through our interactions on various Internet sites, forums, and email. We finally actually spoke to each other last week, as I was preparing this piece. Dave is the creator of the website ActiveMSers (click here), a vital resource for MS patients looking for inspiration and info on how to stay as physically active as possible. The site includes Dave’s blog, interactive forums, tips and tricks, and reviews of all kinds of gear designed to help people with MS stay in the game, so to speak.

Back in 2010 Dave underwent HSCT (hematopoietic stem cell transplant), a stem cell procedure that, in a nutshell, gives MS patients (or patients with a variety of other so-called autoimmune disorders) a new immune system by first destroying their old one through the use of powerful chemotherapy agents, and then resetting it via a stem cell transplant. For more info on the procedure, please refer to my last Wheelchair Kamikaze post, in which I wrote extensively about HSCT (click here). The treatment successfully put the brakes on Dave’s very aggressive relapsing remitting multiple sclerosis, but also left him $200,000 in the hole, a situation which precipitated an epic four-year Battle Royale with his insurance company.

In order to fully understand the majesty of Dave’s victory over his insurance company, I think a little background is in order. Back in 2005, Dave experienced his first MS symptoms, in the form of vision problems and strange sensory experiences. A few months later he suffered his first full-blown relapse, which resulted in the entire right side of his body going numb. After going through the usual diagnostic workup (MRIs, spinal fluid analysis, etc.) he received a verdict of MS. Over the next four years, despite being on the disease modifying therapies Copaxone, Rebif, and finally Tysabri, Dave’s disease slowly progressed, with intermittent relapses, until very suddenly a number of severe relapses put his MS progression into hyperdrive, leaving him at times barely able to take a step.

Just as he was reaching the point of desperation, Dave learned of an National Institutes of Health (NIH) sponsored HSCT study being conducted at the MD Anderson Cancer Center in Houston, Texas. He was accepted into the study, and was deemed the ideal candidate because of the very aggressive nature of his RRMS and his corresponding diagnostic test results. Unfortunately, after receiving this good news came some bad. Due to cuts in the federal budget, the National Institutes of Health, though still involved in the study, could no longer pay for the treatment. If Dave was to participate he would have to cover the entire $200,000 price tag himself. Yikes, to say the least. Dave lobbied his insurance company for financial assistance, but his pleas were rejected outright because of the experimental nature of HSCT treatment. Ultimately, Dave managed to cobble together the $200,000 by draining his savings and through the generosity of his immediate family.

Dave underwent HSCT in 2010, and though the treatment itself was no picnic, it did successfully slam the brakes on his multiple sclerosis, which had turned so aggressive that Dave believes the treatment saved his life. He’s had absolutely no relapses or further progression of his disease in the four years since undergoing HSCT. Of course, there’s no guarantee that his disease won’t mount a counteroffensive at some point in the future, a possibility which he acknowledges, but what MS patient wouldn’t gleefully accept at least a four year truce with their disease, during which the progression of their illness was stopped cold, free from drugs or any other form of treatment? You can read more about Dave’s HSCT experiences on his website (click here).

One might think that this would be the happy end of the story, albeit one with quite the hefty price tag. Just a few months after his stem cell treatment, though, Dave’s insurance company suddenly decided that it would indeed start paying for some forms of stem cell therapy for multiple sclerosis patients, though no such therapy had received any kind of official approval for this use. Dave contacted the company in an attempt to get reimbursed for his treatment expenditures, but was told that he was too late, and that the timing of his claim was simply “unfortunate”. Thus began a gargantuan four-year battle between Dave and his insurer, one which found Dave, with dogged (some might say maniacal) persistence, going to extreme measures to try to prove his case. Through the magic of Google he managed to uncover confidential files that directly contradicted much of what his insurance company was telling him – that they were merely following government mandated guidelines, and thus really had no choice in the matter – and Dave even went so far as to file a Freedom Of Information Act request to uncover yet more evidence of malfeasance on the part of his insurance company. You can read a more extensive, blow-by-blow account of the cage match between Dave and his insurance company on his website (click here).

During his four year struggle with the Insurazombies, Dave contacted a consumer advocate reporter at The New York Times, David Segel, who calls himself “The Haggler”. The Haggler lobbied the insurance company on Dave’s behalf, at first with no luck. Some months later, Dave then provided the Times reporter with some newly uncovered and extraordinarily damning evidence against the insurer, and The Haggler once again contacted the insurance company’s top executives, this time with proof that the company had lied not only to Dave but to the New York Times as well. As if by magic, a few days afterwards Dave found himself having lunch with both the President and the CEO of the $2 billion a year insurance company, during which they informed him that they had, by the good graces of the universe, suddenly experienced a change of heart; not only would they pay Dave the approximately $200,000 cost of the HSCT procedure (which, incidentally, is less than they would have spent on him by now for FDA approved MS medications if he were still taking them, which he certainly would have had he not undergone HSCT), but also the interest that the money would have accrued over the past four years, which came to just about another $200,000! Yes, the end result of Dave’s single-minded crusade to get his due was a check in the whopping amount of slightly over $400,000. Score one (or 400,000) for the good guy…

This David Bexfield versus Goliath story is an extreme example of the trials and tribulations many patients with chronic diseases face when trying to deal with their insurance companies. The problem boils down to a basic conflict of interest: though the insured are the insurance companies’ customers, they are also the determining factor in how much revenue these companies ultimately generate, even if they operate as nonprofit organizations. The less money an insurance company has to pay out to its customers, the better its bottom line. In a world where the profit motive trumps all else, this dynamic can set up some dicey situations for sick people trying to get the best health care possible, and even for those just trying to get the basic necessities required to live with their disease.

My own experience with health insurers has been almost schizophrenic. At times these companies have been incredibly cooperative, yet on many other occasions they seemingly took their tactics directly from the handbook of the Spanish Inquisition, making the prospect of dealing with their telephone representatives as appealing as an invitation to a potluck dinner at Hannibal Lector’s place. I can identify no rhyme or reason behind these vacillations in the behavior of insurance companies. In fact, many times they seem counterintuitive.

For example, this past fall, my insurer unhesitatingly approved my being treated with a rarely used and extraordinarily expensive drug, to the tune of $150,000 (the treatment turned out to be an absolute disaster, which you can read about by clicking here). Yet, only a few months before, this very same company had me alternately begging, screaming, whining, wailing, bellowing, whimpering, and very nearly bursting several very important blood vessels while trying to get approval for a new wheelchair, without which I would have had to change the name of this blog to Bed Kamikaze. The twisted and convoluted course of my six-month struggle to get a piece of gear that was an absolute necessity at times had me questioning my own sanity as well as the very notion of a just universe, and whether or not I might somehow have been drafted into the dyspeptic nightmares of a sadistic surrealist who had eaten one too many enchiladas right before bedtime.

My wheelchair saga played out over an innumerable number of phone calls, and it often seemed as if the Insurafiends were inventing new tactics and excuses even as I was talking to them. My wheelchair provider was “out of network”. Yes, but I had out of network coverage and was willing to pay the portion not covered by my insurer. Paperwork faxed to the insurance company mysteriously disappeared in the Bermuda triangle that apparently existed between my wheelchair vendor’s fax machine and theirs, and when by some miracle it was finally received on their end (with confirmation), it was inevitably lost “in the system” or found to be lacking some key bit of information or arcane equipment code, thus requiring the process to begin all over again.

Once the paperwork was in order, the Insuraschmucks suddenly decided that the specifications of the chair I had chosen were outside of acceptable parameters, and so couldn’t be covered. Mind you, it was the exact same model of chair I’d been using for the past five and half years, only with some added functionality made necessary by the increased level of disability I had accrued through the intervening years. I was told I could appeal the decision to some higher level of Insurabastards, which of course I did. After violating their own self-imposed deadlines for decision-making several times, the senior Insurapricks deemed that, yes indeed, my chosen chariot would be covered thanks to my physical decrepitude, as vouched for by my neurologist. And then came the folly of all follies; the Insurascum insisted that they couldn’t reveal how much money they’d reimburse until the chair was actually ordered, but how could I place an order for the chair until I knew whether I’d be on the hook for $1000 or $20,000? Arghhh…

In the years since my diagnosis, I’ve learned that all of the convoluted tactics employed by the health insurance companies to keep from paying legitimate claims can be boiled down to three words: delay, delay, delay. Their goal is quite simply to wage a war of attrition, frustrating the claimant with technobabble, feigned incompetence, and arbitrary rules and regulations until the sick person gives up due to frustration, physical and mental exhaustion, or the mistaken belief that they are somehow in the wrong. The insurance companies have nothing to lose by playing these games; the longer they hold onto your money the more interest they earn on it, and in fact many if not most claimants do eventually wave the white flag after months or years of interminable mindbending insurabullshit.

All of this corporate hornswaggle would be bad enough if it were employed only on the hale and hearty. However, the hale and hearty aren’t typically the ones filing claims with their health insurance companies. During the trench warfare in which I was forced to engage in order to get a new wheelchair, in times of desperation I would remind the Insurabeasts on the other end of the line that they were talking to somebody who was just about three quarters completely crippled. And that this cripple was only trying to get himself a new wheelchair, which due to my progressing crippledness had become an vital requirement. It wasn’t as if I was trying to get them to pay for a spa vacation in Shangri-La. No matter, rules are rules, even when they are invented, bent, and broken by the very people spouting them.

So, three cheers for Dave Bexfield, the man who managed to topple Goliath while also landing a solid right hook on the chin of his disease. Give thought, though, to those poor souls who through no fault of their own don’t have any health insurance, and are left to somehow fend for themselves in the world of the Multiple Sclerosis Industry and its hyper inflated prices. I’m sure those in countries outside of the US, who don’t have to deal with private insurers, have their own horror stories and headaches, both literally and figuratively. There just seems to be something sadly broken in a world where sick people have to actively fight not only to try to get better, but often just to maintain their sickly status quo. Good grief…

HSCT – Will This Form of Stem Cell Therapy Soon Become the Standard ofCare for Many MS Patients?

English: Cervical spine MRI with enhancement showing multiple sclerosis (Photo credit: Wikipedia)

Hematopoietic Stem Cell Therapy, now there’s a mouthful. More commonly known by its initials, HSCT, this form of stem cell treatment, first tried on MS patients back in the mid-1990s, is beginning to demand widespread attention from doctors and patients alike. Why? Well, one recent study found that when applied to properly selected patients, nearly 80% showed no sign of multiple sclerosis disease activity five years after treatment (click here). No relapses, no new MS lesions, no disease progression – none. Eye-popping results to say the least, all the more so given the fact that these patients were treated on a one time only basis with no follow-up drugs or therapy required. Results like these have led even some mainstream MS neurologists to begin looking at HSCT as perhaps evolving into the standard of care for many patients in the not-too-distant future.

With growing momentum, stem cell therapies of all types are creating a huge buzz in the MS community. While one form of stem cell therapy – that intended to regenerate damaged nervous system tissue – is clearly still in its experimental infancy, another, hematopoietic stem cell therapy, which seeks to reboot the immune system, has been used on MS patients for almost 20 years. Early attempts at using HSCT to treat MS, though at times producing encouraging results, were fraught with danger, with as many as 10% of test subjects dying as a direct result of the procedure. Recent refinements in technique, better patient selection, and a growing knowledge base are now bringing HSCT closer to mainstream use as efficacy rates have soared and mortality rates have dropped dramatically. In the case of the best treatment centers, mortality rates have dropped below 1%, with no deaths reported over the last five or so years.

It’s very important to understand that there are currently two wholly separate and completely different approaches being explored for using stem cells to treat multiple sclerosis. Both hold tremendous promise but go about their business in entirely different ways, and care must be taken to never confuse the two. Regenerative stem cell therapies, almost all using some form of mesenchymal stem cells, seek to repair brain and spine tissues damaged by MS, while HSCT is focused entirely on the immune system and does not directly address damaged nervous system tissues at all. This post will deal exclusively with HSCT. For more info on the differences between these two stem cell methodologies, and more details on the experimental regenerative therapies, please refer to a previous overview of stem cell therapies for MS that appeared on Wheelchair Kamikaze last fall (click here).

So, first things first – what exactly is HSCT? In practice, HSCT is very similar to the bone marrow transplants that have been used to treat patients with leukemia and other cancers of the blood for decades. As a therapy for multiple sclerosis, the process begins by collecting a patient’s own stem cells, either through bone marrow harvesting or blood draws. Once collected, these stem cells are stored, and sometimes multiplied, in sterile laboratory conditions.

Then comes the dramatic part – the patient’s immune system is ablated (a polite way of saying destroyed) over the course of several days using powerful chemotherapy agents. Depending on the clinic treating the patient, a variety of drugs or combination of drugs is used, some more intense than others. The goal of this “conditioning regimen” is to leave the subject with no functioning immune system, obviously a very vulnerable state during which the patient must be kept in isolation to prevent exposure to any possible contaminants or infectious agents. While undergoing this conditioning regimen, patients typically suffer many of the common side effects of chemotherapy, including hair loss and nausea.

Once the immune system has been eradicated, the previously harvested stem cells are intravenously infused back into the patient’s body, where over the course of several weeks they rebuild the immune system, effectively giving the patient an entirely new array of immune cells. In theory, this brand-new immune system shouldn’t have the destructive tendencies that led their old immune cells to attack the patient’s own central nervous system tissues, the mechanism that is believed to cause the damage and lesions that give multiple sclerosis its name.

Though this may seem like a sledgehammer approach to treating MS, recent studies have shown HSCT to be astoundingly effective when used on properly selected patients. One recently published study followed 52 Swedish MS patients that were treated with HSCT (click here). At five years, relapse free survival was 87%, MRI event free survival 85%, EDSS score progression free survival 77%, and disease-free survival (no relapses, no new MRI lesions, and no EDSS progression) was 68%. The presence of Gadolinium enhancing lesions prior to HSCT was associated with a significantly higher degree of favorable outcome (79% exhibiting disease-free survival at five years). The study’s authors conclude that that “HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centers.” Other recent studies looking at the efficacy of HSCT have found similar results (click here and here). Outcomes such as these give ample reason to sit up and take notice, despite the admittedly frightening prospect of the use of intense chemotherapy conditioning regimens.

One must keep in mind that despite recent advances in treating MS with a new generation of immunosuppressant drugs, the disease in its most serious forms remains a brutal beast intent on laying waste to many of those it afflicts. Next generation MS drugs such as Tysabri, Gilenya, and Tecfidera are proving to be potent in managing the disease in those patients on whom they are effective, but these drugs must be taken indefinitely and each has their own set of possible serious side effects that give many patients pause. HSCT, on the other hand, is meant to be a one-time treatment, after which properly selected and treated patients are proving to show a remarkable degree of sustained disease-free existence, with some even experiencing a reversal in disability status (click here). While no responsible person is calling HSCT a cure for MS, and undergoing the treatment is no walk in the park (intense chemotherapy is serious business), years of disease-free life without the indefinite use of drugs is the stuff of most MSer’s dreams.

HSCT has been proven to work best on patients with very active inflammatory disease (those “properly selected patients” I keep talking about), meaning patients whose disease is marked by frequent relapses and enhancing lesions on their MRI images. Many if not most RRMS patients fall into this category, but unfortunately far fewer SPMS and PPMS patients fit the bill. Study after study (click here and here) has shown that the most important criteria for identifying patients on whom HSCT has the best chance of success is the presence of enhancing lesions as detected by MRI.

Enhancing lesions are a sign that the immune system is actively causing inflammation within a patient’s central nervous system, while the lack of enhancing lesions signals that the disease is being driven by some other, as yet undiscovered, mechanism. A comprehensive overview of HSCT results on MS patients worldwide conducted by Brazilian researchers came up with the following recommendations for selecting patients who might benefit from HSCT: “… the forms of the disease that might benefit from transplantation are: relapsing remitting, primary or secondary progressive, and the “malignant” form, provided there is evidence of inflammatory activity at the time of transplant indication.” These researchers further suggest that the treatment not be given to patients who have lost the ability to walk, with the exception of those suffering from extremely aggressive MS who have accumulated disability quickly. It’s also very important that patients be relatively healthy aside from their MS, hearty enough to withstand the rigors of a short burst of intense chemotherapy.

Unfortunately, as is illustrated by the above recommendations, many patients suffering from progressive MS are left holding the bag, as many SPMS patients and most PPMS patients don’t exhibit signs of active inflammatory disease (enhancing lesions), and thus likely would not be considered good candidates for HSCT. Eligibility for the treatment cannot be ascertained by disability levels alone, as the majority of PPMS patients never display signs of active inflammation (enhancing lesions) even when first presenting with the disease, when disability levels are in many cases barely detectable.

Throughout the world of MS research there is a growing recognition that early treatment is the key to reducing the impact of multiple sclerosis. In fact, many researchers and clinicians now talk of a window of opportunity before the disease becomes entrenched, when all treatment options have their best chance of success. This is the time when the immune system plays its most active role in the disease, and when enhancing lesions are most likely to be rampant. Because HSCT is not without risk and can be a difficult process to get through, it may be challenging for doctors and patients alike to be convinced that this treatment may be their best chance at diminishing the long-term physical impact of multiple sclerosis before that window of opportunity is missed. In fact, it may be a mindset that sees HSCT as too draconian that proves to be the biggest impediment to the widespread adoption of this therapeutic approach.

Despite the immense potential of HSCT, it’s important to understand at the deepest level that this is still an experimental treatment option. Although there is serious science backing the effectiveness of HSCT, protocols have yet to be completely standardized, best practices are still being ascertained, and large-scale trials are still underway (click here). HSCT has not been approved for the treatment of MS by any national or international regulatory body. Nevertheless, as might be expected, a medical tourism industry is springing up around HSCT, and more and more patients are traveling to different locations around the world to undergo the procedure. Websites and Facebook pages about HSCT are proliferating, with some spreading what at best be termed low-grade information. There is a wealth of anecdotal evidence in the form of legitimate patient testimonials confirming the effectiveness of the treatment (click here), but anecdotal evidence for any alternative treatment is almost always skewed heavily towards the positive (folks with negative experiences with such treatments, especially expensive ones, rarely post about them on the Internet), and more than a few of the Internet “resources” I’ve come across seem to be more marketing tools than reliable sources of actionable facts.

Therefore, it is absolutely essential that any patient considering HSCT educate themselves using the most scientifically legitimate resources available, and then educate themselves some more. One should never put complete trust in any patient driven source of info (this blog included), and special diligence should be taken when reading information supplied by companies and institutions offering, for a price, the treatment itself. Some of the best research papers I’ve read on HSCT can be found at the following links (click here, here, and here).

All of these caveats aside, Hematopoietic Stem Cell Transplantation could very well represent a major shift in the way MS is treated in the not-too-distant future, at least for a substantial subset of patients afflicted with the disease. HSCT is serious business, but so too is multiple sclerosis. Even though studies suggest that HSCT does not put a permanent stop to the disease (click here), the promise of many years of life free from any symptoms is enormously tantalizing, so much so that many patients are proving to be more than willing to take the plunge. One can only hope that as researchers perfect their skills and methodologies HSCT will become ever more safe and effective. While likely not the Holy Grail of a cure, HSCT could represent a significant step forward in treating this very ugly disease, albeit one that apparently and unfortunately has little to offer many of those most disabled by the illness, those stuck in the stranglehold of progressive MS whose disease is absent active inflammation.

The below video is a segment from the Australian version of the TV news magazine 60 Minutes, which traces an Aussie MS patient’s successful HSCT journey to Russia and back. Please note that this is not in any way an endorsement of the Russian clinic offering the treatment. In fact, as I was writing this article, news landed in my email inbox of a patient who died at this Moscow clinic while undergoing HSCT for the treatment of a rare disease called Stiff Person Syndrome (click here). Though the news states that HSCT was not necessarily the direct cause of her death, this should only emphasize the serious nature of this treatment regimen. Again, patient selection is the key ingredient to the success of this treatment. Patients must be physically strong enough to endure the taxing effects of the chemotherapy agents used during HSCT, the toxicity of which varies from treatment center to treatment center. One must guard against letting hope eclipse reason, but I know all too well that desperate times can call for desperate measures…

Stem Cell Treatments for Multiple Sclerosis

For patients, physicians, and researchers alike, stem cells hold the tantalizing potential of turning back the tide of multiple sclerosis, repairing damaged brains and spinal cords, and perhaps even offering something approaching a cure. There is plenty of hype surrounding stem cells, and they provide much reason for hope, but what is the reality of the current state of stem cell research for the treatment of MS?

As all patients with MS are aware, the currently available treatments do nothing to cure the disease or repair the damage that it does. At their best, today’s crop of disease modifying drugs (DMDs) quiet the disease, thereby improving the quality of life for many of the patients taking them, especially those suffering from relapsing remitting multiple sclerosis. However, many of these drugs carry with them risky side effect profiles, and though the newest compounds represent advances over their predecessors, patients are crying out for revolution, not evolution.

Stem cells could represent the revolution patients so fervently desire. Because of their ability to transform into almost any type of cell in the human body, stem cells may hold the key to achieving one of the holy grails of modern medicine, the regeneration and repair of damaged tissues. For MS patients, this could potentially mean the reversal of disability, and with it the long dreamt of disposal of wheelchairs, walkers, and canes. We are still a long way from that lofty goal, however, but the first few steps along the path to that salvation are currently being taken.

Though stem cell research is advancing in laboratories worldwide, the science of using stem cells to treat diseases in humans is still in its infancy. Because multiple sclerosis is a neurodegenerative disease, and its most prominent feature is the damage the disease does to the central nervous system, it is hoped that stem cells may hold the key to reversing the carnage wrought by the disease by facilitating the repair of damaged nerve cells. Furthermore, research has provided hints that stem cells may modulate the abnormal immune response seen in MS patients, and some researchers are even using stem cells to completely reboot the human immune system, a process that in some cases appears to stop the disease dead in its tracks.

It’s important to understand that there are two very different approaches to using stem cells in the treatment of multiple sclerosis. One approach hopes to use the cells to repair damaged nervous systems; the other uses stem cells to provide the patient with a brand-new immune system, one that theoretically will not turn against a patient’s own body. The latter approach is known as hematopoietic stem cell transplant, or HSCT, and has been used on patients in trial settings for almost two decades.

HSCT involves ablating (destroying) a patient’s existing immune system through the use of powerful chemotherapy drugs, and then intravenously infusing a patient’s own stem cells back into their body, a process depicted in the below diagram:

Once infused back into a patient’s body, the stem cells go about reconstituting their immune cells, effectively providing them with a brand-new immune system that in theory shouldn’t go to war against the patient’s own brain and spinal cord. In practice, this type of therapy has proven to be quite effective, particularly among patients with aggressive relapsing remitting disease who display a high amount of inflammation in their central nervous systems, as are evidenced by enhancing lesions seen on MRI imaging.

As you might imagine, using powerful chemotherapy drugs to destroy a patient’s immune system is not without its dangers, and early attempts at this therapy had mortality rates as high as 10%. As researchers perfected their methodology and began using less dangerous chemotherapy agents, though, the risks associated with HSCT dropped dramatically. Today, most patients undergoing HSCT are subjected to chemotherapy and immunosuppressive agents that do not completely destroy their bone marrow, and the safety profile of the procedure has improved impressively. The results achieved by this HSCT can be dramatic. In one study (click here) that looked at the long-term outcomes of HSCT, after 11 years 44% of patients who had started out with aggressive relapsing remitting disease were free from disability progression. By comparison, only 10% of those who did not display signs of active inflammation before HSCT remained stable.

One of the primary proponents of HSCT therapy for MS patients, Dr. Richard Burt of Northwestern University, stresses that the proper selection of patients is the key to the success of the treatment. In fact, the title of the paper he recently published (click here) includes the phrase “if no inflammation, no response”. “It’s the only therapy to date that has been shown to reverse neurologic deficits,” said Dr. Burt, “But you have to get the right group of patients.” In a study published by Dr. Burt in 2009, 17 out of 21 relapsing remitting patients improved after HSCT, and after three years all patients were free from progression (click here). Dr. Burt is currently heading up the HALT-MS trial for HSCT (click here). There are several centers around the world offering HSCT therapy, and there is a Worldwide HSCT Facebook group (click here) that contains information on all of the legitimate HSCT facilities worldwide. The group is populated by many folks who have undergone HSCT therapy. Be aware that it’s a private group, and you must request membership before being given access to all of the available information.

While HSCT holds much promise for putting the brakes on very aggressive relapsing remitting multiple sclerosis, it unfortunately has little to offer those with progressive disease, and does nothing to directly repair the damage done to the central nervous system by MS. Fortunately, another form of stem cell therapy proposes to do just that. Researchers in two centers in the US have received FDA approval to use bone marrow derived mesenchymal stem cells (MSCs) to repair nervous system damage, thereby possibly reversing the effects of the disease. There are additional trials using MSCs to treat MS underway internationally. Mesenchymal stem cells have the ability to transform (differentiate) into many different cell types, and could prove to be the building blocks necessary for repairing damage to the central nervous system as well as other organs and tissues. Experiments using MSCs to treat animal models of MS have been very encouraging (click here), demonstrating the cells’ abilities to modulate the immune system and spur the repair of damaged nervous system tissues. It remains to be seen whether the same effects can be achieved when using the cells to treat human beings.

The two FDA approved studies both use MSCs harvested from a patient’s own bone marrow, but employ them in very different ways. One study, currently underway at the Cleveland Clinic (click here), infuses mesenchymal stem cells intravenously into the patient, in the expectation that the cells will modulate the immune system and also initiate the regeneration of damaged tissues in the central nervous system. This study, which will eventually use MSCs to treat 24 patients, is proceeding slowly, but as the above linked to article details, one of the first patients treated is already reporting encouraging results.

The second FDA approved trial, to be conducted by the Tisch MS Research Center of New York (which just so happens to be my MS clinic), will use mesenchymal stem cells that have been transformed through a proprietary laboratory process into neural progenitor (NP) cells, injected directly into the spinal fluid (intrathecally)) of the patient (click here). Neural progenitor cells are a specialized type of stem cell specific to the nervous system that have the ability to transform into the various types of tissues damaged and destroyed by the MS disease process. Researchers at the Tisch Center have developed a way to get mesenchymal stem cells to differentiate into neural progenitor cells, and hope that by injecting these cells directly into the spinal fluid the NP cells will directly target the regenerative mechanisms of the central nervous system (click here). The stem cells themselves may act to repair damaged tissues, but they’ve also been shown to have the ability to recruit existing stem cells within the brain and spinal cord to jumpstart the body’s own repair mechanisms.

It’s important to remember that both of these studies represent a very different approach to stem cell therapy for MS than HSCT. The primary goal of HSCT is to reboot a patient’s immune system; HSCT does nothing to directly address the damage that has already been caused by the disease, but rather seeks to disrupt the disease process. Taking a different approach, the trials being conducted at the Cleveland Clinic and the Tisch MS Center seek to effect repairs on the damaged brains and spinal cords of MS patients, albeit through two different methodologies. HSCT and the reparative therapies being tested in the FDA trials have little in common other than the fact that they both use stem cells in an attempt to treat MS.

I’m sure that many patients reading this are aware that there are clinics in Central America, Asia, and Europe offering regenerative stem cell therapy to patients at hefty price tags. Some of these clinics aggressively market their services, and typically charge $20,000-$40,000 for a single round of stem cell therapy. Various Facebook pages, blogs, websites and posts on MS Internet forums extol the virtues of the treatments these clinics provide, often offering glowing testimonials from patients they have purportedly treated. Although I don’t want to disparage any patient relating their genuine experiences with these clinics, I’ve known several MSers that have traveled to a variety of these clinics and undergone stem cell treatments, and unfortunately none of them have experienced anything in the way of significant or lasting benefit.

I would caution anybody considering treatment in Panama, Costa Rica, Germany, India, or any of the other clinics offering stem cell therapy without any published scientific proof of the effectiveness of their treatments to think long and hard before committing substantial amounts of money for a therapy that, according to the experiences of people that I actually know, has very little chance of working. The two legitimate trials I outlined above both involve multiple treatments given over an extended period of time, using cells that have undergone lengthy (months long) processes of multiplication and/or differentiation in the laboratory before being transplanted back into the patient. Such regimens are not followed by the “pay to play” clinics; instead, they generally infuse stem cells back into the patient soon after they are harvested, and offer extremely limited, if any, follow-up care.

Additionally, some of these clinics don’t use a patient’s own stem cells for treatment, but rather umbilical cord cells, on which far less research has been done. The use of stem cells not derived from the patient themselves opens up all kinds of questions regarding safety and efficacy, as the cells are genetically different from the tissues they are meant to repair. If any of these clinics regularly achieved anything close to the number of successful outcomes that they claim, they would surely publish their results in legitimate scientific journals and reap the personal and professional accolades that would follow. Can you say Nobel Prize? Instead, they publish marketing materials and partner with travel agencies. Reason enough for skepticism. In short, let the buyer beware.

Stem cell therapy holds tremendous potential for the treatment of multiple sclerosis, and provides much reason for hope. The efficacy of HSCT for treating very aggressive relapsing remitting multiple sclerosis is well documented, and the safety of this treatment regimen has increased dramatically as practitioners have perfected the process. Regenerative stem cell therapy, of the type currently being trialed at the Cleveland Clinic and Tisch MS Research Center of New York, is still in its infancy, but is bursting with promise, possibly holding the key to repairing the damage done by multiple sclerosis and restoring function robbed by the disease. As with all new therapies, though, it is vitally important to not let hope eclipse reason, or let hype cloud judgment. We are at the dawn of a new age, and I fully believe that the use of stem cells will revolutionize the practice of medicine. Research into the use of stem cells to treat MS is quickly picking up steam, and in combination with other emerging therapies, rays of hope are finally being shone upon the disease and those afflicted with it. It’s about time, don’t you think?