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!

Can Anti-HIV Drugs Stop MS?

Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands. (Photo credit: Wikipedia)

(Readers who receive these posts via email are advised that this essay contains a video, which cannot be viewed in the email version. Please go to the Wheelchair Kamikaze website (click here) to view the video…)

I imagine the above headline might have furrowed a few eyebrows and crinkled some foreheads when first viewed by readers. HIV (the virus that causes AIDS) has nothing to do with MS, does it? Has Marc finally lost his last marble? Don’t MS patients have enough to worry about without having to contemplate AIDS?

Yes, MS patients certainly do have enough to worry about, and no, the virus that causes AIDS has nothing to do with multiple sclerosis. HIV, though, is a retrovirus, and, strange as it might sound, there is increasing evidence that ancient retroviruses that have become incorporated into the human genome through millions of years of evolution may play a key role in the MS disease process. This might seem like something out of a science fiction novel, but this discovery of prehistoric viral material in human DNA has the potential to completely change the way we understand and treat MS and other diseases (including cancer), and could potentially lead to – dare I say it – a cure.

There are currently two clinical trials underway attempting to shut down these ancient retroviruses in MS patients, and one of them uses a currently available anti-HIV drug. More on these trials a bit later, but first a little background, starting with a quick overview of virology. I know the mere prospect of “a quick overview of virology” is apt to make eyes glaze over throughout the Internet, but please bear with me, I’ll try to keep it as painless as possible.

We’re all familiar with viruses, the little buggers that cause influenza, the common cold, and a many other diseases. Of course, bacteria also cause diseases, but viruses and bacteria, though both infectious agents, are very different beasties. Bacteria are living organisms, and when someone suffers a bacterial infection they can usually be treated with antibiotics, drugs which kill the guilty bacteria and thereby cure the patient. Antibiotics have no effect on viruses, though, because viruses aren’t alive, and therefore can’t be killed. Viruses are kind of like the zombies of the pathogen world, undead infectious agents that exist only to infect living things. The fact that viruses are “undead” is what makes viral diseases so hard to treat, and why we still don’t have a cure for the common cold.

Unlike living bacteria, which can reproduce all on their own, undead viruses replicate by hijacking their victims’ cells and then using the resources within those cells to reproduce themselves. Most viruses kill the cells they invade by replicating to the point where the infected cells burst, releasing the reproduced viruses and thus spreading viral infection throughout the body. Another type of virus, though, called a retrovirus, actually inserts itself into the host cell’s DNA, and in effect become part of the organism they have infected, commandeering the host’s genetic material and cellular mechanisms to replicate themselves without destroying the cells they have invaded. This makes retroviral diseases (such as AIDS) extremely hard to treat, and coming up with ways to neutralize retroviruses has presented medical science with one of its most daunting challenges.

Now, here comes the really strange part. When the Human Genome Project (click here) completed the incredibly complex task of mapping all of the genes contained in human DNA, it was discovered that 8% of our genetic material is comprised of the remnants of ancient retroviruses, many of which inserted themselves into our genetic material tens of millions of years ago during the evolutionary process, before humans were even human. These retroviruses were at one time in the distant past infectious, but have long since been rendered dormant, and it was initially thought that they were nothing more than “junk DNA”, left over genetic material that plays no role whatsoever in the development or functioning of a human being. These ancient retroviruses that are now part of the human genome were named Human Endogenous Retroviruses, or HERVs. They are a part of all of us, genetic remnants of our evolutionary history.

Recent research into HERVs has provided tantalizing clues that rather than always remaining dormant, in certain circumstances these ancient viruses can be activated and may play a key role in many diseases, including multiple sclerosis, many autoimmune diseases, some cancers, and even schizophrenia (click here, here, here and here). The mechanism by which HERVs are activated are not fully understood, but the prevailing thought is that the presence of other viruses and environmental agents, such as Epstein-Barr virus (click here), the human herpesviruses (click here), and other environmental triggers, or a combination of these elements, may “wake” these bits of ancient viruses that are part of our DNA. Once activated, this ancient retroviral DNA can cause our own cells to secrete proteins and antigens that may identify the host cell as a hostile invader, or otherwise initiate critical disease processes.

Within the last five years or so, it’s been established that virtually every MS patient is infected with Epstein-Barr virus (click here), which is best known for causing mononucleosis/glandular fever. I know, many of you are saying, “but I never had mononucleosis or glandular fever, so I don’t have EBV!” The fact is that in the majority of cases infection with Epstein-Barr virus does not result in Mono, but rather can present as a bad cold or flu, or can even be completely asymptomatic. Over 90% of the general population is infected with EBV, but, remarkably, it appears that 100% of MS patients carry the bug. MS researchers have long puzzled over the role EBV might play in the MS disease process, since EBV infection alone certainly can’t be the sole cause of MS, otherwise far more people would have multiple sclerosis. The link between EBV and HERVs could finally clear up this mystery, for if a long-term EBV infection can turn on ancient retroviruses embedded in the DNA of genetically susceptible people, the connection between EBV and MS might finally be understood (click here).

Though the connection between HERVs and MS has yet to be proven, more and more evidence appears to be pointing in that direction (click here), and the hypothesis does pull together some of the “wildcard” factors that have confounded MS researchers for decades. Among these factors are indicators that there is an infectious component to MS, such as the existence of “MS clusters”, geographic locations where MS appears to run rampant among the local population (click here), and migratory studies which show that migration from areas of high MS to areas of low MS before the age of 15 decreases the risk of getting multiple sclerosis, with the reverse being true as well (click here). Through the years many possible infectious candidates have been proposed, to no avail, but if the HERVs theory is correct, it’s a combination of infectious agents, including some hiding in a patient’s own DNA, that may be responsible.

Both EBV (which is itself a human herpesvirus) and retroviruses have proven to be extremely difficult to eradicate, as can be illustrated by the fight against HIV. HIV is a retrovirus, and although medical science has made great strides in developing drugs that keep HIV infection under control (deaths from AIDS have plummeted in the last decade), there is still no way to completely eradicate the virus from the body of an infected person. One anti-HIV drug, Raltegravir (brand name Isentress) (click here) has proven to be quite effective in combating HIV, though, and also shows promise as an anti-EBV weapon.

A clinical trial now underway at Queen Mary University in London, England, called be INSPIRE trial (click here), is attempting to use Raltegravir to treat MS patients. Researchers hope that the drug will deactivate any activated retroviral material in the DNA of MS patients, while perhaps also combating EBV, and thus stop multiple sclerosis in its tracks. Another group of researchers in Switzerland are trying to accomplish the same outcome using an experimental drug that targets a protein on a specific HERV that is thought to be directly connected with MS, which has been dubbed the Multiple Sclerosis Associated Retrovirus, or MSRV (click here). This is a small, 10 person Phase 2 trial whose primary goal is to establish the safety of the experimental drug being tested. Results from the INSPIRE trial, which is just getting underway, are not expected until August, 2014, and the results from the Swiss trial are expected in July of this year.

It’s impossible to overstate the potential that this research has to completely reshape the multiple sclerosis landscape, with vast implications impacting the quest to wipe out many other horrendous diseases as well. If indeed prehistoric viruses embedded within our own DNA are at work driving the MS disease process, shutting down these viruses could amount to a cure. Yes, a cure for multiple sclerosis! Though it may be hard to believe, there is precious little work being done elsewhere to uncover the roots of MS, as so much research time and money is devoted towards finding newer and more effective (and more profitable) ways to suppress the aberrant immune response that is seen in the disease, a response that is in fact a symptom of some as yet unknown underlying cause. All of the current crop of MS drugs, and the vast majority of those in the experimental pipeline, either modulate or suppress the immune system, a mechanism of action which can sometimes dramatically improve the quality of life of RRMS patients, but will never do anything to cure multiple sclerosis. The research going on in London and Switzerland at last holds out hope for a cure, and represent a radical rethinking of the cause of many of the diseases that plague mankind.

My intuition and instincts tell me that these research scientists are onto something, and it’s something potentially huge. It’s long been known that genetics play a role in MS, and it has also long been suspected that infectious agents are at work. The idea that Human Endogenous Retroviruses, bits of viruses that are in a very real way a part of us, encoded into our DNA, could play a key role in the MS disease process ties together both of these observations, as well as several others. The evidence to support this idea is mounting, and to me this hypothesis feels right in a way that no other MS related theory I’ve come across has before. Of course, you can (and probably should) take my “gut feelings” with a grain of salt, but I find myself brimming with enthusiasm that the science of treating MS is finally moving in the right direction. Of course, as I’ve often cautioned before, it’s vital not to let hope eclipse reason, and this research might well lead to nothing. But, somehow, I just don’t think that it will…

Here’s a terrific video presentation by one of the lead researchers involved in the INSPIRE trial, which does a great job of explaining the research and the ideas behind it in a very accessible, easy to understand manner. I urge all readers to watch this video, as the information it contains has tremendous potential…