Mesenchymal Stem Cell Trial for MS

INTERVIEW WITH DR VIOLAINE HARRIS – SENIOR RESEARCH SCIENTIST, TISCH MS RESEARCH CENTER

BD: Brett Drummond, MStranslate
VH: Dr Violaine Harris, Tisch MS Research Center

BD:  Welcome everyone to our video interview today with Dr Harris from the Tisch MS Research Center in New York.  You may remember that we’ve previously talked about the Tisch MS Research Center in terms of their stem cell therapy that they are working on for people with MS.  Off the back of those stories, we’ve found that people are really interested in the work that they are doing, so we got in contact with Tisch and they’ve kindly agreed to give up their time to do an interview today.  So it’s my pleasure to introduce Dr Harris.  Dr Harris, would you mind starting by just giving us a brief introduction to yourself and telling us a bit about the Tisch MS Research Center?

VH:  Sure, first of all, thank you for having me.  My name is Dr Violaine Harris, I’m a senior researcher here at the Tisch MS Research Center of New York in New York City.  The Tisch Center was started about 10 years ago by Dr Saud Sadiq, who is an MS doctor and has been doing MS research at other institutes and really started this center to facilitate translational research.  The thing that is unique about the Tisch Center is that we are located in close proximity to a world-renowned MS clinic and this enables really the kind of translational research that I think is exemplified in our stem cell trial.  So there is constant collaboration between physicians and scientists and I think that that really accelerates the pace of discovery at the Tisch Center.

BD:  Fantastic!  So you mentioned the stem cell trial and obviously that’s what we have covered briefly on MStranslate, can you talk to us a little bit about that project?

VH:  Yeah, so it started well over 10 years ago.  Then when I joined the lab, we really set out with the objective of using stem cells to repair damage in the brain and spinal cord in MS with the really lofty goal of not only preventing further damage and further disability, but really reversing established disability.  So we started looking at bone marrow stem cells.  The attractive thing about bone marrow stem cells, of course, is that they can be used autologously, so you can use a patient’s own stem cells.  Within bone marrow, we have different types of stem cells, one in particular called mesenchymal stem cells, which are interesting because of their unique properties in terms of tissue damage.  So as we started studying mesenchymal stem cells or MSC’s, we were eventually able to convert them into a neural progenitor population of cells, so brain-like cell populations and we call these mesenchymal stem cell derived neural progenitors (or MSCNPs).

We noticed early on that these cells not only have repair properties, so they secrete a number of growth factors that can influence tissue repair, they also secrete factors that can modulate the immune response.  So one of the kind of landmark experiments that we did was in an animal model, the EAE animal model of MS which is well known, and we let the mice basically develop disease and develop a sort of chronic form of the disease.  Then we injected the MSCNP cells intrathecally into the mice, so that’s in the spinal fluid in the space that surrounds the brain and spinal cord.  We were able to reverse some of the chronic disability in the mice.  One thing we noticed was that a single injection was not effective, the protocol required three injections, spaced about a week apart in the mice, in order to achieve some therapeutic benefit.

Based on the dosing and the dosing regimen in that mouse experiment, we were able to after many years convince the FDA to approve a Phase I clinical trial and that is going on now.  Twenty patients have so far been treated with their own autologous MSCNPs.  They each get a dose of 10 million cells by intrathecal injection and the doses are spaced three months apart.  This is a safety trial, so we are really looking to see if there are any adverse events, which there have not been so far.  What is encouraging is that some patients are having some benefit in various areas, including some improvements in motor strength, improvements in bladder function and so on.  So about 70% of patients in the trial so far have shown some improvement.  Of course, this is not a placebo controlled trial, but it is encouraging nonetheless.

BD:  Yeah certainly and we just recently featured the fact that you’ve received FDA approval now to move onto a Phase II trial for this treatment?  That’s fantastic news.

VH:  That’s right.  So we’ve gotten the green light from the FDA.  At this point, we are in the planning phase, planning the trial, trying to get funding for the trial.  We have started a collaboration with Weill Cornell Medical Center (also here in New York City) to add another site, another clinical site for the trial.  We hope that within the next 6 months we can have some more definitive timelines for the Phase II.

BD:  Excellent, excellent.  I guess one of the things, stem cells have been a buzz word in MS research and across the MS community for really the past 12-24 months, mostly in terms of HSCT.  Can you talk a little bit about how, to help people’s understanding, how what you are doing differs from HSCT?

VH:  Yeah, that’s probably the most frequent question that we get when we talk about this.  So HSCT of course also involves a bone marrow stem cell population, but the purpose of HSCT is really to reboot the immune system.  So it’s really getting at the heart of the autoimmunity, the trigger of MS.  It’s really intended for aggressive, early disease.  What we’re focused on…so first of all, the stem cells that we derive from the bone marrow are a different type of stem cell, a mesenchymal stem cell, not a haematopoietic stem cell.   Haematopoietic stem cells form immune cells, mesenchymal stem cells form cells of the mesenchymal lineage, such as bone and fat and cartilage.  Secondly, we are focused on not modulating the autoimmunity, but we are focused on repairing central nervous system tissue, so remyelination, regeneration of nerves and so on.  So it’s really intended for more progressive forms of the disease.

BD:  So in your trials, obviously you are only in the Phase I stage at the moment, but in the planning stage for the Phase II, do you see this as having…are you just going to be looking at certain subsets of MS or will this be looking at relapsing-remitting, secondary progressive patients?  Will anyone be eligible?

VH:  In the Phase I, we only included progressive patients, but we included patients with a range of disabilities.  If you are familiar with EDSS, it was between 3.5 and 8.0, so different ranges of ambulation in the patient cohort.  For the Phase II, we will probably also only include progressive MS patients, but we may include some that are sort of a borderline relapsing-remitting/secondary progressive.  So that’s still in the planning stages and will be based on the outcomes of the Phase I.

BD:  Fantastic.  So we are going to be broadcasting this out to a wide range of people with MS in our communities across a variety of platforms.  In the stage that you are at, finishing up a Phase I trial and going into a Phase II trial, how can people with MS help support the work that you are doing?

VH:  The funding model at the Tisch Center has always been a mixture of grant support and private sources, so patient donations really forms a big part of our research income.  A project like this wouldn’t have been possible without the patient donations that we’ve been able to receive.  As we move into a Phase II, obviously the costs go way up and we will be applying for funding from the National MS Society and NIH and so on, but we really do depend on patient donations for additional support and without which I don’t think we could move forward in the way we would like to.

BD:  I think from one of my earlier conversations with another member of the team there, she told me that the Phase I trial, the crowdfunding for that was one of the largest ever generated for a medical research project.

VH:  Yeah, it was exciting.  We did a, similar to a Kickstarter, an Indiegogo campaign and we raised over $300,000 in a very short amount of time.  We have a lot of patient support and it really has enabled us to get to this point.  You know, a lot of people consider a stem cell treatment to be very risky and not fundable and we really couldn’t have done it without the patient support.

BD:  I think this is something that we’ve been talking about a little bit recently on MStranslate of the power that the community actually has to really drive research forward.  Not only with funding and helping support projects that they think should be continuing, but also just in terms of how they go about talking about projects online and providing feedback.  That can really drive research projects forward.  It’s really interesting to hear you say that.  Alright, thank you, I think that should give people a great insight into the work you are doing.  We’re hoping to provide more research updates on the work you are doing as they progress.  Thank you so much for your time, we really appreciate it and we hope to talk again soon.

VH:  Ok thank you, I’m happy to participate in this website, I think it’s a great thing, so thank you for inviting me.

BD:  Thanks very much, talk soon!