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?