Safety and improved efficacy signals following gene therapy in childhood blindness caused by GUCY2D mutations
Samuel G. Jacobson,
Artur V. Cideciyan,
Allen C. Ho,
Igor V. Peshenko,
Alexandra V. Garafalo,
Alejandro J. Roman,
Alexander Sumaroka,
Vivian Wu,
Arun K. Krishnan,
Rebecca Sheplock,
Sanford L. Boye,
Alexander M. Dizhoor,
Shannon E. Boye
Affiliations
Samuel G. Jacobson
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Corresponding author
Artur V. Cideciyan
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Allen C. Ho
Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA
Igor V. Peshenko
Pennsylvania College of Optometry, Salus University, Elkins Park, PA, USA
Alexandra V. Garafalo
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Alejandro J. Roman
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Alexander Sumaroka
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Vivian Wu
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Arun K. Krishnan
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Rebecca Sheplock
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
Sanford L. Boye
Department of Pediatrics, Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA
Alexander M. Dizhoor
Pennsylvania College of Optometry, Salus University, Elkins Park, PA, USA
Shannon E. Boye
Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida College of Medicine, Gainesville, FL, USA
Summary: A first-in-human clinical trial of gene therapy in Leber congenital amaurosis due to mutations in the GUCY2D gene is underway, and early results are summarized. A recombinant adeno-associated virus serotype 5 (rAAV5) vector carrying the human GUCY2D gene was delivered by subretinal injection to one eye in three adult patients with severe visual loss, nystagmus, but preserved retinal structure. Safety and efficacy parameters were monitored for 9 months post-operatively. No systemic toxicity was detected; there were no serious adverse events, and ocular adverse events resolved. P1 and P2 showed statistically significant rod photoreceptor vision improvement by full-field stimulus testing in the treated eye. P1 also showed improvement in pupillary responses. Visual acuity remained stable from baseline in P1 and P2. P3, however, showed a gain of 0.3 logMAR in the treated eye, indicating greater cone-photoreceptor function. The results show safety and both rod- and cone-mediated efficacy of this therapy.
