Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis

• DOI: 10.1056/nejmoa0802315
• Publication Date: 2008-04-28T00:12:57Z
• Authors: Albert M. Maguire; Francesca Simonelli; Eric A. Pierce; Edward N. Pugh; Federico Mingozzi; Jeannette Bennicelli; Sandro Banfi; Kathleen A. Marshall; Francesco Testa; Enrico M. Surace; Settimio Rossi; Arkady Lyubarsky; Valder R. Arruda; Barbara Konkle; Edwin Stone; Junwei Sun; Jonathan Jacobs; Lou Dell'Osso; Richard Hertle; Jian-xing Ma; T. Michael Redmond; Xiaosong Zhu; Bernd Hauck; Olga Zelenaia; Kenneth S. Shindler; Maureen G. Maguire; J. Fraser Wright; Nicholas J. Volpe; Jennifer Wellman ...; Alberto Auricchio; Katherine A. High; Jean Bennett
• Keywords: Adult; cis-trans-Isomerases; 0301 basic medicine; DNA, Complementary; Genetic Vectors; Retinal Degeneration; Gene Transfer Techniques; Visual Acuity; Genetic Therapy; Dependovirus; Blindness; Reflex, Pupillary; Retina; Injections; 3. Good health; 03 medical and health sciences; Mutation; Humans; Carrier Proteins; Eye Proteins; Promoter Regions, Genetic

Leber's congenital amaurosis (LCA) is a group of inherited blinding diseases with onset during childhood. One form of the disease, LCA2, is caused by mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65). We investigated the safety of subretinal delivery of a recombinant adeno-associated virus (AAV) carrying RPE65 complementary DNA (cDNA) (ClinicalTrials.gov number, NCT00516477 [ClinicalTrials.gov]). Three patients with LCA2 had an acceptable local and systemic adverse-event profile after delivery of AAV2.hRPE65v2. Each patient had a modest improvement in measures of retinal function on subjective tests of visual acuity. In one patient, an asymptomatic macular hole developed, and although the occurrence was considered to be an adverse event, the patient had some return of retinal function. Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA.