Prednisone may enhance the efficacy of AAV-based gene therapy by reducing the immune response

A new study on gene transfer by administering adeno-associated virus (AAV) genes in skeletal muscle of rhesus macaques showed that oral prednisone reduced AAV immune responses that may weaken gene expression therapeutic transgenic over time. Animals that received prednisone prior to gene therapy had a 60% decrease in immune cell infiltrates, primarily cytotoxic T-cell compounds, according to the study published in Human Gene Therapy, a peer-reviewed journal of Mary Ann Liebert, Inc . The article is available free of charge on the Human Gene Therapy website until July 9, 2017.

Megan Cramer, Ohio State University, Paul Martin, the National Children’s Hospital Research Institute and Ohio State University of Columbus University, and co-authors also reported that AAV-treated muscles had higher levels of a biomarker called PD-L2, can induce programmed death of T cells. Researchers report their findings in the article entitled “Induction of T cell infiltration and programmed death by ligand 2 expression by virus-associated adeno in skeletal muscle Macaque Rhesus and modulation by prednisone. ”

“Prednisone is often used in conjunction with AAV gene therapy in the hope of attenuating detrimental immune responses to the AAV capsid. However, very little is known about the precise immune mechanisms involved in its use, or even whether Is beneficial with different routes from AAV administration, “says Terence R. Flotte, MD, Celia and Isaac Haidak, Professor of Medical Education and Dean, Provost and Deputy Executive Director, University of Massachusetts School of Medicine, Worcester, MA.

The research published in this publication was supported by the National Institutes of Health under the award numbers R01-AR049722 and NS077984. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.