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)…

Research Roundup: CCSVI, New Drugs, and Other Items of MS Interest

The last two months have brought a deluge of MS research data, much of it coming out of October's ECTRIMS (European Council on Treatment and Research in Multiple Sclerosis) conference, this year held in Amsterdam. While the meeting was dominated by the release of drug study data (naturally), there was also tantalizing research data revealed regarding CCSVI as well as a number of other MS related matters. I'll attempt to provide a broad overview of the recent research goings-on, and will try my best to not put readers to sleep with too much scientific mumbo-jumbo. Just in case, better grab a blanket and a pillow, because I have a feeling this is going to be long…

♦ CCSVI - On the CCSVI front, ECTRIMS appears to have been the latest venue for the ongoing pissing war that's being waged between CCSVI supporters and detractors, featuring dueling research reports, most of which are entirely based on imaging studies finding greater or lesser degrees of venous abnormalities in MS patients. To my mind, the problem with all of these studies, both pro and con, is that the imaging techniques used (MRVs and Doppler sonography) are prone to technical and/or operator error, so the wide disparity in findings may more reflect the failings of the technology then the hypothesis being explored. MRVs are highly subject to artifacting, and sonography is extremely operator dependent. While time and experience has brought more accuracy to both technologies in regards to revealing CCSVI, the fact remains that the only way to assess the state of a patient's veins with a high degree of accuracy is to actually go in and explore those vessels with an invasive (minimally) catheter venography, which so far has proved impractical for large-scale study purposes, especially when it comes to subjecting healthy subjects to a potentially (again, minimally) risky procedure.

While quite a few studies were presented that refute the theory that multiple sclerosis has a vascular component (click here), some others provided intriguing finds that support the CCSVI hypothesis. The most striking of these was a small study out of the esteemed Cleveland Clinic that compared jugular and azygos veins taken postmortem from the cadavers of MS patients and healthy control subjects. This of course begs the question, can a cadaver truly be a healthy control subject? Certainly, healthy though they might once have been, at the very least they'd be terrible guests at dinner parties. But I digress… The unique aspect of this study is that investigators were actually able to hold and examine the veins in question, the only imaging technology utilized being the ever trusty human eye (presumably aided by some type of optical magnification).

Although quite small, limited to only 13 subjects, the study hints at some rather dramatic trends (click here). The researchers looked at the veins of 7 MS and 6 non-MS subjects, and found a variety of structural abnormalities and anatomic variations. Interestingly, vein wall stenosis (narrowing) occurred in equal numbers among the MS and non-MS samples. More prevalent in the MS veins, though, were abnormalities involving malformed valves and anomalous membranes (structures such as webs and septums that shouldn't be there) which could lead to disrupted blood flow. These types of abnormalities would be difficult to spot using noninvasive imaging methods, casting further doubt on studies reliant strictly on traditional MRV in particular, and also Doppler sonography unless the operators were well-versed in protocols specifically designed reveal such anatomic irregularities.

The findings of this study, if borne out by future, larger investigations, could shed light on the wide disparity in benefit (or, often, lack of benefit) experienced by those who have undergone CCSVI venoplasty (click here for a terrific discussion of this, written by Julie Stachowiak of about.com). Many CCSVI treatment procedures, especially those done within the first year or so after knowledge of CCSVI hit the mainstream MS population, concentrated primarily on areas of venous narrowing, which the Cleveland Clinic findings suggest are not as abnormal as first thought. Since these narrowings were seen in equal numbers among MS and non-MS subjects, they may fall within the parameters of normal anatomic variation, and have little actual significance.

The high prevalence of malformed or misplaced valves and other anatomic structures within the veins of MS patients, on the other hand, could very well prove to have considerable import. Although the goal of CCSVI treatment has in large part shifted away from simply expanding narrowed veins and moved more towards clearing malformed or otherwise broken valves, aberrant membranes  would in many cases be difficult to treat using the balloon venoplasty techniques currently employed to address CCSVI. In theory, some of these treatments may have coincidentally alleviated the effects of such abnormal membranes by disrupting them and compressing them against the vein walls of treated patients. If this were the case, and these membranes eventually returned to their original form, this might explain the far too common phenomenon of restenosis experienced by patients treated for CCSVI. The failure to properly treat malformed valves and abnormal and misplaced membranes within the veins might also explain the failure of CCSVI treatment to significantly benefit many of those who have undergone treatment. This of course assumes that the MS-CCSVI link exists, which despite a growing body of anecdotal evidence, still needs to be confirmed by scientifically robust studies.

The Cleveland Clinic cadaver study certainly illustrates how little we still actually know about CCSVI and the proper way to treat it, and that some of the initial assumptions upon which treatment methodologies were based might have been misguided. Certainly, should CCSVI prove to be a vital piece of the MS puzzle, CCSVI venoplasty techniques must be refined, and very likely equipment and devices specifically designed to treat the condition effectively need to be developed and put on the market. As I've mentioned in previous posts, the study and treatment of CCSVI is still in its infancy, and patients and physicians alike need to be careful not to put the cart before the horse, despite the tremendous amount of hope and excitement that CCSVI has generated.

Another interesting CCSVI research project, conducted by the Buffalo Neuroimaging Analysis Center (BNAC) looked at the phenomenon of CCSVI in healthy patients, and attempted to identify risk factors that might be involved in the development of the condition (click here). BNAC has imaged hundreds of MS patients and healthy controls, and found that CCSVI is present in roughly 25% of non-MS subjects. By pinpointing the factors that might lead to the development of CCSVI in otherwise healthy people and cross-referencing these with known risk factors for MS, the relationship between CCSVI and MS might better be assessed.

Since a picture is said to be worth a thousand words, I suppose a video made up of moving pictures would be worth several million words, so, in the interest of saving you pages and pages of reading, here is the head researcher at BNAC, Dr. Robert Zivadinov, discussing the results of this study:






Indeed, the findings of this study are fascinating, in that many of the known risk factors of MS (particularly infection with the Epstein-Barr virus) also seem to be prevalent in healthy subjects who exhibit CCSVI when subjected to noninvasive imaging techniques. As Dr. Zivadinov stated, study findings such as these only emphasize the need for continued, multidisciplinary research into the CCSVI-MS connection. My e-mail inbox sees a steady flow of notes from patients who have benefited from CCSVI treatment, but also a disturbingly high number of reports from patients disappointed in the lack of results they've experienced. The CCSVI story has only started to be written, and with more research results set to be released in the coming months, our knowledge of the condition should expand exponentially.

Perhaps the most well-known MS sufferer to undergo CCSVI treatment is Montel Williams, who recently discussed his experience in this video with the celebrity physician Dr. Oz. Unfortunately, Dr. Oz gets some of the particulars about CCSVI treatment wrong, but there certainly is value in Montel's testimony. Here is Montel's story, in his own words:





♦ Pharmaceuticals -some late stage MS drug trial results have been released recently, most describing extremely positive results. Disparaging Big Pharma is a favorite pastime of mine, and I think the pharmaceutical companies deserve all the disparaging they can get, due to their sometimes devious and deceitful ways of doing business, and their iron grip on most of the medical research that takes place in the USA. Unlike some other MS advocates, though, who disparage all Big Pharma MS products as snake oil, I've come to realize the value of the ever-expanding arsenal of disease modifying drugs. Though none of them offers anything close to a cure, for those patients who find them effective, they do increase quality of life, sometimes dramatically so. Of course, many of them do come with a laundry list of frightening potential side effects, but by reducing relapse rates and in some cases alleviating the burdens of disability, the current crop of disease modifying drugs has been a godsend to the patients on whom they are effective. Hopefully some of the newer compounds on the horizon will be all the more effective while at the same time limiting deleterious side effects.

One of the most promising new compounds is BG 12, an oral MS drug being developed by Biogen. Also known as oral fumarate, BG 12 has been shown in late stage phase 3 trials to not only dramatically decrease relapse rates and the number of lesions seen in the MRIs of treated patients, but also appears to significantly delay the progression of the disease in some patients (click here). Research results showed that BG 12 reduced relapse rates by 50% when compared to placebo, and also reduced the risk of disease progression by 38% over placebo. The drug works in a way very different than any existing MS medication, by suppressing pro-inflammatory factors called cytokines, and possibly providing some protection against nerve cell death. Encouragingly, the drug also appears to have a very benign side effect profile, with the most common side effects being gastric disturbances and diarrhea. The drug does not appear to open patients up to opportunistic infections or cancers, as do some of the other available MS pharmaceutical therapies. Given that BG 12 is an oral drug that seems to be very effective, and carries with it a relatively benign side effect profile, I expect this drug may prove to be very popular with patients and the doctors who treat them.

Genzyme announced the results of phase 3 trials of the drug Alemtuzumab, which was previously known as Campath and will be marketed under the name Lemtrada (click here). This very powerful drug is given intravenously, with infusions once a day for 5 consecutive days for the first treatment and then, a year later, 3 infusions during 3 consecutive days. Lemtrada severely depletes the human immune system, acting on both lymphocytes and monocytes, which are then reconstituted by the body, resulting in permanent changes in the immune systems of patients treated with the drug. In effect, Lemtrada "reboots" the immune system, in the hopes that the reconstituted immune system will no longer attack a patient's own nerve cells. Trial results showed Lemtrada to reduce relapse rates by 49% when compared to patients taking Rebif, along with a 42 percent reduction in the risk of sustained accumulation (worsening) of disability as measured by the Expanded Disability Status Scale (EDSS). Previous trials have shown that the effects of Lemtrada are very long-lasting, with patients showing significant benefit five years after initial treatment ended (click here). However, while these results are very impressive, Lemtrada does carry with it the risk of some serious side effects. About 16 % of treated patients develop autoimmune thyroid disease, and 1% develop a potentially lethal autoimmune blood disorder known as ITP. Because of this, patients using the drug must be carefully monitored, and use of Lemtrada may be limited to patients with highly active disease. Research is currently underway to develop ways to identify patients most at risk for the autoimmune side effects of Lemtrada, to more easily identify patients who should be excluded from this treatment option (click here).

The potential MS vaccine Tovaxin has been granted fast-track status for the treatment of SPMS by the FDA (click here). Fast-track status can cut in half the time it takes a drug to be approved, and if Tovaxin does eventually get such an approval, it will only be the second drug specifically approved for the treatment of secondary progressive multiple sclerosis in the United States. Tovaxin is a compound individualized for each patient, which desensitizes a treated patients immune system T cells to their own nerve cells, thereby stopping the autoimmune reaction (click here). Several years ago, Tovaxin failed to meet the goals of its phase 2 trials (click here), and although it had shown great promise, was left for dead. The company developing it, Opexa, later re-examined the failed trial data and determined that Tovaxin had indeed demonstrated positive effect, and now Tovaxin has risen like Lazarus, giving it (and Opexa's stockholders) new life…

A study done to assess the risk of stopping Tysabri for "drug holidays" showed that this practice significantly increases the risk of patients suffering MS relapses within six months after stoppage (click here). The idea of drug holidays came about because Tysabri is linked with PML, a potentially fatal brain infection, the risk of which increases with the amount of time a patient is on Tysabri. It was thought that taking occasional breaks from Tysabri might allow the immune system to reconstitute itself enough to combat the emergence of PML, but this study suggests that temporarily switching to another MS therapy unfortunately carries with it an increased risk of patients suffering an MS relapse. Kind of a "damned if you do, damned if you don't" scenario…

♦ Miscellaneous Studies - A variety of other MS related research results have also recently been announced. The active ingredient in the spice saffron may prove to be effective in combating MS (click here). In experiments, this ingredient was shown to combat inflammation and cell stress, at least in petri dishes and test tubes. Interestingly, saffron is often used in Asian cuisines, and the incidence of MS is much lower in Asian countries than it is here in the West. The spice tumeric (cumin) has also been shown to have strong anti-inflammatory properties, and this spice too is used heavily in some Asian cuisines. So go out and have some Indian food, it's good for you. Chicken Tikka Masala, yum…

Researchers in Sweden have discovered that young people between the ages of 16 and 20 who work overnight shifts or odd hours are twice as likely to develop multiple sclerosis as those who never worked such hours (click here). The researchers explained the sleep restriction associated with working the night shift has already been shown to increase the risk for certain health problems, including heart disease, thyroid disorders and cancer, likely by interfering with melatonin secretion and increasing inflammatory responses. Kind of an odd finding, but upsetting circadian rhythms has been shown to have an adverse effect on health, so these Swedish meatballs might be on to something…

German researchers have linked gut bacteria to multiple sclerosis (click here). We all have millions of microbes living in our guts, normally to no ill effect. However, more and more research links these bacteria to some autoimmune diseases. The researchers who did this study used mice genetically engineered to develop a Multiple Sclerosis like disease, and allowed some to develop gut bacteria, and others to remain gut microbe free. About 80% of the mice with gut bacteria went on to develop MS like symptoms, while none of the sterile mice did. While it's a far cry to go from mice to humans, this study does demonstrate that intestinal microbes do interact with the immune system, something that has long been suspected. Of course, most of the bacteria are in our guts is harmless, and some even serve a beneficial effect, but these research results certainly warrant further investigation.

Well, let's call it a wrap. There's an astounding amount of MS research being conducted, much of it driven by the huge profits to be made treating MS patients with hyper expensive drugs that tamper with the little understood human immune system. Still, as is evidenced by the last few investigations I mentioned, the breadth of MS research is quite wide, and each bit of knowledge uncovered may hold the key that finally unlocks the puzzle that is MS. Certainly, research into CCSVI has the potential to upend much of the conventional wisdom regarding the disease, and it's of the utmost importance that MS patients themselves drive such research forward, by educating themselves, advocating for energetic and innovative research into the disease, and agitating against those who stand in the way. Power to the people, y'all…

Related articles

• Risk Factors For CCSVI Are Similar To Risk Factors For Developing MS (medicalnewstoday.com)

Bits and Pieces: End of Summer Edition

Image by Claudio.Ar via Flickr

Well, here's another collection of various items of interest (well, at least of my interest), most of which have something to do with MS, and none of which have anything to do with the end of summer. Just thought I'd note that the seasons have changed once again, and we are now officially in autumn, my favorite time of year.

Time just whizzes by, doesn't it? I've noticed that the older you get, the faster time seems to pass, so much so that it becomes increasingly difficult to get your arms around the quickly passing days, and events unfold at breakneck speed. Remember when the two-month summer vacation from grade school seemed like an eternity, filled with innumerable dramas and intricate subplots? Now two months seem to pass in the time it takes me to let out a good yawn.

Just goes to show how subjective is our existence. I suppose this ever increasing sense that time is speeding up has something to do with the fact that as we get older, each increment of time becomes a lesser part of our lives. For example, a two-day-old infant experiences a single day as 1/2 their lives, whereas, at 48 years old, a single day represents 1/17520 of my existence. All the more reason to try to make the most of your remaining time on earth, and here I've gone and completely wasted about a minute of your precious, ever dwindling allotment of life. Please forgive me.

With that, my latest collection of flotsam and jetsam…

♦ Researchers have discovered that the brains of MS patients show a marked deficiency in substances known as Neuro-Steroids (click here). Neuro-Steroids help build brain cells and maintain their function, thus increasing their levels in patients deficient in them might not only stop MS in its tracks, but also actually repair some of the damage that the disease does to the central nervous system. Better still, drugs designed to increase the level of Neuro-Steroids are already being trialed for use in combating epilepsy and depression, meaning that, if successful, Neuro-Steroid drugs could be on the market much quicker than a newly discovered compound that has yet to hit the trial pipeline. Of course, this research is still in its early stages, but it does seem quite promising.

♦ In other drug-related news, researchers have figured out a way to deliver drugs across the blood brain barrier, an obstacle that has inhibited the treatment of many central nervous system diseases throughout the history of medicine (click here). The blood brain barrier functions to keep the brain and spinal cord out of harm’s way by carefully selecting just what substances can cross from the bloodstream into the CNS, much like the doorman at an exclusive nightclub picks and chooses amongst the riffraff clamoring to get in, only allowing entry to the anointed few deemed worthy of such a privilege, a practice that made me want to vomit even back in the glory days when I was "fortunate" enough to be one of those deemed worthy. Anyway, researchers have now figured out a way to open a temporary window in the blood brain barrier, potentially paving the way for a new level of efficiency in treatments designed specifically for central nervous system disorders.

♦ Researchers in Japan have discovered a high-tech method of analyzing cerebral spinal fluid (CSF), allowing for the differentiation between MS and other neurologic diseases (click here). This could be hugely important, as currently there is no test specific for MS, making it a diagnosis by exclusion. In other words, doctors diagnose MS primarily by eliminating other possible causes of a patient's symptoms and diagnostic test results, a process which results in a fairly wide margin of error and a misdiagnosis rate of about 5%-10% . That's right, for every 10 people reading these words, there's a good chance that one of you has been misdiagnosed. So put that in your pipe and smoke it.

♦ A bit of bad news, as simvastatin (otherwise known as Zocor) has been found to be ineffective as a treatment for MS (click here). Four or five years ago there was much buzz about the statin drugs (commonly used to treat high cholesterol) possibly being of use in the treatment of MS, potentially as an add-on to be used in addition to other therapies, but recent research results have been disappointing.

♦ In CCSVI related news, the Buffalo Neuroimaging Analysis Center (BNAC) published a comprehensive overview of all of the CCSVI research that has been done to date. The BNAC Patient Advisory Council, of which I am part, put together an easy-to-read digest distilled from the much longer piece, written specifically with patient education in mind (click here). It's done in a question-and-answer format, and should provide a nice overview of the current state of CCSVI knowledge.

♦ The Canadian province of Saskatchewan this week announced that it will be sending MS patients to Albany, New York to participate in a CCSVI treatment clinical trial (click here). Although CCSVI research is not moving along as fast as many of us wish it would, in actuality the pace of research is quickening and gaining momentum, and hopefully we will soon start to reap the benefits of that research.There is still far more about CCSVI that we don't know than we do, and getting those questions answered, dither pro or con, in the quickest possible fashion is in the best interests of all, regardless of their stance on the hypothesis.

♦ For those interested in a comprehensive and extremely well researched and well-written account of the history of the CCSVI hypothesis and the science behind it, a terrific resource is the book "CCSVI As the Cause of Multiple Sclerosis" (click here), written by Marie Rhodes, a nurse and MS patient who was at the forefront of the CCSVI movement when it was in its early infancy. The book offers a wealth of knowledge, and is even available in a Kindle version.

♦ The Multiple Sclerosis Association of America (MSAA), a terrific organization that does much to aid MS patients, is offering a couple of interesting programs that caught my eye. The first is a webinar series designed to instruct patients on taking care of their financial well-being (click here), an incredibly important topic given the fact that so many of us are either already on disability or are contemplating a potentially financially treacherous future out of the workplace. The first webinar, "Being Money Smart", is scheduled for October 6, so sign up now!

The second program is the MSAA's Annual Art Showcase, which is now accepting submissions (click here). This year's theme is "Change", and artists are encouraged to interpret this theme as creatively and broadly as they wish. The showcase is limited to two dimensional art, and doesn't include photography (boo!).

♦ For those interested in the alternative treatment Low Dose Naltrexone (LDN), Julie Stachowiak, who writes About.com's invaluable weekly column on MS, has been keeping a diary of her recent foray into the world of LDN (click here). Naltrexone is an old drug that is used to treat various addictions, but in very low doses it has been purported to alleviate the symptoms of MS and a variety of other diseases. Anecdotal accounts seem very encouraging, with many patients reporting significant improvements while taking LDN. I tried LDN early on in my MS adventures, but found it didn't do anything for me. Of course, I'm not the best example to go by, since my diagnosis is quite uncertain (click here).

Unfortunately, because Naltrexone is an off patent drug it's cheap and there's not much money to be made from it, so very few if any scientifically valid clinical trials have been done to test its efficacy on MS patients. Just another of the many travesties visited upon chronically ill patients worldwide by a medical research system driven more by the quest for profit than by the desire to alleviate the misery of millions. Harrumph.

♦ Researchers in Scotland have found that marriage between cousins is not to blame for the high rate of MS found in that region (click here). Scotland has one of the highest rates of MS in the world, approximately 1 in 500, and the islands in which the study was conducted, Orkney and Shetland, have rates higher still. Far be it for me to cast judgment, so all I'll say to those contemplating marrying a close relative is that you can put any fears about your future children being predisposed to developing MS to rest. As for fears about extra limbs, or eyeballs in the middle of their foreheads, well, that's another story…

♦ In a sad bit of news, a lion suffering from Multiple Sclerosis like symptoms in Brazil died this past July (click here). Apparently, the plight of Ariel the lion touched the hearts of many, and his story was chronicled on his own website and Facebook page. Since I believe in a just universe, I'd like to think that Ariel is now in lion heaven, where he is using his fully functional claws, paws, and powerful legs to viciously maul and tear to pieces all of the naughty wildebeests and zebras who were sent to wildebeest and zebra hell. For everything, there is a season…

As Porky the Pig might say, th-th-th-that's all folks…

Pieces and Bits

I'm getting tired of titling posts "Bits and Pieces", so I cleverly changed things up this time around. Don't be too rattled, though, what follows is still a collection of MS related items that I thought you might find useful and/or interesting...

Image by hitthatswitch via Flickr

• How effective are the CRAB (Copaxone, Rebif, Avonex, and Betaseron) drugs at slowing down the progression of disability in MS patients? Not very, according to some recently published studies. A paper analyzing these results has been making the rounds of the Internet forums for the past week (click here for paper), and the conclusion is that these widely prescribed and very expensive drugs do practically nothing to halt disability progression in the Multiple Sclerosis. The paper does a wonderful job at analyzing this very disappointing data, but I have to respectfully disagree with several of the conclusions it draws from this information. Written by Ashton Embry, who administers the excellent alternative MS site "Direct-MS" (click here) which contains very good information on the role of nutrition in the battle against MS, the paper draws the conclusion that the CRAB drugs are no better than snake oil in treating MS. While the new data suggests that these drugs don't stop the inexorable march of disability in MS patients, the drugs have been shown in clinical studies to cut down on the number of relapses and enhancing lesions (as seen in MRIs) experienced by the MS patients taking them. When these drugs were first approved, the assumption was that a reduction in relapse rate and lesion load would translate into a significant delay in disease progression. While it is a crushing disappointment that the CRABs most likely do not slow progression, to say they are worthless overstates things a bit. The fact is, they do reduce relapse rates for some taking them, which does improve the quality of life for patients with Relapsing Remitting Multiple Sclerosis. Although an improvement in quality of life might be less than what was hoped for, it is still of considerable benefit to those afflicted with the disease. Certainly, the drugs have been overhyped, and overpriced, but patients who had been experiencing four or five relapses a year before being put on one of the CRABs, and only one or two after, would argue that their taking the drug has not been without value.

  The fact that research is now showing the CRAB drugs to be of limited, if any, value in halting or even delaying disease progression points to the abject failure of putting MS into a box marked "autoimmune". Countless millions of dollars have been spent developing and marketing these drugs, and billions upon billions of dollars have been made selling them to the captive audience that is the Multiple Sclerosis patient population. The CRAB drugs have been a tremendous boon both to pharmaceutical companies and to the practices of MS specialists, but this latest data highlights the fact that they are only sophisticated mechanisms for symptom management, and that the years spent searching for compounds to better tinker with the human immune system have taken the eye of medical research off of its rightful target, which should have been the search for the root cause of the autoimmune reaction. The concept of autoimmunity has managed to turn MS into a multibillion dollar a year industry, and yes, the drugs that have been developed with that concept in mind have been of some relief to some MS patients. One can only imagine, though, that if the same time, money, and energy had been put into searching for that which causes our immune systems to go awry, we'd be much farther along in our quest for a cure to the scourge that we call MS.

  Let me state unequivocally that I am a CCSVI advocate who believes that the hypothesis should be researched as vigorously and as quickly as possible. The recent data regarding the ineffectiveness of the CRAB drugs in combating disease progression makes CCSVI research all the more imperative, and should fuel the clamor of MS patients worldwide to have their voices heard. We need treatment studies, and we need them now. If such studies should by chance disprove the CCSVI hypothesis, then so be it. At least the effort will have been expended in a noble effort to free MS patients from their disease, rather than consign them to a lifetime of indentured servitude to drugs of only marginal effectiveness.

• MS is a notoriously hard disease to diagnose, the diagnostic process being one of exclusion, meaning that other possible conditions must be ruled out before a firm diagnosis of MS can be established. My own diagnosis has been seriously called into question, and there is disagreement between the doctors who have examined me at the National Institutes of Health and my personal neurologist over just what it is that is slowly crippling me. I've been questioning my diagnosis almost from the day I received it; my symptoms and disease course just didn't seem to match what I'd read about Primary Progressive Multiple Sclerosis and the experiences of others suffering from the disease. Studies have shown that between 5% -15% of those diagnosed with Multiple Sclerosis have been misdiagnosed, and are actually suffering from some other illness. Here's a paper (click here) that details the conditions that can be mistaken for MS, and includes a list of 100 such diseases. It's easy to make yourself crazy with information such as this (and believe me, I speak from experience), so be careful not to let this create doubt where there should be none, but if you have serious questions regarding your diagnosis, this paper is an invaluable resource. Knowledge is power, but be sure to wield it wisely.

• Multiple Sclerosis Dreams (click here for website) is a new organization designed to bring hope and excitement to patients living with MS. Similar to the Make a Wish Foundation, MS Dreams is a nonprofit organization that will be granting the dreams and wishes of desperate and needy MS sufferers of any age. Such dreams might include sending them on the vacation a lifetime, meeting someone they've found inspirational, or supplying them with much-needed treatments or devices. The organization will be in the running for a "Pepsi Refresh" grant of $25,000, which you can help them achieve by voting for MS dreams once the internet polls open on August 1. Although a new organization, its organizers seem extremely sincere and devoted, and I wish them the best of luck in launching their endeavor. So, please visit their website, and vote early and vote often...

• Researchers at UCLA have found a possible physiological cause for the depression often suffered by MS patients (click here for info). As if dealing with MS and its associated crap isn't depressing enough, it now appears that the disease causes atrophy of the hippocampus, a region of the brain closely associated with depression. MRIs have revealed that MS causes gray matter atrophy in general, so I suppose findings like this shouldn't be all that unexpected. A more momentous finding would be identifying what causes such atrophy, and may I suggest that decreased blood flow through the brain, such as might be seen in a vascular condition like, say, CCSVI, might be a pretty good candidate.

  Of course, zombies also have an appetite for gray matter, but I don't think I've ever seen a paper linking zombies with depression or MS. As a matter of fact, a good zombie movie often cheers me up, so I'm willing to go on record right here and right now stating that zombies do not cause MS. Then again, no zombie flick I've ever seen really identifies exactly what causes zombie-ism, so I guess it can’t be ruled out that MS causes zombies. So be careful during your next visit to the neurologist's office, you never know when one of your fellow patients may try to take a bite out of you.

Well, not the most uplifting collection of information I've ever presented, so let me leave you all with cheerfully healing thoughts of puppy dogs, rainbows, pretty ponies, and...

zombies zombies zombies. It's fun to say "zombie". (Don't forget, I dictate these posts using voice recognition software...)

Some Revised Thoughts on the Current State of CCSVI

Last week, I published a post on my thoughts regarding the current state of CCSVI research and treatment (click here). The post elicited much response, and many well thought out comments were left by readers who both agreed and disagreed with my points of view. As I've stated before, I welcome all readers to post their opinions, as a healthy exchange of ideas is the only way to draw informed conclusions, especially on subjects as new and controversial as CCSVI.

After reading and considering many of the responses arguing that research into whether or not venous blockages correlate with MS, and, if so, whether these abnormalities are cause or effect, were basically a waste of time and that treatment studies should take the forefront, I've changed my original point of view. While I still do think that academic research into the venous abnormalities we've come to call CCSVI is important, I now believe that treatment studies should be given the highest priority possible.

I've come to this conclusion for a variety of reasons. First, treatment studies themselves will show whether or not CCSVI abnormalities are indeed related to MS, and if they play a role in causing or exacerbating the disease. If, under rigorous trial conditions which include pre-and post-procedure neurologic evaluations, patients are found to respond favorably to the liberation procedure, then obviously CCSVI is not only related to MS, but plays an important role in the disease process. If patients fail to respond, then the opposite conclusions can be drawn.

Second, the noninvasive imaging techniques used to detect CCSVI have been shown to be less than reliable, and catheter venography has thus far proven to be the gold standard in finding blockages in the veins associated with the central nervous system. Based on the accounts of both the physicians who have performed the procedures, and patients themselves, Doppler sonography, MRV's, and CT venograms have all been shown to be prone to both false positives and false negatives when compared to the findings of catheter procedures, for a variety of reasons (technological limitations, operator deficiencies, etc.). Thus, any studies based strictly on noninvasive imaging will always have a cloud of doubt hovering over them. Better to cut to the chase, and perform catheter venography on test subjects. If that venography detects abnormalities, these abnormalities should be addressed by balloon angioplasty, which has been shown to be an extremely safe procedure when done by experienced physicians. Again, whether or not patients respond to angioplasty would answer questions of correlation and causation.

Third, if CCSVI does indeed prove to be a major piece of the MS puzzle, we need to refine the techniques and technology of the liberation procedure. Currently, many patients experience improvements soon after undergoing the procedure, only to see those improvements dissipate when their newly opened veins close up again. This phenomenon itself would suggest that CCSVI at least plays a role in the MS disease process, and also indicates that much learning needs to be done about the best practices, procedures, and equipment to be used when undertaking the liberation procedure. Virtually all of the medical equipment currently used in the treatment of CCSVI was developed primarily for use in arteries, which are vastly different in an anatomical sense to veins. Vein specific equipment, especially stents, needs to be developed if the liberation procedure does prove to be a major player in the treatment of Multiple Sclerosis.

Several other concerns have recently come to my attention. It seems to be becoming clearer that CCSVI is likely not just confined to the jugular and azygous veins, as has been thus far thought; the picture appears to be more complex. Dr. Zamboni has recently suggested that abnormalities in the lumbar veins could very well play a major role in progressive illness, and many venograms are finding abnormalities in the vertebral veins as well. The vertebrals are the vessels that return blood to the heart and lungs from the brain when patients are in an upright position. The jugulars take over this function when patients are lying flat. Thus, problems in the vertebrals could theoretically play just as important a role as jugular abnormalities. In my particular case, the catheter venogram done during my unsuccessful liberation procedure turned up blockages not only in my right internal jugular, but also abnormalities in my vertebral veins as well. Unfortunately, there is currently no accepted method for addressing stenosis in either the vertebral or lumbar vessels. Clearly, research into these concerns is necessary.

We must see collaboration between neurologists and vascular specialists if the myriad questions surrounding CCSVI are to be answered in any definitive fashion. I'm aware of several treatment studies that are currently awaiting approval, and of several doctors who are chomping on the bit waiting to get started conducting these trials. They'll have no problem finding patients willing to participate in these studies, but funding may be a dilemma. The MS patient population must get behind the studies, not only in body and spirit, but with their wallets too. When these studies are finally approved and announced, CCSVI advocates the world over, and those who love them, will need to step up to the plate and donate either directly to the institutions conducting the studies, or to nonprofit CCSVI advocacy groups that are currently readying to launch. Patient advocacy has pushed CCSVI out of the shadows and into the spotlight that currently shines on it, and that same advocacy will likely be necessary to take CCSVI from hypothesis to either positive or negative conclusion.

The CCSVI studies recently approved by the MS Societies of the United States and Canada will provide valuable data in assessing many of the questions that CCSVI theory has posed. I'm particularly intrigued by the study that will look at sets of twins in which one has has developed MS but the other has not. In fact, all of the approved studies will add greatly to the CCSVI knowledge base. But for a patient population desperate for answers, suffering with a disease in which time itself is an enemy, answering academic questions simply isn't enough. We must find out, as quickly and definitively as possible, whether or not the liberation procedure is as beneficial to some MS patients as anecdotal reports make it appear to be. Desperate times call for desperate measures, and for many MS patients, myself included, these are indeed desperate times...

Some Thoughts on the Current State of CCSVI

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Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning.

-Sir Winston Churchill, November 1942

It's now been almost 13 months since I first posted information on CCSVI, in a piece titled "Is MS Actually a Vascular Disease?" (click here). At that time, CCSVI was hardly a blip on the MS radar screen, knowledge of it confined mostly to a few dozen patients fervently researching and discussing Dr. Zamboni's findings on the patient forums at ThisisMS.com. A small handful of MS patients had been treated by Dr. Michael Dake, at Stanford University, having stents placed in the narrowings (stenosis) found in the veins associated with their central nervous systems.

Well, what a difference a year has made. CCSVI has created a firestorm in the MS community, as desperate patients have embraced the theory as their best hope to beat back this horrifying beast we call Multiple Sclerosis. Canadian television has aired numerous news pieces detailing the theory and the "liberation procedure" used to treat it (click here), hundreds of patients have been treated for the condition at locations scattered around the world, and the Internet is full of seemingly miraculous before and after videos portraying patients whose MS symptoms have dramatically declined after undergoing endovascular procedures to address their vascular abnormalities (click here). Just this past Thursday, the US and Canadian MS societies announced $2.4 million in grants to fund seven trials designed to test the validity of the CCSVI theory (click here).

Still, there is widespread disgruntlement among the MS patient population, many of whom are dismayed at the almost complete lack of treatment options available locally in the US and Canada, feel that research is moving much too slowly, and in fact believe that a conspiratorial cabal of pharmaceutical companies, mainstream neurologists, and MS societies is intent on suppressing and killing the CCSVI theory in order to protect huge profits and rapaciously defended spheres of influence.

I understand the desperation and anger these patients feel, which speaks loudly not only of the promise of CCSVI, but also of the failure of mainstream neurology to come up with any options better than simply suppressing or modifying our immune systems, often with drugs that carry with them the possibility of terrifying side effects. We are told that our immune systems have somehow gone bonkers and decided to attack our own tissues, but we've never been told why, and with the tremendous profits being generated by drugs companies marketing drugs targeted at the immune system, that why has been left to dangle in the air, twisting in the breeze. CCSVI appears to answer that vital why, in a fairly elegant and easy to understand manner, and thus has been embraced by a patient population frantic for answers.

It's important, though, to take a step back and calmly assess the situation as it now stands. We must guard against hope eclipsing reason, which is difficult to do when, as MS patients are fond of saying, time equals brain. With the omnipresent escort of progressing disability haunting us, we all want solutions, and we want them as quickly as possible.

Still, it's important to discern the realities of where the state of CCSVI research now stands. Many patients insist that the theory has been proven, and that a simple and minimally invasive procedure can halt or reverse the ravages of their illness. It's quite possible that they are correct about the procedure, but the fact is, as has been stated by Dr. Zamboni (click here) and some of the other leading CCSVI researchers and physicians themselves (click here and here), that research is desperately needed to prove or disprove the association between MS and CCSVI, that the procedures used to treat the venous abnormalities that have come to be called CCSVI need to be refined and perfected, and that new medical devices (stents) must be developed specifically for use within the CNS venous system.

Thus far, the only positive peer-reviewed research that has been published regarding the association between CCSVI and MS comes from Dr. Zamboni, and from the research team at the Buffalo Neuroimaging Analysis Center (BNAC), whose initial trial results involving 500 patients were released in April. All other reports are strictly anecdotal, and as such have little credence in the eyes of science. It's vital for completely independent researchers to confirm the initial groundbreaking work done by Dr. Zamboni, to firmly establish that CCSVI is significantly more prevalent in MS patients than in the general population, and, once confirmed, that CCSVI is a cause rather than an effect of the disease. Despite many patients’ belief otherwise, neither of these two propositions has yet been established in any scientifically valid manner. Only once CCSVI is determined to be a causative factor of MS will the MS societies fund studies on treatment.

In the meantime, privately funded studies looking at treatment options have already been proposed, and some should be getting underway sometime this summer.

The studies recently funded by the US and Canadian MS societies are targeted at precisely the two primary goals of proving the CCSVI/MS connection and showing that CCSVI is a cause rather than an effect of the disease. Much has been made of the fact that $2.4 million is hardly an overwhelming amount of money to be spent on CCSVI research, especially when placed in the context of the tens of millions of dollars being spent researching other aspects of MS, but at least it's a start. Without the groundswell of patient activism and advocacy, there most assuredly would have been no funding given to CCSVI research whatsoever, and I urge patients to continue to agitate for more, and more timely, research to be done.

The genie of patient activism is out of the bottle, and wielded wisely, can exert great influence on the powers that be. We must be careful, though, to guard against hysteria and extremism, to keep the CCSVI movement from being branded the lunatic fringe of the MS patient community. Discretion is often the better part of valor, and the movement would do well to heed Teddy Roosevelt's advice to speak softly and carry a big stick. That big stick is money, as the MS societies rely heavily on donations from the population at large (contrary to popular belief, only 5% of their contributions come from the pharmaceutical companies). I would expect that a smart and well-organized campaign that impacted the societies’ bottom line would quickly get their attention. Efforts can be made, too, to get CCSVI sympathetic members placed on the boards of the societies, as was recently tried unsuccessfully in Canada (click here). There will soon be CCSVI specific nonprofit organizations moving to the forefront, and support for these organizations should rank high on the list of those patients seeking to further the cause of CCSVI.

Switching to the question of diagnosis and treatment, I'm getting more and more concerned about people flying all over the world to get treatment that is quite possibly temporary (angioplasty) or carries with it unknown but very possibly real and troublesome risks (stents). Again, I completely understand the desperation of those willing to spend tens of thousands of dollars, and travel thousands of miles, to get treatment. I myself was lucky enough to get treatment locally, although my liberation procedure was unsuccessful (click here). But as the pool of treated patients grows, some obvious trends are emerging.

Even when initially successful, patients treated with balloon angioplasty are too often experiencing restenosis within weeks or months of the initial procedure. This means that they must either spend more time and money traveling across continents to be treated once again, or swallow their losses. Patients treated with stents are also experiencing problems with restenosis and clotting, and the very use of the currently available stents (which were designed primarily for use in arteries located within the chest cavity, vessels that differ dramatically in their anatomy from the veins associated with the CNS venous system), presents a host of potentially dire unknowns.

Dr. Zamboni has repeatedly stated that he's very wary of stents being used in the jugular or azygos veins, and when the doctor who treated me first presented my difficult case to Dr. Zamboni, Zamboni recommended traditional open neck surgery (as in, slicing and dicing) rather than stenting. Many patients have been stented for CCSVI successfully, but once those stents go in, they're in there for life, and nobody knows what affect the stresses of bending, stretching, and torque that the stents will experience in the neck will have as time passes. Stents specifically designed for use in the veins associated with the CNS are a must if CCSVI does indeed prove to be fact rather than merely theory.

Patients considering the liberation procedure must also keep in mind that not all patients treated see benefit, and some have even reported getting worse after treatment. We've all seen the miracle videos on the Internet, but people on whom the treatment had no or negative impact generally don't make videos for YouTube or show up on the various patient forums. Therefore, what we see and read on the Internet is extremely skewed towards the positive. Between patients who have contacted me through this blog and others that I know personally, I'm aware of quite a few people who have received absolutely no benefit from the procedure. Of course, given the heterogeneous nature of MS (the disease is very different in different patients), this shouldn't come as a surprise, but patients need to be keenly aware that the liberation procedure in its current form is not always the panacea that its most fervent advocates often assert it to be.

Another important consideration for those patients who do decide to pursue CCSVI treatment is the experience of the doctor doing their procedure. Most Interventional Radiologists (the specialists who do endovascular procedures) have far more experience treating arteries than veins. In fact, the CNS venous anatomy has been so little studied that no definition of "normal" has been agreed upon, and this anatomy can and does vary widely from patient to patient.

Furthermore, CCSVI is not limited to only one type of abnormality; a multitude of abnormal findings have been discovered in the jugular and azygos veins of MS patients. These abnormalities include vein narrowing, abnormal and dysfunctional valves, anomalous membranes, and even septums that divide the blood vessel in two. Many doctors just starting to do liberation procedures will have little experience dealing with this variety of abnormality. The physician who did my procedure, Dr. Salvatore Sclafani, has publicly stated that, despite 30 years experience doing catheter procedures, it wasn't until he had done the procedure on about 20 patients that he started to feel comfortable with the "art" of liberation, and that he was learning copious amounts with each patient he treated.

Undoubtedly, as more and more patients undergo the procedure, the methods and equipment used will be altered and refined, and procedures done a year from now will likely be much more sophisticated than those that have been done to this point. Although the idea of waiting for treatment is abhorrent to many patients, it may actually be in their best interests to allow doctors to gain the experience necessary to perform the liberation procedure effectively, safely, and with long-lasting results. We are in an age of discovery, and the book on CCSVI and the best ways to treat it has only started to be written.

In short, what we don't know still vastly outweighs what we do know about CCSVI and its role in MS. I personally believe that CCSVI will prove to be a major piece of the MS puzzle. I don't believe that it will be THE answer for all MS sufferers. The promise of CCSVI is tremendous, and in conjunction with advances being made in stem cell therapies, a new age in the understanding and treatment of MS could very well be dawning. But as tedious and frustrating as it might be, we must let the course of science wind its way towards definitive answers. Those who feel they cannot wait and choose to be pioneers in the treatment of CCSVI, would do well to remember the experiences of the pioneers who settled the American West. Some made it to California, struck gold, and became rich beyond their wildest dreams. Others, like the Donner Party (click here), became hopelessly stranded en route, and suffered disastrous consequences.

Due to the nature and speed of my disease progression, I decided to follow the trail blazed by the first and bravest pioneers, and underwent the liberation procedure, although I made it clear that I would only agree to balloon angioplasty, and would not consider the use of stents (my doctor was in agreement). I may revisit that decision as my disease marches onward. Each patient must decide for themselves their tolerance for risk, but hopefully, as the saga of CCSVI continues to unfold, those risks will be considerably diminished. At the very least, the issue of CCSVI has pushed researchers to look beyond the autoimmune theory, and that alone is a very good thing.

The Medical Industrial Complex: Sick People Required

Image by Getty Images via Daylife

Living life with a chronic illness such as Multiple Sclerosis gives one an inside view of the medical establishment, a view that healthy people rarely glimpse. In the blissful ignorance of good health, modern medicine appears to be bright and shiny, a miracle machine complete with magical elixirs, futuristic technology, and a sophisticated understanding of the maladies that strike human beings. Headlines and television news anchors shout about the latest medical breakthroughs, and a stream of television commercials assure us that there are pharmaceutical remedies for everything from cancer to osteoporosis to erectile dysfunction. Once sick and thrust into the belly of the beast, though, this illusion starts to fall away, and a different reality emerges.

Although there have been some incredible advances made in our efforts to heal sick humans over the last 50 years, there are still vast swathes of patient populations whose illnesses remain poorly understood, insufficiently and ineffectively treated, and ultimately incurable. Problematically, many of these patient populations generate billions and billions of dollars for the modern medical hierarchy, a situation that sets up a paradox within our profit driven medical establishment. Cure these patients, and vast sums of money and an elaborate infrastructure would simply evaporate; keep them perpetually reliant on hyper expensive medicines and medical procedures, and reap the fruits of an unending money machine.

Before I am accused of being a conspiracy nut, let me state outright that I do not believe that there is a cabal of evil, mustache twisting, demonic connivers assembled around a huge flaming conference table, snacking on deep-fried baby’s arms while plotting to keep cures and remedies hidden and out of reach from the desperately ill. If this were the case, the solution would be fairly straightforward; simply "out" the conspirators, and the walls would come tumbling down. Rather, the problem has become incorporated into the system itself, insidious and inherent, the logical outcome of the evolution of a medical industrial establishment that has come to view sick people as consumers and horrendous illnesses as opportunities for tremendous financial gain. This system does not require people with malicious intent to keep it functioning; it only needs decent people doing their appointed jobs to the best of their abilities to keep the gears turning.

As previously stated, the past 40 or 50 years have seen some incredible medical advances, most of them in the fields of surgery and in the treatment of traumatic injuries and infectious illnesses. Organ transplants, less invasive surgical techniques, and an ever increasing understanding of human physiology have combined to put a shine on many facets of modern medicine. A patient's chances of surviving a heart attack, or avoiding having one in the first place, are much better now than in 1950. Knee injuries that in decades past would have necessitated complex and sometimes crippling surgery can now be done using arthroscopic techniques requiring only tiny incisions, with recovery times measured in a few short weeks rather than many grueling months.

The treatment of some of our most dreadful illnesses, though, have not seen such advances. Ask the average person about the chances of surviving cancer today vs. 1950, and I would expect that most would tell you that your odds of beating the disease are much better now than they were 60 years ago, a belief driven largely by the almost relentless marketing done on behalf of the medical profession. The New York Times, though, reports that "the death rate for cancer, adjusted for the size and age of the population, dropped only 5 percent from 1950 to 2005." (Click here for article). Headlines blaring about the latest advance in cancer drugs rarely mention that the studies cited often declare a cancer drug "effective" even if it increases the lifespan of the patients taking it by only a handful of weeks. The fight against some forms of cancer has indeed benefited from modern medical advances, but for many cancers, little real headway has been made.

Since the vaccine for polio was found in the mid-1950s, very few if any diseases have actually been eradicated. Instead, the trend is towards turning diseases such as diabetes, AIDS, some cancers, and multiple sclerosis into treatable chronic illnesses, their patients heavily reliant on fantastically expensive medications and interventions. The reason for this lies largely in the fact that over 70% of our medical research is carried out by pharmaceutical companies, whose primary mandate is to generate financial profit.

The job of a publicly traded pharmaceutical company CEO is to constantly drive up the price of his company's stock, not to facilitate the creation of drugs that would be of the most benefit to the patients taking them. This isn't a question of morality, but of economics. The drug companies, and those who manage them, are merely doing what every other business endeavors to do in our free-market capitalist system, to constantly increase profit. I'm all for free-market capitalism; in recorded history there has been no better economic driver and creator of wealth. Unfortunately, when applied to healthcare, in many cases good economics has led to very bad medicine. The corroding influence of big money, in addition to an environment of lax regulation, has led to some shocking abuses of the system, such as the marketing of drugs that are known to be dangerous (click here for info), and the suppression of studies whose results are unfavorable to the drug being tested (click here for info).

Over the past three decades, pharmaceutical companies have discovered that the best way to increase profit is to market "blockbuster" drugs that patients must stay on for the rest of their lives. In the case of multiple sclerosis, this has led almost all research to concentrate on compounds that alter or suppress the human immune system, based on the "autoimmune model" of the disease, which states that MS is the result of an immune system gone awry. In reality, it's becoming more and more clear that the aberrant immune response seen in MS patients is more a symptom than a cause of the disease. Some unknown agent is driving the immune system to attack the central nervous system, the latest and hottest theory being that the vascular abnormalities collectively known as CCSVI (click here for info) might be the cause.

Since the mission of pharmaceutical companies is to generate the most bang for their research bucks, they direct their research dollars to projects that have the best possibility of leading to substantial profit. This, in turn, influences the behavior of even the most well-meaning medical researchers, who, just like everybody else, need to feed their families and pay their bills, and who naturally seek to advance their careers. Thus, they are drawn to investigations that will most likely win hotly contested research dollars. That funding, the vast majority of which comes from the big pharmaceutical companies, goes almost exclusively into researching novel compounds that can be patented and remain the sole property of the company that discovers them for many profitable years.

This same dynamic inherently underfunds research seeking to eradicate diseases that have each, in effect, become multibillion dollar a year industries. This is not because of evil or malicious intent, but instead is the result of the economic engine that drives what can be called the "medical industrial complex", the misguided marriage between profit-seeking corporations and the healthcare industry, which requires a perpetual supply of sick people to keep the money flowing. This need for patients is so intense that it can sometimes lead previously untreated and relatively benign conditions to be deemed diseases that require pharmaceutical intervention, as in the case of osteopenia (click here for details).

This same drive also leaves many potentially effective but unprofitable remedies untested and relatively ignored. Drugs such as Low Dose Naltrexone (LDN) and the effects of diet and natural remedies have barely been studied for their impact on MS, simply because there is no profit to be made from them. Recently, a cheap blood pressure medication, Lisinopril, has been shown to have some promise as an MS drug. This discovery wasn't made by any run-of-the-mill research scientist, but by Dr. Jim Steinman, one of the inventors of Tysabri, a very expensive and controversial MS medication that is very effective but also carries with it the possibilities of very serious side effects. Dr. Steinman would like to see a full scale human study of the effects of Lisinopril, but says that "Lisinopril is as inexpensive as any prescription drug at this time, so pharmaceutical companies won't see any profits from financing a study" (click here for article). Thus, the drug remains unstudied in its effectiveness against MS, for now and probably forever.

It's hard to see a solution to this disheartening status quo, other than a significant increase in the government funding of medical research. Unfortunately, the trends are heading in the opposite direction, with more and more funding coming from the private sector, as public dollars become scarcer and scarcer in this age of soaring deficits and cries for smaller government.

As a patient suffering from MS, the situation is incredibly frustrating, as it's clear to me that much of the research now being done on the disease is not conducted with patient benefit as its primary underlying goal, but rather with the profit potential and market share that each patient represents as the target. The recent CCSVI controversy has brought this situation into focus for thousands of MS patients, because if relatively simple vascular surgery can indeed treat MS effectively, the multibillion dollar a year treasure chest that is MS will be wrested from the grasp of the pharmaceutical companies, whose financial influence within the medical and political sectors cannot be overstated. The medical industrial complex is a self-perpetuating entity that will not easily be shut down, the sheer force of its financial weight creating an almost irresistible momentum.

I'll let my final words on the subject be these: As a just and honorable society, please, view me first as a patient, not as a consumer. Human suffering should never be treated as a commodity, regardless of the considerable economic incentives to do so.