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As part of the phase 1 clinical trial for patients with Hunter syndrome, Joseph Muenzer, MD, PhD, performed the UNC Clinical Translational and Research Center’s first-ever in vivo genome editing therapy, achieving a milestone in his own career.

Contact: Carleigh Gabryel, 919-864-0580,

CHAPEL HILL, NC – Preliminary safety and efficacy data from the first-ever trial studying an in vivo genome editing therapy have been presented by UNC’s Joseph Muenzer, MD, PhD, at the 2018 Annual Symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) this week in Athens, Greece.

Muenzer, a professor of pediatric genetics and metabolism at the UNC School of Medicine, and a principal investigator of the ongoing CHAMPIONS trial, discussed initial results during the symposium’s Lysosomal Storage Disorders session. The CHAMPIONS trial is an open-label clinical study designed to assess the safety, tolerability and preliminary efficacy of three dose levels of the SB-913 investigational genome editing therapy in up to nine adult males with Hunter syndrome. The SB-913 treatment was developed by biotechnology company Sangamo Therapeutics, which is sponsoring the CHAMPIONS trial that began in May of 2017.

Hunter syndrome (mucopolysaccharidosis Type II) is a rare progressive genetic disorder that primarily affects males and is caused by mutations in the gene encoding the iduronate-2-sulfatase (IDS) enzyme. As a result of the mutations, there is a deficiency of IDS, which is responsible for breaking down large sugars called glycosaminoglycans (GAGs). Hunter syndrome patients see a buildup of GAGs, which leads to tissue and organ damage and dysfunction.

Individuals with Hunter syndrome present with a spectrum of clinical disease, depending on the severity of the mutation and degree of residual enzyme activity. Severe patients develop physical disease, as well as cognitive impairment. Less severe patients never develop cognitive impairment but have significant physical disease that can be very similar to that of severe patients, including short stature, hearing loss, decreased joint range of motion, enlargement of the liver and spleen, obstructive airway disease, cardiac valvular disease, along with significant skeletal issues.

The SB-913 therapy aims to treat the condition by using genome editing to insert a corrective gene into a precise location in the DNA of liver cells with the goal of enabling a patient’s liver to produce a lifelong and stable supply of an enzyme they lack.

At the SSIEM symposium Muenzer discussed preliminary results of two groups of patients in the trial — one that received a low treatment dose and another that received a middle treatment dose.

“While the results are early, we are seeing a dose dependent reduction in large sugars that accumulate inside cells and are the primary biochemical markers of this disease. This is encouraging,” said Muenzer.

Results from a third group receiving a high dose of treatment will not be available until later this year. At that time the study’s safety monitoring committee will review cumulative data from all three dose cohorts. Sangamo plans to present longer-term safety and efficacy results from the CHAMPIONS study in February 2019 at the We’re Organizing Research on Lysosomal Diseases (WORLD) Symposium in Orlando, Florida.