URMC to Lead First Gene Therapy Study for Batten Disease

Nov. 3, 2021

The University of Rochester Medical Center (URMC) will serve as the lead study site in the U.S. for an experimental treatment being developed by Neurogene for CLN5 Batten disease, a rare and fatal neurodegenerative disorder. 

“CLN5 is a devastating and rapidly progressive neurodegenerative disease in children that leads to vision loss, cognitive and motor impairment, seizures and, ultimately, premature death,” said Jonathan W. Mink, M.D., Ph.D., the Frederick A. Horner MD Distinguished Professor in Pediatric Neurology, Chief of Child Neurology at URMC. “This trial will move research forward in developing a potentially disease-modifying treatment for CLN5 disease, providing hope to individuals and families where currently none exists.”

Batten disease is a group of rare, inherited neurodegenerative diseases also called neuronal ceroid lipofuscinoses (NCLs).  The CLN5 subtype is caused by a variants in the CLN5 gene, which leads to disruption of normal protein function.  The disease will often first appear and be diagnosed in childhood.  There are currently no approved treatments that can reverse the symptoms of this disease.

The Medical Center is home to the University of Rochester Batten Center (URBC), which is led by Mink and is one of the nation’s premier centers dedicated to the study and treatment of this condition.  

This clinical trial is possible because of the work started back in 2001 by Mink, URMC neurologist Frederick Marshall, and others to understand the natural history of these complex diseases.  Working with patients from across the U.S., the team created the Unified Batten Disease Rating Scale, which tracks and quantifies how the different forms of disease progress over time.  This tool is employed by researchers across the world to evaluate patients and develop and test new potential therapies.

The planned open-label phase 1/2 clinical trial will evaluate a single intraventricular dose delivered directly into cerebrospinal fluid in the brain. The treatment, called NGN-101, uses an adeno-associated virus to deliver a healthy version of CLN5 gene directly to the central nervous system. Animal studies have shown that the treatment has the potential to halt the key features of disease progression, including vision, motor, cognitive, and behavioral declines.   

“At this point for CLN5 disease, what we can offer patients is limited to managing some of their symptoms, and even standard treatment for symptoms like seizures are not consistently effective,” said Mink.  “This new study also has the potential to inform development of gene therapies for other forms of the disease. It is a moment that the research community and patients and families have been waiting a long time to come.”

Neurogene’s NGN-101 was recently cleared by the Food and Drug Administration to begin clinical trials and has received Orphan Drug Designation by the U.S. and European regulatory agencies.  URMC anticipates enrolling its first study participants in early 2022.  Due to the rare nature of CNL5, Mink anticipates that patients from across the U.S. will travel to Rochester to participate in the study.  Other URMC researchers involved in the clinical trial include Amy Vierhile, D.N.P. Jennifer Vermilion, M.D., Heather Adams, Ph.D., and Erika Augustine, M.D.