Clinical Pharmacology Perspective on Development of Adeno-Associated Virus Vector-Based Retina Gene Therapy.

Autor: Ford JL; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Karatza E; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Mody H; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Nagaraja Shastri P; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Khajeh Pour S; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Yang TY; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Swanson M; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Chao D; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA., Devineni D; Janssen Research & Development, LLC, Spring House, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2024 Jun; Vol. 115 (6), pp. 1212-1232. Date of Electronic Publication: 2024 Mar 07.
DOI: 10.1002/cpt.3230
Abstrakt: Adeno-associated virus (AAV) vector-based gene therapy is an innovative modality being increasingly investigated to treat diseases by modifying or replacing defective genes or expressing therapeutic entities. With its unique anatomic and physiological characteristics, the eye constitutes a very attractive target for gene therapy. Specifically, the ocular space is easily accessible and is generally considered "immune-privileged" with a low risk of systemic side effects following local drug administration. As retina cells have limited cellular turnover, a one-time gene delivery has the potential to provide long-term transgene expression. Despite the initial success with voretigene neparvovec (Luxturna), the first approved retina gene therapy, there are still challenges to be overcome for successful clinical development of these products and scientific questions to be answered. The current review paper aims to integrate published experience learned thus far for AAV-based retina gene therapy related to preclinical to clinical translation; first-in-human dose selection; relevant bioanalytical assays and strategies; clinical development considerations including trial design, biodistribution and vector shedding, immunogenicity, transgene expression, and pediatric populations; opportunities for model-informed drug development; and regulatory perspectives. The information presented herein is intended to serve as a guide to inform the clinical development strategy for retina gene therapy with a focus on clinical pharmacology.
(© 2024 Janssen Research & Development. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
Databáze: MEDLINE
Externí odkaz: