Dr. Michael Benatar Honored for Innovative ALS Discoveries

University of Miami Miller School of Medicine neurologist Michael Benatar, M.D., Ph.D., was one of seven researchers who received the Sean M. Healey International Prize for Innovation in ALS at the 34th International Symposium on ALS/MND in Basel, Switzerland.

Neurologist and ALS researcher Dr. Michael Benatar
Miller School neurologist Dr. Michael Benatar has been instrumental in establishing blood neurofilament light (NfL) as a biomarker in ALS therapy development.

This prize recognizes a team of investigators who catalyze exceptional discoveries leading to a transformative advance in therapy development for amyotrophic later sclerosis (ALS).

Dr. Benatar, also the Walter Bradley Chair in ALS Research and executive director of the ALS Center at the Miler School, reflected on the honor.

Why did you and your fellow researchers receive the award?

Our collective research through the years has established blood neurofilament light (NfL) as a biomarker in advancing ALS therapy development. Specifically, NfL has enormous value as a prognostic biomarker, a critical ingredient in enabling more efficient clinical trials.

NfL may also be used as a response biomarker with the potential to predict clinical benefits and to identify those at high genetic risk for developing ALS over the short term.

What does this recognition mean to you?

Our team is extremely grateful to have been selected for this prize at a time of new discoveries and understanding of ALS biology. Our discoveries build upon work by a much larger group of people and laboratories from around the world. In many ways, therefore, we are receiving this award on behalf of all who have contributed to the neurofilament story over many years.

I would also like to thank my colleague, Joanne Wuu, Sc.M., research associate professor of neurology and associate director for research at the ALS Center. Together, Joanne and I lead our ALS research program at the Miller School, and she deserves significant credit for our work that led to this award.

Also, progress in the biomarker field reflects the scientific community’s partnership with those who are living with ALS, the many we have lost to ALS and those living with the threat of future ALS. Their commitment to engage with our research and give their precious time and biological samples is humbling. It is this altruism that will lead us to a world free of ALS.

Why are neurofilaments important in understanding ALS?

Neurofilaments are essential structural components—proteins—in the nervous system. When nerve cells die, as they do in ALS, neurofilament is released into the spinal fluid and the blood. The amount of neurofilament in the blood tells us something important about the speed with which neurons are dying in ALS.

In turn, we can use this information to guide strategies and improve the efficiency with which we work to develop treatments for patients with ALS. One of our most important contributions is showing that NfL is more useful as a drug development tool than phosphorylated neurofilament heavy (pNfH), especially when measured in blood.

We have also shown that NfL concentration predicts the future rate of disease progression, that NfL levels, which are generally stable over time, might be helpful in monitoring response to experimental therapies, and that blood NfL can predict when pre-symptomatic people at genetic risk for ALS are likely to develop disease.

What else have you learned about pre-symptomatic ALS?

Our flagship Pre-Symptomatic Familial ALS (Pre-fALS) study initiated in 2007 focused on the earliest stages of the disease, with the long-term goals of identifying biomarkers that predict who is likely to develop ALS and when, as well as preparing for disease prevention studies.

Through Pre-fALS, we have developed methods for studying pre-symptomatic disease, published guidelines for pre-symptomatic genetic testing and counseling and identified NfL as the first biomarker of pre-symptomatic disease that predicts imminent phenoconversion to clinically manifest ALS. We have also identified mild motor impairment as a prodromal stage of ALS and launched ATLAS, the first ALS prevention trial.

How has your work on neurofilaments impacted development of ALS treatments?

Seven years ago, we published data showing that the concentration of NfL in the blood goes up in people at genetic risk for developing a form of SOD-1 ALS.

Envisioning this as a risk/susceptibility biomarker, we partnered with Biogen to launch the ATLAS trial in which carriers of a pathogenic variant in the SOD1 gene are treated with tofersen, an SOD1-lowering antisense oligonucleotide, before any clinical signs of ALS.

Since then, the FDA has approved the use of tofersen for people already affected with SOD1-ALS. The use of NfL in this way was based, in part, of some of our prior work.

How useful is NfL testing for patients with ALS?

Most of what we know about the use of NfL is based on the study of groups of people. There are still limitations to our understanding of how NfL behaves in an individual person. Any testing for NfL should be done in the hands of an experience clinician who understands how to interpret an NfL test result.

What’s next on the horizon for your research?

We remain very focused on developing biomarkers that can aid the development of treatments for people with ALS. We are also committed to advancing our longstanding goal of ALS prevention, not only in genetic forms of disease, but also for those at risk for non-genetic ALS.

We will soon be launching a study of mild motor impairment in the general community, with the goal of reducing the typical, long delay between symptom onset and diagnosis, thereby creating opportunities for early treatment. 

Who was on the prize-winning global team?

The other team members were:

  • Robert Bowser, Ph.D., chief scientific officer, professor of translational neuroscience, Barrow Neurological Institute
  • Martin Turner, M.B.B.S., Ph.D., professor of clinical neurology and neuroscience, Oxford University
  • Andrea Malaspina, M.B.B.S., Ph.D., professor of neurology, University College of London
  • Markus Otto, M.D., professor of neurology, Martin Luther University Halle-Wittenberg
  • Toby Ferguson, M.D., Ph.D., and Stephanie Fradette, Pharm.D, from Biogen in Cambridge, Massachusetts

Tags: ALS, ALS Center, Dr. Michael Benatar