Authors:
Albert M Maguire MD, Prof Katherine A High MD, Prof Alberto Auricchio MD, J Fraser Wright PhD, Eric A Pierce MD, Francesco Testa MD, Federico Mingozzi PhD, Jeannette L Bennicelli PhD, Gui-shuang Ying PhD, Settimio Rossi MD, Prof Ann Fulton MD, Kathleen A Marshall COT, Sandro Banfi MD, Daniel C Chung DO, Jessica IW Morgan PhD, Bernd Hauck PhD, Olga Zelenaia PhD, Xiaosong Zhu MD, Leslie Raffini MD, Frauke Coppieters PhD, Elfride De Baere PhD, Kenneth S Shindler MD, Prof Nicholas J Volpe MD, Enrico M Surace DVM, Carmela Acerra BA, Arkady Lyubarsky PhD, T Michael Redmond PhD, Prof Edwin Stone MD, Junwei Sun MBA, Jennifer Wellman McDonnell MS, Prof Bart P Leroy MD, Francesca Simonelli MD, Prof Jean Bennett MD
Summary:
Background - Gene therapy has the potential to reverse disease or prevent further deterioration of vision in patients with incurable inherited retinal degeneration. We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis.
Methods - We assessed the retinal and visual function in 12 patients (aged 8—44 years) with RPE65-associated Leber's congenital amaurosis given one subretinal injection of adeno-associated virus (AAV) containing a gene encoding a protein needed for the isomerohydrolase activity of the retinal pigment epithelium (AAV2-hRPE65v2) in the worst eye at low (1•5×1010 vector genomes), medium (4•8×1010 vector genomes), or high dose (1•5×1011 vector genomes) for up to 2 years.
Findings - AAV2-hRPE65v2 was well tolerated and all patients showed sustained improvement in subjective and objective measurements of vision (ie, dark adaptometry, pupillometry, electroretinography, nystagmus, and ambulatory behaviour). Patients had at least a 2 log unit increase in pupillary light responses, and an 8-year-old child had nearly the same level of light sensitivity as that in age-matched normal-sighted individuals. The greatest improvement was noted in children, all of whom gained ambulatory vision.
Interpretation - The safety, extent, and stability of improvement in vision in all patients support the use of AAV-mediated gene therapy for treatment of inherited retinal diseases, with early intervention resulting in the best potential gain.
Source:
The Lancet; Vol. 374, Issue 9701, 1597-1605 (11/07/09)