Tawil’s Retirement Marks Milestone in Neuromuscular Disease Research and Treatment

Jun. 17, 2024
Work changed lives of individuals and families living with FSHD, periodic paralysis

Rabi Tawil, MD, one of the world’s leading experts in rare neuromuscular diseases, is retiring after more than three decades with the University of Rochester Medical Center (URMC). While a form of periodic paralysis bears his name, for much of his career, Tawil’s focused on facioscapulohumeral muscular dystrophy (FSHD), and his clinical and scientific contributions have brought researchers to the doorstep of new therapies for this disease.

Rabi Tawil, MD

“Rabi’s tenacity and attention to detail helped shaped an extraordinarily productive research program,” said Robert (Berch) Griggs, MD, professor and former chair of the Department of Neurology at URMC. “His clinical acumen and clarity of research design led to his being the lead clinician in the discovery of the causes and clinical characterization of two neuromuscular diseases. Not satisfied with knowing the causes of disease, he has also pioneered the development of treatments and his legacy will be felt by the patients and families impacted by these disorders.”

“Early on Rabi understood that, without solid, well-designed natural history studies for rare diseases, you could not move forward with treatments,” said Robert Holloway, MD, MPH, chair of the URMC Department of Neurology. “He also recognized that research is not a one-person endeavor, and to move forward you need to create collaboration on a national and international level and bring together the expertise to move forward and develop new treatments.”

Andersen-Tawil Syndrome

When Tawil first arrived at URMC in 1988 as a neurology resident, he immediately began working with Griggs, a recognized expert in periodic paralysis sought out by physicians and patients from across the world. Periodic paralysis is a rare neuromuscular disorder which results in episodic attacks of sudden severe muscle weakness and stiffness.

The volume of clinical visits created an opportunity to build a natural history of the disease, and this is when Tawil first noticed that a population of periodic paralysis patients also had abnormal heart rhythms. After publishing a description of these cases, a geneticist in Mexico reached out with an entire family tree of patients with the condition, a break which enabled Tawil and collaborators to isolate the genetic flaw responsible for the condition. These efforts built on earlier work by Danish physician and researcher Ellen Andersen, and the condition was named Andersen-Tawil Syndrome in recognition of their work.

Griggs’ and Tawil’s research in periodic paralysis lay the foundation for clinical trials, and in 2000 the two led a small study showing that the drug dichlorphenamide was highly effective in preventing the attacks and keeping patients’ muscles strong. In 2015, the FDA approved dichlorphenamide for periodic paralysis, making it the first drug to treat the condition.

From Gene Discovery to Drug Development: Trailblazing FSHD Research

While Tawil’s clinical interests also included other neuromuscular disease, such as inclusion body myositis and amyotrophic lateral sclerosis, his special area of expertise for most of his career was FSHD, an inherited disease that causes progressive muscle weakness and degeneration, and affects the muscles in the face, shoulders, upper arms, and lower legs.

Tawil travelled the county to collect clinical information, blood samples, and later muscle biopsies from patients with FSHD. These efforts, which also included the creation of a national registry of patients with the FSHD, provided researchers with the clinical and biological information necessary to study the disease, identify potential therapeutic targets, and recruit patients for clinical trials.

Collaborating with Stephen Tapscott, MD, PhD, with the University of Washington, Silvere van der Maarel, PhD, with Leiden University Medical Center in the Netherlands, and Jeff Statland, MD, a former experimental neurotherapeutics fellow at URMC now with Kansas University, and others, Tawil and his colleagues were able to pinpoint the source of the disease, a gene called DUX4 that is normally inactive in most cells in the body but gets activated in FSHD, and how this mutation gives rise to the disease. Tawil and his collaborators also identified the genetic flaw behind a rarer form of the disease called FSHD type 2.

Tawil helped build an international network of researchers and the tools necessary to carry out clinical trials for FSHD. Earlier this year, Tawil was first author of a study that appeared in the journal Lancet Neurology, which showed that the drug losmapimod improved function in patients with FSHD. Several more drugs are in development for the disease.

“While Rabi leaves the work in FSHD in the hands of collaborators, colleagues, and former mentees, his contributions to this field are immeasurable and have paved the way for new therapies,” said Griggs.

Tawil was born in Syria and received his medical degree from the American University of Beirut. He completed his residency at Good Samaritan Hospital in Baltimore and his neurology residency and neuromuscular disease fellowship at URMC. Since 2016, Tawil has served as the Richard Fields Endowed Professor of Neurology, Pathology and Laboratory Medicine. Over his career, he has authored more than 230 publications and book chapters on neuromuscular disorders. Tawil’s legacy will endure through the many neuromuscular clinicians and researchers he has trained and mentored over his career.