First human trial of gene-silencing therapy launched to treat vision-threatening effects of Bardet-Biedl syndrome

Research at the University of Iowa, Iowa City, helped develop the first-in-human gene therapy treatment for retinal degeneration resulting from mutations in the BBS10 gene, which causes vision loss in Bardet-Biedl syndrome. Three pediatric patients recently received the investigational therapy at St. Helier Hospital in London.

Bardet-Biedl syndrome is a rare inherited disorder that affects multiple organ systems andcausesprogressive vision loss during childhood, according to a press release issued by the University of Iowa, Iowa City. Vision loss is one of the major features of Bardet-Biedl syndrome. Loss of vision occurs as the retinal tissue gradually deteriorates. Problems with night vision become apparent by mid-childhood, followed by blind spots that develop in the peripheral vision. The blind spots enlarge over time and merge to produce tunnel vision. Most people with Bardet-Biedl syndrome also develop blurred central vision and become legally blind by adolescence or early adulthood.¹

This gene therapy study was based on the initial proof-of-concept studies that showed that gene replacement therapy coulddelay retinal degeneration and activate dormant retinal conesin a BBS10 mouse model, according to Arlene V. Drack, MD,Professor ofOphthalmology andVisualSciences andPediatrics in the University of Iowa Carver College of Medicine.

Val C. Sheffield, MD, PhD, Professor of Pediatrics and Ophthalmology and Visual Sciences, at the Carver College of Medicine, identified many of the genes linked to Bardet-Biedl syndrome and developed the BBS10 mouse colony used in the research.

The investigational treatment involves intraoperative delivery of a clinical-grade gene therapy vector to the eye. After treatment, patients travel to the University of Iowa for specialized ophthalmic examinations and functional vision testing to assess the therapy's safety and effects.

"This milestone represents years of collaborative research focused on developinga potentialtreatment for children and families affected by thisdevastatingdisease. We're grateful to the patients, families, philanthropic supporters, research partners, and colleagues, and the lab team including Sajag Bhattarai and post-doctoral scholar Ying Hsu, PhD,whose commitment made it possible to reach this important first step in clinical translation," said Arlene V. Drack, MD, who led the preclinical studies.

Reference

1. MedLine Plus. https://medlineplus.gov/genetics/condition/bardet-biedl-syndrome/