NeuroVoices: Alessio Travaglia, PhD, on New FNIH Partnership to Accelerate ALS Biomarkers, Research

Alessio Travaglia, PhD

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a devastating neurodegenerative disorder that causes loss of function and progressive weakness with a life expectancy of less than 5 years. There are only a handful of approved therapies, most of which aim to prolong survival and reduce complications from the disease. Drug development has increased in recent years, with several new medications currently in the drug pipeline.

Recently, in late May, the Foundation for the National Institutes of Health (FNIH) announced the launch of a public-private partnership to build the largest data source for ALS and expedite the identification of biomarkers and clinical outcome assessments. Managed by the FNIH, the Accelerating Medicines Partnership in Amyotrophic Lateral Sclerosis (AMP ALS) brings together the resources and expertise of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, the FDA, Critical Path Institute, and other stakeholders from academia, life science companies, foundations, and patient-focused groups. Supported by a combined commitment of approximately $60 million, the hope is that data from this repository will allow for earlier diagnosis and accelerated drug development for people living with the disease.

In efforts to better understand how this partnership will advance the research and care for patients with ALS, NeurologyLive® sat down with Alessio Travaglia, PhD, director of the FNIH, for perspective. Travaglia, a neuroscientist with over 15 years of experience in basic and translational neuroscience, discussed the main goals of the partnership and how they align with major unmet needs in ALS research, as well as how this new databank might ease the process of collecting and comparing information for researchers and pharma companies alike.

NeurologyLive: How did this partnership come about and what are the greatest benefits it brings?

Alessio Travaglia, PhD: The Accelerating Medicines Partnership in Amyotrophic Lateral Sclerosis, or AMP ALS, is the newest AMP in our portfolio. The main goal of this initiative is to centralize and build the largest data source for ALS. Since working with NIH, FDA, and multiple organizations from the non-profit and for-profit side of things, this has come up as the biggest hurdle in ALS research. As you can imagine, right now, Pharma has to go to get data from multiple resources. ALS is a very fragmented field, and it's much easier for an organization to go to just one center place to access all the information with just one click. The other thing that we discuss as a group is we want to have biomarkers to identify patients early, track disease progression, and monitor response to treatment. Related to this topic, it came up that we need to have better clinical outcome assessments that are going to help in clinical trials. I would say that those are the main 3 aims that we are going to try to accomplish with this initiative.

Of the notable researched biomarkers, which hold the most promise?

it's a good question. I think that the NfL (neurofilament light) has received a lot of attention. The FNH is leading a project focused on NfL, and we just received a letter from the FDA for the acceptance of our letter of intent. This is very exciting for the field. Overall, partners believe that NfL is validated enough, and that we should start to look at other biomarkers to focus on. And TDP-43 biology came up as one of the main priorities of the initiative. So, we're going to focus on TDP-43 in general, and the cryptic axons are something that has received a lot of attention from our partners. Most likely, we're going to focus on this in the next years to come.

Are there biomarkers that are more specific to the diagnosis of ALS vs the progression of the disease?

ALS is a very challenging disease, and there is no single organization that can solve or tackle this problem, per se. Personally, I'm very excited that we are all working together through this public-private partnership with NIH, FDA, Critical Path, and all the leading organizations to focus on ALS research. As I mentioned before, biomarkers are one critical element that we want to tackle in the next few years. We will certainly identify more biomarkers and information on which biology we should focus to track: disease progression versus response to treatment versus identification, but it's a little bit early to say, which biomarker is the one that we should focus on.

How do we properly utilize all the resources available from this partnership?

I'm very excited because we have all the right people around the table. We have such a strong brain power, and on top of that, we have people with experience sitting around the table. We meet very frequently every other week to discuss what we should do, what are the priorities that we should focus on, while being nimble and changing our work plan based on new biologists or new area of interest that come. On top of that, again, we take into serious consideration what people living with this experience and what they bring to the table. The entire initiative is shaped based on their suggested feedback.

Are there ways in which we can get more creative with drug development for ALS?

All the work that we do is in the pre-competitive space, meaning that everybody can access the resources that we're going to put together. The ALS research base is very fragmented, meaning that each researcher from academia or industry has to go to database A and then compare the result with database B and C and so on. That's a lot of time spent, and sometimes it doesn't bring the outcome that people would like to receive and see. With the ALS knowledge platform, we think that we're going to build a single repository of information where people can go access all the resources out there for ALS research. This means that it's going to be much faster and easier for researchers from academia and industry to analyze all this data out there, and out of these, we really think that we are going to have novel biomarkers identified through the initiative, as well as other targets that are going to expedite the development to drugs to patients.

Do you and your colleagues have any major goals for this new partnership?

In the long run, we're going to stop working on ALS once we find a cure for this horrible disease, that's the vision. That's what we want to accomplish at the end of the day. Within five years, we will certainly put together this ALS knowledge platform. We plan to validate and identify novel biomarkers for ALS research, and we plan to have new clinical outcome assessments that could be tested in clinical trials as well.

Transcript edited for clarity.