Tisch Center MS Stem Cell Trial: Interview with Dr. Saud Sadiq, Director and Lead Research Scientist (Part Two)

Dr. Sadiq and research staff at the Tisch Center

The Tisch MS Research Center of New York (click here) will soon begin its first-ever FDA approved Phase 2 regenerative stem cell study for multiple sclerosis. Last week, I published the first part of my interview with Dr. Saud Sadiq, the Director and Lead Research Scientist of The Center, which discussed  the Phase 1 study and its results (click here). As promised, here is the second part of our discussion, which focuses on the upcoming Phase 2 study, the Tisch Center's new stem cell laboratories, how stem cells might help repair damaged nervous system tissues, and some of the other multiple sclerosis research projects being conducted by Tisch Center researchers and scientists.
This interview has been lightly edited for readability, and I’ve added some “WK Notes,” which attempt to translate overly complicated medical jargon into plain English.

WK: The Tisch center is now preparing to embark on Phase 2 of your MS stem cell trial. When do you expect this next phase of the study to get started?

Dr. Sadiq: After the  Phase 1 study ended, we made a commitment at The Tisch Center that we needed to make our stem cell laboratories absolutely state-of-the-art. We’ve invested heavily in building a new stem cell lab, which is being completed now. Everything’s automated, it’s a next generation stem cell facility that will be functional and certified in about a month and a half. Then we will be prepared to start the Phase 2 study. We do still need some additional funding for Phase 2. We are applying to the National Multiple Sclerosis Society for a grant. Though they didn’t support Phase 1, given the impressive results of that trial we are hopeful that they will support us as we go forward. We also expect private contributions to help fund Phase 2, as these have always been the lifeblood of the foundation.

WK: How many patients will be involved in the Phase 2 study?

Dr. Sadiq: There will be 50 patients involved. It will be a double-blinded crossover study specifically designed to establish the effectiveness of the neural progenitor stem cells we've developed in our laboratories. So it has an entirely different aim than the Phase 1 sstudy, which was intended primarily to determine the safety and tolerability of our stem cell procedures. We are going to give Phase 2 study participants six treatments, one every two months. Therefore there will be more treatments given in greater frequency than in the Phase 1 study.

WK: So, with 50 patients, 25 will be getting actual stem cells, and 25 will be getting placebo treatments?

Dr. Sadiq: Yes, in the first year 25 subjects will get treatment and 25 will get placebo, and in the second year the ones who got placebo will get treatment and vice versa.

WK: What will the patient population look like for this Phase 2 trial?

Dr. Sadiq: The patients for this trial will have to meet much tighter inclusion criteria then the patients in Phase 1. They all must be diagnosed with SPMS or PPMS. They have to be ambulatory, so they’ll all have EDSS scores between 3 and 6.5. The FDA is requiring that we have an equal distribution of the EDSS scores. So there will be equal numbers of patients distributed between all the points along the EDSS scale. The other limitation is that all patients will need to have had the disease for 15 years or less.

WK: Will the study participants continue with their disease modifying drugs?

Dr. Sadiq: Yes, but they can’t have switched medications within six months from the start of the trial.

WK: Once they are in the trial they’ll have to remain on the same DMD for the duration of the study?

Dr. Sadiq: Yes.

WK: What will be the total duration of this trial?

Dr. Sadiq: There will be two years of study and placebo, and one year of follow-up. So a total of three years.

WK: Just to be clear, in the third year none of the patients will be receiving stem cells?

Dr. Sadiq: That’s correct, in the third year there will be no stem cells and no placebos. After the second year, all patients will have received six treatments. The patients who received stem cells in the first year will have placebo in the second year, and the patients who received placebo in the first year will receive stem cells in the second. The third year will be for observation of all patients.

WK: For all the folks out there with RRMS, if the Phase 2 trial proves successful then the stem cell protocol developed at Tisch could be applied to them as well, correct?

Dr. Sadiq: For patients with relapsing-remitting disease who experience a relapse that results in damage from which they don’t recover, stem cells could be introduced in an attempt to repair that damage. That would be the dream scenario, and it could render disability resulting from MS a thing of the past. But at this point were getting ahead of ourselves…

WK: As we move forward into a world in which stem cell treatments for MS become a standard of care, would you anticipate that patients will need continued and repeated stem cell treatments to maintain or advance whatever benefits they realize until a cure is finally found for multiple sclerosis?

Dr. Sadiq: Yes, that’s likely. I think the Phase 2 trial will really go a long way towards answering that question. It will be important to ascertain what happens to patients in the years after they receive their stem cells. Do they maintain their benefits, do they return to baseline, or do they fall somewhere in the middle? These will be significant findings. The design of this crossover trial will allow us to figure that out. My feeling going in is that patients will need stem cell treatments over the long-term, maybe not six a year after the initial treatment., but perhaps less frequently to maintain whatever improvement is seen.

WK: The neural progenitor cells developed by the Tisch Center – or any regenerative stem cells, for that matter – don’t directly address the disease process, correct? If so, does the disease remain active despite the use of these stem cells?

Dr. Sadiq: Yes, that’s right, the cells are not a cure for the disease. They hopefully secrete trophic factors that would stimulate the body’s own progenitor cells to activate and induce repair at sites of injury. (WK Note: trophic factors are elements which cause the body to maintain or start some action, in this case repairing damaged nerve cells and possibly affording some protection against attack from immune cells.)

WK: So, the stem cells may not necessarily repair injury all by themselves, but they may jumpstart natural repair mechanisms within the bodies of the patients in which they are implanted?

Dr. Sadiq: I think that’s the most likely mechanism. Whether they play some direct role is something we have to figure out, but I think it’s more likely that they’ll turn on a patient’s own progenitors and also create a trophic environment that acts as a shield from the immune system and allows the body to make repairs.

WK: I know that stem cells aren't the only focus of the Tisch Center's researchers and scientists. I’d like to touch on The Tisch Multiple Sclerosis Research Center of New York itself, and some of the other areas of research that are currently ongoing in The Center’s labs. Could you give us a peek inside and tell us about some of the other projects Tisch researchers are working on?

Dr. Sadiq: Well, at the Tisch Center our original goal was to identify the root cause of the disease. It may be some type of immune cell, or some unidentified infectious agent, or maybe some other environmental element. Once we can identify the cause of multiple sclerosis, we can then methodically work towards a cure. And finding a cure is our ultimate goal.

WK: So, the Tisch Center currently has researchers who spend their days searching for the root cause of multiple sclerosis?

Dr. Sadiq: Yes, absolutely. I try to focus on the real challenges that I see as a clinician treating patients every day. My focus is on trying to understand primary progressive MS, which is perhaps the most challenging form of MS as far as treatment is concerned. There are very few treatments that can alter the course of progressive MS. We’ve created an animal model in our lab to try to understand the mechanisms of progression and why remyelination does not take place at all in this form of the disease. In relapsing-remitting MS we see damage occur and then some repairs get made by the body, especially in early disease. This is something not seen in progressive MS. We need to understand the mechanisms of progression better. We are also focused on cognition dysfunction because that can really dehumanize the patients who suffer from severe cognitive deficits.

We are also hard at work identifying biomarkers that can indicate the activity and severity of the disease. We’ve published a lot of papers in this area. We are doing a lot of work on metabolic dysfunction in the central nervous system in MS, and hopefully, that will lead us to readily identify markers that can pinpoint progression and disease activity, which will, in turn, allow us to assess the effectiveness of treatments in individual patients. In conjunction to the Phase 2 stem cell study itself, one of our aims is to analyze the spinal fluid of all of the study participants for markers that may predict which patients are going to get better by Identifying which patients experience actual repair and remyelination. The goal of identifying biomarkers is to be able to tailor treatments to each individual patient, specific to them and the intricacies of their disease. MS is a very heterogeneous illness, meaning that it affects each patient differently. Through the use of biomarkers, we hope to be able to address these differences on a patient by patient basis.

WK: The Tisch Center is not affiliated with any hospital or academic institution, correct, so it’s an entirely independent research entity?

Dr. Sadiq: Yes we are completely independent. We run Tisch like an academic center in every regard. We have guest speakers and all of the activities that would be associated with typical University research centers, but we are not affiliated with any academic centers. We retain absolute independence in choosing our areas of research.

WK: If you don’t have any of these affiliations, how is all of the research we’ve discussed funded?

Dr. Sadiq: We rely entirely on grants and donations. We use almost all the funds raised directly for research. Fully 90% of all monies raised goes directly into research, which is really an extraordinarily high number compared to other organizations. We keep expenses very low, so only a small percentage of funds raised go towards administrative costs and other such overhead. All of our tax forms and documentation in this regard are available online.

WK: My understanding is that you are not currently receiving any funding at all from the National Multiple Sclerosis Society. Is this correct?

Dr. Sadiq: Yes, that's right, we’ve had some bad luck with the MS Society, but they promised to look into our Phase 2 study, and I’m putting in a grant application. Hopefully, this time they’ll get involved.

WK: Obviously, the Tisch family (click here) is involved, but where does the rest of the Center’s funding generally come from?

Dr. Sadiq: The Tisch family is a very big supporter, but so are our patients and their loved ones. We have a very loyal following of patients and their families and other supporters that really enable this to happen. They’ve been supporting us for close to two decades, even before we were formed as an independent center.

WK: How much is this Phase 2 trial going to cost?

Dr. Sadiq: The build-out of the laboratory cost $5 million, and that’s a done deal. The trial itself calls for another $4 million, and we are currently raising funds for the study itself.

WK: So funding is still needed for the Phase 2 trial?

Dr. Sadiq: Yes.

WK: Well, speaking strictly for myself as a patient who has been ravaged by this disease, I can’t think of any cause more important and worthy of donations.

Dr. Sadiq: That’s very kind. Maybe I should hire you as a fundraiser…

WK: You can pay me in stem cells… Even though I know I don’t qualify for the trial because of my  level of disability…

Dr. Sadiq: That’s true, but don’t ever lose hope. Every day researchers here at Tisch and others around the world are working hard towards solving the puzzle of MS. I’m personally obsessed with curing multiple sclerosis.



As a patient of Dr. Sadiq’s, I can attest to his obsession with curing the disease. The man works at least six out of every seven days and even has a bedroom behind his office at the clinic affiliated with the Tisch Center. The clinic is called The International Multiple Sclerosis Management Practice (click here).  I’m also acquainted with some of the researchers at the Tisch Center, who are so dedicated that they'll even put up with my incessant questions when I manage to corner one of them with my wheelchair.

For those interested in donating to the Tisch Center, you can learn about the various ways to contribute by (clicking here). If you’d like to encourage the National Multiple Sclerosis Society to get behind the first ever FDA approved Phase 2 MS stem cell trial with a nice big grant, here’s a webpage with contact info for all of the Society’s senior leadership (click here). Please be polite If you do reach out to the NMSS. As my grandmother always told me, you can catch more flies with honey than you can with vinegar…

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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