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

doi:10.1016/j.isci.2021.102409

Safety and improved efficacy signals following gene therapy in childhood blindness caused by GUCY2D mutations

iScience. 2021 Apr 11;24(5):102409. doi: 10.1016/j.isci.2021.102409. eCollection 2021 May 21.

Affiliations

¹ Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
² Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA, USA.
³ Pennsylvania College of Optometry, Salus University, Elkins Park, PA, USA.
⁴ Department of Pediatrics, Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL, USA.
⁵ Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida College of Medicine, Gainesville, FL, USA.

Abstract

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.

Keywords: Clinical Finding; Clinical Genetics; Techniques in Genetics.

Safety and improved efficacy signals following gene therapy in childhood blindness caused by GUCY2D mutations

Authors

Affiliations

Abstract

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