In some dramatic news regarding stem cell treatments for Multiple Sclerosis, the FDA has given its first ever approval for a Phase II Multiple Sclerosis regenerative stem cell trial to the Tisch MS Research Center of New York.
Most previous attempts at using stem cells to repair MS damage have involved intravenously infusing a basic type of stem cell (called mesenchymal stem cells) back into the patient from which they were taken. The Tisch Center (click here) takes this approach several steps further, using proprietary methods to transform raw mesenchymal stem cells into a type of stem cell known as neural progenitors, which are specific to the central nervous system. The cells are then injected directly into the spinal fluid of trial subjects, where, in theory, they should be more effective than raw mesenchymal stem cells at effecting repairs and combating the disease. The Phase I results of the Tisch center’s trial thus far have been quite impressive, offering MS patients worldwide a glimpse into the future of MS treatments and some tangible reasons for hope.
A press release put out by the Tisch Center provides details on what has already been accomplished in the Phase I trial, and what is being planned for the upcoming Phase II study:
“Our unprecedented Phase I results have propelled us into the next phase of research,” said Dr. Saud A. Sadiq, Chief Research Scientist at Tisch MSRCNY and the study’s principal investigator. He added, “No treatment has shown reversal of established disability until now. The objective improvement experienced in bladder function, vision and walking speed in both secondary and primary progressive MS is remarkable. We now plan to establish efficacy of stem cells as a reparative therapy in Phase II.”
The Phase II trial will be a double-blind, placebo-controlled, randomized trial with forty patients in a crossover design. Stem cells are taken from the patient’s bone marrow and manipulated to become brain-like neural cells, a process created and found only at Tisch MSRCNY. All treatments and research will be conducted at the Tisch MS Research Center of New York and will expand to include an additional leading MS center.
The main obstacle in intiating the study is the need for critical funding. Once funding is obtained, patients will be recruited and the study is anticipated to commence in the summer of 2016.
I had the chance to talk with Dr. Sadiq (who just so happens to be my MS neurologist) about this ongoing and groundbreaking MS stem cell trial, as well as other stem cell related topics. The following interview has been lightly edited for clarity…
How long did it take the Tisch Center laboratories to develop the proprietary process to produce neural progenitor cells from raw mesenchymal stem cells?
Dr. Sadiq: It took about 2 ½ years of intensive lab work, and our lab is the only lab in the world currently using this process.
Is this type of stem cell treatment considered a cure, or can patients expect to require repeated treatments in order to maintain whatever benefits they achieve?
Dr. Sadiq: All of this is still in the experimental phases, so we really don’t know how long the treatments will need to be continued in order to maintain benefit. It’s likely there will be an initial induction period where we will do a number of frequent treatments to induce repair and then to maintain the benefits I think it will require less frequent treatments. But I anticipate that some treatments will need to be given for the duration of the illness, until we find the cure.
What was the treatment protocol during the Phase I trial, and what will the treatment protocol be during the Phase II trial?
Dr. Sadiq: In Phase I we did three treatments over the course of one year, which seemed necessary in order to get some benefit. We don’t know whether the Phase I patients will continue to show benefit or not without further treatment. In the Phase II trial, we are proposing six treatments over a year followed by no treatments over a year to see if benefits are sustained. There will be a control group as well, who will get no treatments the first year and then get six treatments the second year. I anticipate less frequent treatments will be needed to maintain benefit for the duration of the disease until we find a cure.
And would this hold true for any type of regenerative stem cell treatment, such as those being offered by some of the for-profit clinics at which many patients are seeking a single treatment or a single round of treatments over a relatively short period of time?
Dr. Sadiq: Most likely yes, it’s been shown that one treatment probably would be insufficient to even start regeneration. You’ll need multiple treatments…
Are the effects of the regenerative stem cell treatments cumulative?
Dr. Sadiq: You know, we don’t know that yet, in the Phase II trial we intend to collect data on this question…
How much more effective are the neural progenitor cells than the raw mesenchymal stem cells (MSCs) that have been used in other trials?
Dr. Sadiq: Well, as far as I’m aware, the way MSCs have been used in trials so far, there’s not been a single trial that has shown real substantial benefit with MSCs. There’s been some very mild improvements seen in the Cambridge trials, which used one dose given intravenously. It could be that they didn’t use fresh cells or they didn’t use the proper route of administration. Our trial administers the cells intrathecally, directly into the spinal canal. It could be that raw MSCs are in fact effective, but the trials I’ve seen didn’t use multiple dosing. So it’s very difficult to compare the two. But in our hands we found that neural progenitor cells given intrathecally are more effective than raw MSCs.
How much funding is needed for the Phase II trial?
Dr. Sadiq: For the Phase II trial alone we need about $3 million, but for the actual support that we need to build out and expand the labs I’m looking to get $10 million. We need expanded lab facilities and an animal testing facility in place to properly conduct the Phase II trials.
And how much money have you already raised?
Dr. Sadiq: Planning for Phase II we just started, so we haven’t raised anything yet. We have talked to the National Multiple Sclerosis Society, we’ve talked to the National Institutes of Health. We are submitting a grant proposal to the NIH, and the MS Society Is in consultation with me currently to try to arrange funding. We’ll will have to apply for funding grant from the NMSS. We do have a pledge of about $3 million from one donor.
Wow, you have a pledge of $3 million from one donor?
Dr. Sadiq: Yes.
Is the Phase II trial on hold until all of the funding is in place?
Dr. Sadiq: The trial is not on hold, we are really just starting to think about implementation. We just received FDA approval, and we are going to get another MS center involved, I’m in talks with another MS center here in New York, and then after they’re on board we will get things going. So even if we got all the funding right now, we wouldn’t be able to start the trial until late summer 2016. Right now were planning on starting the trial in July or August 2016.
Assuming everything goes as planned, and there aren’t any unforeseen problems, how long do you think it would be until the type of treatment you are trialing would reach common clinical practice?
Dr. Sadiq: It will probably be by the end of the decade, by 2020 I hope if everything goes well.
Do you think there’s any difference in effectiveness between bone marrow derived and adipose (fat cell) derived stem cells?
Dr. Sadiq: Well, we’re not sure. We started working with bone marrow derived cells from the beginning, but adipose derived may turn out to be better because adipose tissues contain a greater number of MSCs, so you may be able to get a better harvest. But because the FDA oversees every project from start to finish, and our trials began using bone marrow derived cells, if we started using adipose cells now we have to go back to the drawing board with the FDA. So in order to continue our ongoing trial protocols, since we started with bone marrow derived cells, we will continue using bone marrow derived cells.
Do you have any thoughts on the clinics that are currently doing mini liposuctions and then re-injecting the cells intravenously the same day or the day after?
Dr. Sadiq: These clinics are just using the stromal fraction, and nobody really knows what that achieves. This process is really not a stem cell therapy, since the stromal fraction only includes a small number of MSCs. It seems like these clinics just want to make money, there’s no evidence that this method would be effective, at least when dealing with neurodegeneration.
What other avenues of research are being pursued in the Tisch MS center’s labs that you consider most promising?
Dr. Sadiq: My goal in life is to find the cause of MS, and that’s really where I concentrate my efforts. I think we have a number of discoveries that are coming together now and I hope that one day soon we will be able to declare that we’ve found the cause of MS.
We do a lot of work with biomarkers as well. In this Phase II trial we are going to look at all the biomarkers that are associated with clinical response, to be able to identify a marker that will be able to predict which patients have the best chance of responding and seeing benefit, and through what mechanisms they are getting better. This is very important work but it’s not the work that drives me to come into the clinic every day at 4 AM.
What does drive you to come to work every day at four in the morning?
Dr. Sadiq: That’s to find the cure to this damned disease.
I can personally attest to Dr. Sadiq’s obsession with finding the cause of and cure for MS. Through the years, Dr. Sadiq and I have developed quite a strong bond, and I know from experience that he can be found hard at work in his clinic and laboratory nearly round the clock, very often at least six days a week. I’ve spoken to Dr. Sadiq via telephone at all hours of the day and night, and have even had office visits with him on the day after Christmas. He once showed up at my bedside at 3 AM when I was hospitalized and suffering miserably from MS related symptoms, to simply be there with me and literally hold my hand. Not your typical doctor, to be sure.
As Dr. Sadiq makes clear, funding is of the utmost importance in order to get this trial up and running in as timely a fashion as possible. There is a tremendous amount of work to be done, and all donations, no matter how small, will make a difference.
As a long-suffering MS patient myself, I know that friends and family are often eager for ways to help fight the disease. While there are many worthy MS charities, in my opinion the biggest bang for the MS donation buck can be had by donating to the Tisch MS Research Center of New York. Donations to the Tisch Center will directly serve to hasten the completion of these stem cell trials and hopefully bring this exciting technology to MS patients worldwide. Please pass the word along, and (click here) to donate.
A big thank you to all who participate in and contribute to this project, and to all the Wheelchair Kamikaze readers that have made their voices heard at the NMSS in regard to funding the Tisch Center’s efforts. It appears that the MS Society may finally be ready to listen, and hopefully the NMSS will this time come through with funding for this vital research.
I’ll keep you posted…
This article was originally published on Marc’s website on 01/18/16 and is being featured on MultipleSclerosis.net with his permission.