The Bombay Technologist

A Hope for Vision:Gene-Replacement Therapy for RPE65 Associated Leber's Congenital Amaurosis

Manish Gore

Bachelor of Pharmacy, Department of Pharmaceutical Sciences and Technology

Nivedita Hegdekar

Bachelor of Pharmacy, Department of Pharmaceutical Sciences and Technology

Keywords: Leber’s Congenital Amaurosis (LCA) Type 2, Rpe65 Gene, Gene Replacement Therapy, Adeno-Associated Virus, Subretinal Delivery, Efficacy, Safety.

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Abstract

Leber's Congenital Amaurosis (LCA) is a group of inherited blinding diseases which leads to congenital retinal dystrophies and is difficult to treat. However, gene replacement therapy holds great potential in treating LCA type 2 caused to Rpe65 gene mutations. This restores the isomerohydrolase activity of the expressed RPE65 protein by correcting the defect at the molecular level. Adeno-Associated Virus mediated subretinal delivery of RPE65 cDNA regulated by constitutive or tissue specific promoter shows dramatic improvement in vision in terms of subjective and objective aspects which indicates efficacy of the therapy. Absence of immune responses, adverse effects and vector dissemination underlines the safety of the therapy. Successful findings observed in pre-clinical and clinical trials pave a way to its practical application. Response to the treatment however varies with the extent of retinal degeneration and age of the patient. Moreover, currently developing non-viral gene delivery and nanoparticle mediated approaches gives an insight to its future prospects too.