New Grants will Accelerate Clinical Trials in Rare Neurological Disorders

Two new grants from the National Institute of Neurological Disorders and Stroke (NINDS) will pave the way for new treatments for neuronal ceroid lipofuscinoses and Charcot Marie Tooth diseases, two groups of rare neurological disorders.  The funding, which totals $10 million, will support new research programs led by University of Rochester Medical Center (URMC) neurologists Erika Augustine, M.D., and David Herrmann, M.B.B.Ch., and involve an international team of scientists and clinicians.

The funding comes from the NINDS Clinical Trial Readiness for Rare Neurological and Neuromuscular Diseases program, which was created to support studies that lay the groundwork for the next generation of treatments – including gene replacement therapies – currently under development.   URMC researchers play leading roles in three of the five NINDS clinical trial readiness programs.   URMC neurologist Rabi Tawil, M.D., is a co-director of an existing program that focuses on facioscapulohumeral muscular dystrophy.

“For many neurological diseases, there is a lack of preparedness to run the highest quality clinical trials,” said Herrmann. “This includes making sure that you have teams in place and ways to effectively measure the effect of a new drug. And because you're dealing with a rare disease, getting enough patients into a trial is often a challenge.”

“As the pipeline of potential new treatments expands, we have to be ready,” said Augustine. “This means not just understanding the natural history of these disease, but to have clinical trial tools that are fit for purpose, both to meet regulatory requirements and to measure what is important to patients and families.”

The research program led by Augustine will focus on Juvenile neuronal ceroid lipofuscinosis (CLN3 disease) – the most prevalent form of a family of neurological disorders commonly referred to as Batten diseases. The symptoms of CLN3 disease emerge in early childhood and involve vision loss, seizures, and impaired cognitive and motor function, all of which worsen as the disease progresses and youth typically die of disease complications by their twenties or thirties. There are currently no therapies available to modify the course of the disease. 

The new funding will support a partnership between the University of Rochester Batten Center and the University of Hamburg in Germany to validate clinical outcomes and neuroimaging biomarkers that will precisely measure the symptoms and progression of CLN3 Disease and enable researchers to determine if new experimental therapies are effective. This funding builds upon more than 15-years of leading research by the Batten Center, which is directed by Jonathan Mink, M.D., Ph.D., in collaboration with Heather Adams, Ph.D. Frederick Marshall, M.D., Amy Vierhile, P.N.P., and Christopher Beck, Ph.D. 

The program headed by Herrmann, who heads the URMC Neuromuscular Disease Program, will focus on Charcot Marie Tooth disease (CMT), a family of rare inherited peripheral neuropathies that is characterized by progressive weakness, imbalance, sensory loss, and gait abnormalities.   While physical and occupational therapy, braces and other orthopedic devices, and surgery can help individuals cope with the disabling symptoms of the disease, there is currently no disease modifying treatment for CMT.

The project will involve researchers from URMC, the University of Iowa, the University of Pennsylvania, the University of Sydney in Australia, University College of London, and the C. Besta Neurological Institute in Milan, Italy. The team will be validating a clinical outcomes tool and new imaging technologies that measure the integrity and density of muscle tissue and nerve endings.    The goal of the program is to generate a set of biomarkers and patient-centered measures of meaningful functional improvement that can ultimately be used in future clinical trials.