NeuroVoices: Bruce Bebo, PhD, on Expanding MS Research Through the Pathways to Cures Roadmap

Bruce Bebo, PhD

Recently, the National MS Society announced a $19.4 million commitment toward the society’s Pathways to Cures Research Roadmap, a large-scale initiative with the hopes of accelerating scientific breakthroughs to cure multiple sclerosis (MS). The new projects included 15 new research grants, 29 new fellowships and early career awards to support the MS workforce, and 2 strategic initiatives to extend knowledge to be gained from 2 clinical trials which leveraged $24 million in previous investments from the federal government.

Over the years, there have been several significant advances in the treatment and quality of life for patients with MS; however, there are still several unmet needs, including those with more progressive forms of the disease. MS remains a growing health challenge, affecting nearly 3 million people with significant public health and economic impacts. Furthermore, there are several unanswered questions regarding the pathological processes driving disease and the effective ways to optimize treatment selection.

To learn more about Pathways to Cures, and how this recent commitment will be used, NeurologyLive® sat down with Bruce Bebo, PhD, executive vice president of the organization. As part of a new iteration of NeuroVoices, Bebo discussed the 3 distinct but overlapping cure patterns the initiative focuses on, including the research and approaches geared toward stopping disease progression and remyelination.

NeurologyLive^®: What is the Pathways to Cures roadmap, and how will this recent grant be used?

Bruce Bebo, PhD: One could argue that we've made more progress in the understanding and treatment of MS than in many, if not all other neurological conditions. This is what has inspired us to chart this initiative called Pathways to Cures. The goal of the initiative is to establish a clear vision of the most promising areas of research that we think are going to lead us to cures for everyone with MS. Also, to inspire the global MS movement, inspire us to collaborate, to coordinate our research investments on a scale that's unprecedented. That's really what Pathways to Cures was designed to do. In a short amount of time, the roadmap was published in the Multiple Sclerosis Journal last year, and it's received 30 endorsements from global MS organizations, patient advocacy organizations, and professional organizations.

There are 3 cure pathways described in the roadmap. They include stopping MS, restoring function, and ending MS. Stopping [MS] for the purposes of the roadmap is defined as achieving a state of no new disease activity, which could be demonstrated clinically or radiologically. The restore pathway is defined as reversing symptoms and recovering functions so people can have full participation in their lives. The end [MS] pathway is defined as no new cases. Perhaps another way of stating this is prevention. We recently committed $19 million to launch 40 new multiyear research awards. This is part of the society's ongoing commitment to support the research workforce and to really drive progress and pathways to cure. These awards included new training awards, fellowships and junior faculty awards, new research grants, and some strategic initiatives, as well. It adds to our total multiyear commitment of MS research that's around $70 million.

How are we working towards stopping the MS disease process?

As I said, the goal of the pathway is to achieve a state of no more disease activity. This is a strategy that we're focused on. There's two objectives within that pathway: one is early detection, early diagnosis and treatment, perhaps maybe even before the clinical symptoms of MS become apparent, and the other is more precision medicine. Let's start with this early detection. We’re encouraged by the progress that’s been made in other chronic autoimmune diseases like type 1 diabetes and rheumatoid arthritis, the concept of MS being preventable disease, and we've seen a lot of progress being made in The discovery and development of ways to identify people and treat people at the very beginning of their journey with MS.

We’ve learned, for example, at the [American] Academy [of Neurology] Meeting earlier this year that the disease-modifying therapy approved for MS called teriflunomide (Aubagio; Sanofi) could reduce the risk of developing MS in a cohort of people that didn't have any symptoms, but had radiological signs of MS. This is phenomena called radiologically isolated syndrome. It could reduce the conversion from radiologically isolated syndrome to MS by over 70%. This was the second study to show a significant reduction in the risk of developing MS in an RIS cohort.

The ARISE study that was published I think, last year, also reported that treatment with another disease modifying agent, dimethyl fumarate (Tecfidera; Biogen), could reduce the risk for people developing clinical MS by over 80%. I’m also very encouraged by the potential to be able to tailor treatments to individuals with MS based on their unique characteristics. This is the second objective in that stop pathway. A few weeks ago, the genes that regulate the severity of MS or some of the risk variants that may be regulating the severity of MS, were discovered. That study revealed some pathways that we could potentially leverage for new effective treatments for progressive MS, but also could potentially predict the course of disease and [help] inform decisions that can be made early on in the course of the disease that we think would result in better outcomes for people with MS.

Are there remyelinating/demyelinating approaches that seem promising? Others that we know don’t work?

We’ve seen a lot of progress in our understanding of the potential of the central nervous system to repair myelin and some of those pathways can be addressed pharmacologically. Some trials have been performed using agents that block inhibitors of remyelination, sort of this concept of “the enemy of my enemy is my friend.” This is something like Anti-LINGO-1, which some people remember that program. There are other pathways that could promote oligodendrocyte precursor cell differentiation, things like Clemastine. There are cell-based approaches that are showing some promise as well.

Early trials of promyelinating agents have shown that remyelination in humans is possible, I think the roadblock is demonstrating the clinical benefit of those approaches. There's a lot of work going on right now in determining what's the best timing for treatment, the best dose, best methodology for measuring myelin repair in humans. There is no shortage of targets for myelin repair strategies, where I see that roadblock is being able to measure myelin repair and then measuring the clinical benefit of myelin repair in a timeframe that works for clinical trial. Right now, we've measured myelin repair in the visual system, we’ve seen reduction in the latencies of visual-evoked potentials in people that have optic neuritis. What we need are better imaging techniques, and perhaps even biomarkers that can tell us in a quick and early way whether a strategy, pharmacological or otherwise, it's actually having a beneficial effect on myelin repair. I think we also need a better sense of what to look for clinically, and we'll need that to work that out before we'll have an agent that's widely available that’s focused on myelin repair.

Transcript edited for clarity. Click here for more iterations of NeuroVoices.