Multiple Sclerosis Discovery -- Episode 13 with Professor Alan Thompson

[intro music]   Hello, and welcome to Episode Thirteen of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with Dr. Alan Thompson about the International Progressive MS Alliance, a new collaborative effort to unravel the mysteries of progressive MS. But to begin, here is a brief summary of our time at the ECTRIMS-ACTRIMS meeting in Boston.   The M-S-D-F editorial staff was in full force at MS Boston 2014. We were everywhere covering talks and poster sessions, tweeting up a storm. We live-tweeted the Plenary sessions and most of the talks. If you missed the, or just want to relive the highlights, you can see a roundup of all the best tweets from MS Boston 2014 at our blog on msdiscovery dot o-r-g.   At the meeting we recorded several interviews for future Multiple Sclerosis Discovery podcasts. We’re excited to bring you interviews with researchers, [Dan, name three people you interviewed], and more over the coming weeks and months.   Our parent organization, the Accelerated Cure Project for Multiple Sclerosis –ACP--, also had a booth at the meeting. We really enjoyed meeting many of M-S-D-F’s readers and listeners and telling them more about our organization and our projects. In addition to MSDF, ACP manages a repository of almost 3,000 biological samples from people with Multiple Sclerosis (MS) and other demyelinating diseases, their affected and unaffected relatives, and unaffected, unrelated matched controls. We provide the samples to researchers quickly and at minimal cost. ACP has received funding for a patient-powered research network for multiple sclerosis. We will soon debut the network’s web portal, called iConquerMS. We were especially delighted to announce initial funding from EMD Serono for OPT-UP – which stands for optimizing treatment, understanding progression -- a longitudinal study of 2,000 people with MS. If you missed us, visit accelearatedcure dot o-r-g for more information.   [transition music] Now to the interview. Dr. Alan Thompson is the chair of the scientific steering committee of the International Progressive MS Alliance. At the ECTRIMS-ACTRIMS meeting, the Alliance announced their 22 first-round grant recipients. Dr. Thompson met with science writer Cynthia McKelvey to discuss the challenges in researching progressive MS. Interviewer – Cynthia McKelvey What is the goal of the Progressive MS Alliance?   Interviewee – Dr. Alan Thompson The goal is very simple; it’s to find treatments for progressive MS, probably the most important thing we have to do in the field of MS now.   MSDF We’re at the ACTRIMS and ECTRIMS meeting in Boston, and tomorrow you’re going to announce the first round of grant recipients. What were you trying to accomplish with this first round?   Dr. Thompson Well this, the RFA one as we call it, was really to stimulate interest in progressive MS; so to encourage as many people around the world to put in applications for these relatively small awards – they’re 75,000 Euros – but it was really to stimulate interest. And it certainly succeeded in doing that in that we had 195 applicants, perhaps double of what we thought. And I think what’s also quite unique about this is this is an international initiative, so the review of these awards was done internationally and agreed by this panel, so that they’ll be announced tomorrow. We were initially hoping we would have 15 awards, but we’ve been able to make 22 awards because of A, the quality of the applications, but also the willingness of the executive committee to actually go a little bit further.   MSDF With this first round in terms of the research, what do you hope to accomplish to eliminate some of the mysteries in progressive MS?   Dr. Thompson We’ve identified a number of areas that we feel are absolutely critical if we’re going to actually identify new treatments. The first is around mechanisms underlying progression and thereby identifying potential targets for treatment. Then, of course, there’s the whole issue of biomarkers and evaluating the effect of treatments, setting up new trials in progressive MS. And the other area is around rehabilitation and symptomatic management, which is really critical for people with progressive MS.   And if you look at the range of awards that we’re making, they actually hit all of these areas. So there’s a couple of awards in each one, which is really very reassuring. I mean, I think the hope will be that these could also be the beginning of the major network awards that we’re moving on to in the next phase.   MSDF And my understanding is that in progressive MS, there’s a lot of issues just in doing basic research, and even in moving onto clinical trials. What are some of those issues and how do you propose that research can overcome them?   Dr. Thompson Well, if we look at two areas, I suppose, the first is understanding the basic mechanisms, and what does progression mean, what’s actually happening? Is it driven by inflammation, is it purely neurodegenerative, what’s the combination of those, are there other cells involved like microglia or astrocytes? So there are big questions around mechanisms, which are essential if you’re going to target treatments. And driving that research forward will help us to define new targets. That’s part of the story.   The other large area is then, well, how do you measure effect? And progression goes on over many, many years, it is predominantly neurodegenerative so we need to think about different biomarkers; markers of tissue loss or tissue destruction rather than of inflammation, which is, in many ways, much easier and which we’ve been able to apply in relapsing-remitting MS. So that needs to be resolved. And there’s a lot of imaging work going on, and, indeed, other CSF biomarkers being looked at which might help us in that field.   And then going on to trials themselves. The current approach to trials is very lengthy, very costly, and not very innovative. And we need to think about news ways of looking at a number of different agents at the same time. And there are already examples, both in Europe and in the United States, where we’re starting to do that. So these are all areas where there’s movement. And I suppose what the Alliance has tried to do is really drive that, focus it and drive it forward in a true collaboration.   MSDF So there aren’t currently, at least in the US, any FDA-approved treatments for progressive MS. What specific types of treatments are you focusing on that you think will be most promising?   Dr. Thompson The treatments we have at the moment which we are you using in relapsing-remitting MS are fundamentally around suppressing inflammation, and that does not appear to be sufficient to have an effect on progression, and that’s probably not surprising. So I think the kind of approaches that we need to take with progression is around neuroprotection and also around repair. And these are more challenging; these are more challenging from a neuroscientific point of view, but also more challenging clinically. But that’s where we would expect the new trials to come out of those areas, particularly around neuroprotection.   MSDF Why is it challenging to study that scientifically?   Dr. Thompson Well, because neuroprotection is a concept at repair that we’re thinking about, not just for MS but for a whole range of neurological conditions, including Alzheimer’s, a motor neuron disease. And it’s challenging because you have to understand the underlying mechanisms and then you have to understand how your intervention is going to alter those. And that’s really getting to the heart of some of the most difficult questions in neuroscience.   MSDF It’s also my understanding that even just confirming that any of these drugs actually work in people is another challenge.   Dr. Thompson Yes. I mean, I think confirmation requires, first of all, a really reliable surrogate marker, but it also requires a clinical measure. And when you’re looking at a process which goes on over 30 years, trying to get a snapshot in two or three years is very difficult. And the clinical measures we have in MS are not very sensitive to change, and so there’s another major initiative called MOSAIC which is actually looking at trying to develop more sensitive measures that we could then apply in trials for progressive MS.   MSDF What is the future for the Progressive MS Alliance? How do you propose to go from this first round of grants towards a cure?   Dr. Thompson The Alliance is a new concept, and the idea of everybody working together internationally to solve a really difficult problem is very exciting. The RFA-1 was encouraging because there was so much interest. So it’s quite clear that in every country from North America to Australia, Europe, Asia, everybody feels this is the key question. So what I would like to see happening is we moving from these smaller grants to this international network of grants. So the RFA-2 will require major centers to come together to address very specific questions. Collaboration is the key for difficult questions, so I think this is the right approach.   We’re planning RFA-2 to be very iterative with the scientific steering committee so we can really try and get the very best out of it. This has to be transformational. If RFA-2 is successful and we’re putting three or four major pieces of research forward that will be costing between 4 and 5 million Euros, then we might think about building on that and becoming even more ambitious, drawing in even more resources internationally. And then perhaps – and hopefully – and the final aim, coming up with a treatment for progressive MS. [transition music]   Thank you for listening to Episode Thirteen of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to [email protected].    [outro music]