Ongoing clinical research at UNC could lead to a first-of-its-kind enzyme replacement therapy for Hunter syndrome, an ultra-rare disorder that causes progressive multisystem disease and neurologic decline.
The initial results are described in a new article published in the New England Journal of Medicine. The research assesses how an intravenous enzyme replacement therapy that crosses the blood-brain barrier can benefit individuals with Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome. Individuals with MPS II lack an enzyme that breaks down complex sugar waste from cells throughout the body and brain. Current therapies only treat the symptoms of the body and do not reach the brain, so most individuals continue to suffer from severe cognitive decline and an early death in their teenage years.
Joseph Muenzer, MD, PhD, the Director of the Muenzer MPS Research and Treatment Center and the Bryson Distinguished Professor in Pediatric Genetics at the UNC School of Medicine, served as the study's lead investigator for Denali Therapeutics' clinical trial.
Denali's proprietary TransportVehicleTM platform uses the body's natural transport receptors to deliver the enzyme missing in MPS II to the brain. The study drug, known as tividenofusp, alfa, substantially reduces heparan sulfate, a complex sugar that accumulates and causes the brain disease in severe MPS II individuals.
"There is an urgent need for new treatment options to address the full spectrum of severe Hunter syndrome, which includes physical and severe cognitive impairment, such as losing the ability to hear, speak, and walk," said Dr. Muenzer. "This novel treatment should have a profound impact on individuals and families living with this devastating disease."
Kim Stephens, DBA, Executive Director of the Muenzer MPS Research and Treatment Center, is well aware of this devastation. Her son Cole has MPS II.
"I miss hearing his sweet voice the most. He lost the ability to talk six years ago. His last word was 'Mommy.' The possibility of a treatment that crosses the blood-brain barrier is amazing. I don't want any other families to go through what we went through watching Cole's abilities slip away," said Stephens.
Three years ago, Stephens moved to Chapel Hill to become the Executive Director of the Muenzer MPS Center. "We have an academic-based rare-disease center that is a unique example of a comprehensive MPS program that includes education, advocacy, expert patient care, and cutting-edge clinical research," said Stephens.
Dr. Muenzer has dedicated his career to MPS, developing the first mouse model for MPS II at UNC more than 24 years ago. Denali Therapeutics used the UNC MPS II knockout-mouse model to generate preclinical data demonstrating that tividenofusp alfa can cross the blood-brain barrier and reduce heparan sulfate storage in the MPS II mouse brain.
The Muenzer MPS Center has been Dr. Muenzer's dream for the past five to ten years and was made possible by generous gifts from Vaughn and Nancy Bryson.
"The Muenzer MPS Center represents a significant step forward in supporting MPS patients and advancing our understanding of these rare disorders. Our goal is to improve the quality of life for individuals with MPS and their families by providing expert care and fostering research to develop new therapies," said Dr. Muenzer.
The new publication in the New England Journal of Medicine puts the UNC Muenzer MPS Center at the forefront of the MPS clinical care and research community.
