Research conducted at the University of Iowa helped lay the scientific foundation for a first-in-human gene therapy study that recently treated its first three patients in the United Kingdom.
The investigational therapy targets retinal degeneration caused by mutations in the BBS10 gene, one of the genetic causes of Bardet-Biedl syndrome (BBS), a rare inherited disorder that affects multiple organ systems and causes progressive vision loss in childhood.
Arlene V. Drack, MD, Professor of Ophthalmology and Visual Sciences and Pediatrics in the UI Carver College of Medicine, and her team, conducted the initial proof-of-concept studies demonstrating that gene replacement therapy could delay retinal degeneration and activate dormant retinal cones in the BBS10 mouse model. The preclinical work was supported by philanthropic gifts and funding from InVision2020, Fighting Blindness Canada, the Bardet Biedl Syndrome Association, and the departmental Keech Professorship.
The therapy's development builds on decades of research at the University of Iowa. Val C. Sheffield, MD, PhD, Professor of Pediatrics and Ophthalmology and Visual Sciences in the UI Carver College of Medicine, identified many of the genes associated with Bardet-Biedl syndrome and developed the BBS10 mouse colony that became instrumental in advancing the research. "This milestone represents years of collaborative research focused on developing a potential treatment for children and families affected by this devastating disease," Drack said. "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 research established the scientific rationale for continued development of the therapy. MeiraGTx, a London-based biotechnology company, partnered to develop a clinical-grade gene therapy vector for human use, with the resulting vector studied in both London and Iowa City. The first-in-human study was conducted through the United Kingdom's Specials program at St. Helier Hospital in London, where three pediatric patients recently received the investigational treatment by surgeon Neruban Kumaran. The London study is helmed by Michel Michaelides.
While the procedures were performed in London, the University of Iowa continues to play an important role in the study. Patients are traveling to Iowa for specialized ophthalmic examinations and functional vision testing following treatment, providing additional information about the therapy's safety and potential effects.
The current study is designed to evaluate the safety and feasibility of the investigational therapy. Additional research will be needed to determine its long-term safety and effectiveness.
This work highlights the role of academic research in advancing discoveries from the laboratory toward potential new treatments for patients with rare inherited retinal diseases through collaborations among university investigators, philanthropic supporters, and industry partners.