Key Takeaways

• University of Iowa research established the preclinical proof of concept supporting a first-in-human gene therapy study for BBS10-associated retinal degeneration
• Three pediatric patients have received the investigational therapy through the United Kingdom's Specials program at St. Helier Hospital in London

Research conducted at the University of Iowa has helped establish the scientific foundation for a first-in-human gene therapy study targeting retinal degeneration caused by mutations in the BBS10 gene, with the first three pediatric patients recently treated in the United Kingdom.

The investigational therapy is designed to address one of the genetic causes of Bardet-Biedl syndrome (BBS), a rare inherited disorder that affects multiple organ systems and leads to progressive vision loss beginning in childhood.

The clinical milestone follows years of preclinical research led by Arlene V. Drack, MD, professor of Ophthalmology and Visual Sciences and Pediatrics at the University of Iowa Carver College of Medicine. Dr. Drack and colleagues demonstrated in proof-of-concept studies that gene replacement therapy could delay retinal degeneration and activate dormant retinal cone cells in a BBS10 mouse model.

That research was supported through philanthropic gifts and funding from InVision2020, Fighting Blindness Canada, the Bardet Biedl Syndrome Association, and the departmental Keech Professorship.

The therapy's development also builds on decades of genetic research by Val C. Sheffield, MD, PhD, professor of Pediatrics and Ophthalmology and Visual Sciences at the University of Iowa Carver College of Medicine. Dr. Sheffield identified many of the genes associated with Bardet-Biedl syndrome and developed the BBS10 mouse colony that served as a key research platform for advancing the therapeutic program.

"This milestone represents years of collaborative research focused on developing a potential treatment for children and families affected by this devastating disease," Dr. Drack said in a University article. "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."

The University of Iowa's preclinical findings established the scientific rationale for continued development of the therapy. London-based biotechnology company MeiraGTx subsequently partnered to develop a clinical-grade gene therapy vector for human use. The resulting vector underwent additional evaluation in both London and Iowa City before entering clinical testing.

The first-in-human study is being conducted through the United Kingdom's Specials program at St. Helier Hospital in London. Three pediatric patients have received the investigational subretinal gene therapy, with procedures performed by retinal surgeon Neruban Kumaran. The study is led by Michel Michaelides.

Following treatment, participants are traveling to Iowa for specialized ophthalmic examinations and functional vision testing intended to provide additional information on the therapy's safety and potential biological effects. The current investigation is designed primarily to assess the safety and feasibility of the investigational gene therapy. Researchers noted that additional studies will be required to determine the treatment's long-term safety and efficacy.