Friday, September 20, 2013
Stem Cell Treatments for Multiple Sclerosis
As all patients with MS are aware, the currently available treatments do nothing to cure the disease or repair the damage that it does. At their best, today’s crop of disease modifying drugs (DMDs) quiet the disease, thereby improving the quality of life for many of the patients taking them, especially those suffering from relapsing remitting multiple sclerosis. However, many of these drugs carry with them risky side effect profiles, and though the newest compounds represent advances over their predecessors, patients are crying out for revolution, not evolution.
Stem cells could represent the revolution patients so fervently desire. Because of their ability to transform into almost any type of cell in the human body, stem cells may hold the key to achieving one of the holy grails of modern medicine, the regeneration and repair of damaged tissues. For MS patients, this could potentially mean the reversal of disability, and with it the long dreamt of disposal of wheelchairs, walkers, and canes. We are still a long way from that lofty goal, however, but the first few steps along the path to that salvation are currently being taken.
Though stem cell research is advancing in laboratories worldwide, the science of using stem cells to treat diseases in humans is still in its infancy. Because multiple sclerosis is a neurodegenerative disease, and its most prominent feature is the damage the disease does to the central nervous system, it is hoped that stem cells may hold the key to reversing the carnage wrought by the disease by facilitating the repair of damaged nerve cells. Furthermore, research has provided hints that stem cells may modulate the abnormal immune response seen in MS patients, and some researchers are even using stem cells to completely reboot the human immune system, a process that in some cases appears to stop the disease dead in its tracks.
It’s important to understand that there are two very different approaches to using stem cells in the treatment of multiple sclerosis. One approach hopes to use the cells to repair damaged nervous systems; the other uses stem cells to provide the patient with a brand-new immune system, one that theoretically will not turn against a patient’s own body. The latter approach is known as hematopoietic stem cell transplant, or HSCT, and has been used on patients in trial settings for almost two decades.
HSCT involves ablating (destroying) a patient’s existing immune system through the use of powerful chemotherapy drugs, and then intravenously infusing a patient’s own stem cells back into their body, a process depicted in the below diagram:
Once infused back into a patient’s body, the stem cells go about reconstituting their immune cells, effectively providing them with a brand-new immune system that in theory shouldn’t go to war against the patient’s own brain and spinal cord. In practice, this type of therapy has proven to be quite effective, particularly among patients with aggressive relapsing remitting disease who display a high amount of inflammation in their central nervous systems, as are evidenced by enhancing lesions seen on MRI imaging.
As you might imagine, using powerful chemotherapy drugs to destroy a patient’s immune system is not without its dangers, and early attempts at this therapy had mortality rates as high as 10%. As researchers perfected their methodology and began using less dangerous chemotherapy agents, though, the risks associated with HSCT dropped dramatically. Today, most patients undergoing HSCT are subjected to chemotherapy and immunosuppressive agents that do not completely destroy their bone marrow, and the safety profile of the procedure has improved impressively. The results achieved by this HSCT can be dramatic. In one study (click here) that looked at the long-term outcomes of HSCT, after 11 years 44% of patients who had started out with aggressive relapsing remitting disease were free from disability progression. By comparison, only 10% of those who did not display signs of active inflammation before HSCT remained stable.
One of the primary proponents of HSCT therapy for MS patients, Dr. Richard Burt of Northwestern University, stresses that the proper selection of patients is the key to the success of the treatment. In fact, the title of the paper he recently published (click here) includes the phrase “if no inflammation, no response”. “It’s the only therapy to date that has been shown to reverse neurologic deficits,” said Dr. Burt, “But you have to get the right group of patients.” In a study published by Dr. Burt in 2009, 17 out of 21 relapsing remitting patients improved after HSCT, and after three years all patients were free from progression (click here). Dr. Burt is currently heading up the HALT-MS trial for HSCT (click here). There are several centers around the world offering HSCT therapy, and there is a Worldwide HSCT Facebook group (click here) that contains information on all of the legitimate HSCT facilities worldwide. The group is populated by many folks who have undergone HSCT therapy. Be aware that it’s a private group, and you must request membership before being given access to all of the available information.
While HSCT holds much promise for putting the brakes on very aggressive relapsing remitting multiple sclerosis, it unfortunately has little to offer those with progressive disease, and does nothing to directly repair the damage done to the central nervous system by MS. Fortunately, another form of stem cell therapy proposes to do just that. Researchers in two centers in the US have received FDA approval to use bone marrow derived mesenchymal stem cells (MSCs) to repair nervous system damage, thereby possibly reversing the effects of the disease. There are additional trials using MSCs to treat MS underway internationally. Mesenchymal stem cells have the ability to transform (differentiate) into many different cell types, and could prove to be the building blocks necessary for repairing damage to the central nervous system as well as other organs and tissues. Experiments using MSCs to treat animal models of MS have been very encouraging (click here), demonstrating the cells’ abilities to modulate the immune system and spur the repair of damaged nervous system tissues. It remains to be seen whether the same effects can be achieved when using the cells to treat human beings.
The two FDA approved studies both use MSCs harvested from a patient’s own bone marrow, but employ them in very different ways. One study, currently underway at the Cleveland Clinic (click here), infuses mesenchymal stem cells intravenously into the patient, in the expectation that the cells will modulate the immune system and also initiate the regeneration of damaged tissues in the central nervous system. This study, which will eventually use MSCs to treat 24 patients, is proceeding slowly, but as the above linked to article details, one of the first patients treated is already reporting encouraging results.
The second FDA approved trial, to be conducted by the Tisch MS Research Center of New York (which just so happens to be my MS clinic), will use mesenchymal stem cells that have been transformed through a proprietary laboratory process into neural progenitor (NP) cells, injected directly into the spinal fluid (intrathecally)) of the patient (click here). Neural progenitor cells are a specialized type of stem cell specific to the nervous system that have the ability to transform into the various types of tissues damaged and destroyed by the MS disease process. Researchers at the Tisch Center have developed a way to get mesenchymal stem cells to differentiate into neural progenitor cells, and hope that by injecting these cells directly into the spinal fluid the NP cells will directly target the regenerative mechanisms of the central nervous system (click here). The stem cells themselves may act to repair damaged tissues, but they’ve also been shown to have the ability to recruit existing stem cells within the brain and spinal cord to jumpstart the body’s own repair mechanisms.
It’s important to remember that both of these studies represent a very different approach to stem cell therapy for MS than HSCT. The primary goal of HSCT is to reboot a patient’s immune system; HSCT does nothing to directly address the damage that has already been caused by the disease, but rather seeks to disrupt the disease process. Taking a different approach, the trials being conducted at the Cleveland Clinic and the Tisch MS Center seek to effect repairs on the damaged brains and spinal cords of MS patients, albeit through two different methodologies. HSCT and the reparative therapies being tested in the FDA trials have little in common other than the fact that they both use stem cells in an attempt to treat MS.
I’m sure that many patients reading this are aware that there are clinics in Central America, Asia, and Europe offering regenerative stem cell therapy to patients at hefty price tags. Some of these clinics aggressively market their services, and typically charge $20,000-$40,000 for a single round of stem cell therapy. Various Facebook pages, blogs, websites and posts on MS Internet forums extol the virtues of the treatments these clinics provide, often offering glowing testimonials from patients they have purportedly treated. Although I don’t want to disparage any patient relating their genuine experiences with these clinics, I’ve known several MSers that have traveled to a variety of these clinics and undergone stem cell treatments, and unfortunately none of them have experienced anything in the way of significant or lasting benefit.
I would caution anybody considering treatment in Panama, Costa Rica, Germany, India, or any of the other clinics offering stem cell therapy without any published scientific proof of the effectiveness of their treatments to think long and hard before committing substantial amounts of money for a therapy that, according to the experiences of people that I actually know, has very little chance of working. The two legitimate trials I outlined above both involve multiple treatments given over an extended period of time, using cells that have undergone lengthy (months long) processes of multiplication and/or differentiation in the laboratory before being transplanted back into the patient. Such regimens are not followed by the “pay to play” clinics; instead, they generally infuse stem cells back into the patient soon after they are harvested, and offer extremely limited, if any, follow-up care.
Additionally, some of these clinics don’t use a patient’s own stem cells for treatment, but rather umbilical cord cells, on which far less research has been done. The use of stem cells not derived from the patient themselves opens up all kinds of questions regarding safety and efficacy, as the cells are genetically different from the tissues they are meant to repair. If any of these clinics regularly achieved anything close to the number of successful outcomes that they claim, they would surely publish their results in legitimate scientific journals and reap the personal and professional accolades that would follow. Can you say Nobel Prize? Instead, they publish marketing materials and partner with travel agencies. Reason enough for skepticism. In short, let the buyer beware.
Stem cell therapy holds tremendous potential for the treatment of multiple sclerosis, and provides much reason for hope. The efficacy of HSCT for treating very aggressive relapsing remitting multiple sclerosis is well documented, and the safety of this treatment regimen has increased dramatically as practitioners have perfected the process. Regenerative stem cell therapy, of the type currently being trialed at the Cleveland Clinic and Tisch MS Research Center of New York, is still in its infancy, but is bursting with promise, possibly holding the key to repairing the damage done by multiple sclerosis and restoring function robbed by the disease. As with all new therapies, though, it is vitally important to not let hope eclipse reason, or let hype cloud judgment. We are at the dawn of a new age, and I fully believe that the use of stem cells will revolutionize the practice of medicine. Research into the use of stem cells to treat MS is quickly picking up steam, and in combination with other emerging therapies, rays of hope are finally being shone upon the disease and those afflicted with it. It’s about time, don’t you think?
Sunday, September 1, 2013
A Half-Century on Planet Earth
Naturally, dealing with a progressively disabling disease for the last 10 years has impacted the way I think about age and aging. I read somewhere that inside every 50-year-old there is an 18-year-old screaming "what the hell happened?", and though I’m sure that sentiment is true for just about everybody, it’s especially resonant for those dealing with something as completely unexpected (and dreaded) as a debilitating chronic illness. Experiencing my 50th birthday while sitting in a wheelchair is definitely not something I ever pictured back when I was dreaming of rock 'n roll glory and earning a degree in film. Polishing my prolific collection of well-earned Oscars or platinum records, yes; firmly planted half paralyzed in a mechanical monster, certainly not. Better, though, to be planted in a wheelchair than planted in the ground. As Dr. Einstein said, it’s all relative.
Way back in the late summer of 1963, I was born three weeks prematurely via cesarean section, a circumstance necessitated by the type I diabetes that struck my mom while she pregnant with me. Unlike the majority of gestational diabetes cases, my mother’s never resolved, and she’s been injecting herself with insulin multiple times a day ever since. When I was surgically snatched from the womb it was discovered that my lungs were completely filled with fluid, a situation quite dire. Just a few weeks earlier, President Kennedy’s wife Jackie had given birth to a baby boy suffering from the exact same condition. Little Patrick Kennedy died two days later.
My parents were acutely aware of the tragic circumstances of the Kennedy baby’s death when the doctors informed them of my condition, stating that I had only a 50-50 chance of surviving my first 48 hours. I was whisked away and placed in an incubator before my mom even had a chance to hold me. My dad, on leave from a training stint in the National Guard, was ordered to return to his base that day, despite not knowing whether or not his firstborn would make it through the night. A grim circumstance for sure, but I came out on top of my very first scrap, beating back an early demise by fighting for my first breaths. Three days later I was out of the incubator and finally placed in my mom’s warm embrace. Such is the randomness of the universe; a President’s son dies, and an anonymous little Jewish kid in the Bronx survives. It’s nice to know that I have a history of beating the odds, and leave it to me to make such a dramatic entrance onto the stage of this great big theater of the absurd.
In a sense, getting diagnosed with MS led me to a sort of rebirth, as the course of my life was altered so dramatically as to cleave it in two. There was part one, which spanned the time from my birth until my disease put the brakes on the running narrative of my existence, around the time I was forced to “retire” and go on long-term disability. Thus started part two, a reality that grows increasingly divorced from that previous incarnation, so much so that I can now look back on part one as an entity in and of itself, a story with a beginning, middle, and end. As such, from my new and somewhat unfortunate vantage point – a view filled with unexpected perspective – I can examine my old life like a biologist probing a particularly enigmatic specimen, teasing it apart in an attempt to discover the mysteries held within. I can trace the complicated web of experiences, circumstances, decisions, and happenstance that coalesced to form the story of my life, the subtle twists of mind and fate that led me to travel one path while bypassing an infinite number of others. If I had made a different decision here or there, if I had perhaps not lingered for one more drink or to furtively admire a pretty girl, or had not allowed fears of failure and success to exert their undue influence, might the path then taken have led to an entirely different destination, or did all roads invariably lead to Rome? Was I at the helm of the ship of destiny, or at the mercy of the cosmic winds?
In steadily untangling the jumbled knot of fate and self-determination which comprised that now extinct existence, I can in retrospect readily recognize the all too many wasted moments pregnant with possibility, can identify errors great and small made along the way, and take satisfaction in the many things that went right. The one thing I cannot do is change any of it; I can roll it around and dissect it ad infinitum, but the circumstances and outcomes of my old life will always remain frozen in time, like 200 million-year-old insects visible in pieces of amber, fascinating to gaze at but impossible to resurrect.
And, now, what to make of this new incarnation, this part two, so unwanted but also filled with its own peculiar brand of wonder and surprise. Certainly, many aspects of it are excruciating: the disease itself, the gradual loss of physical function, the sheer helplessness in the face of this progressive beast that gnaws away at me, the frustrations with a medical establishment that is shockingly ill-equipped to slay it. Despite these negatives, in a bizarre twist of fate the disease has bestowed upon me a freedom few adults ever experience. I am no longer bound by the shackles of work (I guess you can tell how much I loved working), and because of this I've been granted the gift of time, most of my days spent in a manner of my own choosing. Certainly, the disease imposes limits on my menu of choices, but even within those boundaries, whose borders are ever contracting, I’ve been able to pursue long sublimated passions, passions that had fallen victim to the realities of the workaday world. Writing, photography, a fascination with science and research, a need to communicate, all of which have gratefully come together on these virtual pages, reflections of parts of me that I had almost forgotten existed.
To think that people actually read these words and appreciate my photographs, well, it just about defies belief. This part two, this second act brought about by the realization of some of my worst fears, has graced me with the privilege of making friends in faraway places, of expressing thoughts and emotions that I’m told bring comfort to many and thus bring comfort to me, of hopefully helping to empower and offer distraction to my fellow wanderers along this road that none of us would’ve ever chosen to follow . Can this curse then, at times, be seen as something other than a vulgarity? Kipling wrote that triumph and disaster are both impostors, two sides of the same coin, and a keener observation was never made.
I look back on my 50 years and acknowledge my regrets while also celebrating my achievements. I revel in the rich tapestry of experiences and episodes I was lucky enough to be part of that will always make me smile. I’ve flown in the Goodyear blimp, come face-to-face with an apparently not very hungry 10 foot bull shark while snorkeling, won $14,000 in a state lottery, hit a hole-in-one in golf. Far more important than any of those moments, though, are the friends that I’ve made along the way, a precious few that have been part of my life for decades, others that have come and gone, but all of them more dear than any fleeting moment of experience ever could be. I thank the heavens for a wife who is the sweetest soul I’ve ever known. I mourn the friends and family that have passed, from 18-year-old Kimberly, her life cut obscenely short so many years ago, to David, the smartest man I’ve ever known, to The Greek from Detroit, my comrade in arms, to my grandmother, who even at 97 years old could make me laugh like no other. I miss them all, and will for all my days.
My 50th birthday provoked in me more introspection then any of the other milestone birthdays I’ve passed along the way, none of which ever really fazed me. Being afflicted with an unrelenting illness makes pondering the future a daunting proposition, and yet within me still resides a bubbling fount of hope. One of my oldest friends once described me as the most optimistic pessimist he’d ever known, and I think he got it right. Though I can often be a glass half empty guy, I’ve always expected to find that other half glass somewhere just over the horizon.
The disease that sliced my life in two has taught me that no matter how astute you fancy yourself, you never know what’s just around the next bend, and whatever comes into view is neither good nor bad but what you make it. As any good poker player knows, the key to winning big is not the hand you’re dealt but how it's played. There is infinite wonder in the world and in the people who occupy it. In one hundred years, the world will still be here, but all of us will be gone. No sense taking yourself too seriously, then, because we are, in the end, all just ephemera. Rejoice in that notion; nothing about us is ever written in stone, except our name on a marker that we’ll never see. Even after 50 years I’m still a work in progress, and in that sense, perhaps there's still a little part of me left in that incubator I was placed in all those years ago.
Here's a great old song that expresses one of the most important keys to contentment that the past 50 years have taught me: Be thankful for what you've got… I love the photos in the video, too, which remind me of the good old/bad old New York City that I grew up in. For those who may not be aware, the subways in NYC haven't been covered in graffiti for about 25 years.
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