Steroids may up effectiveness of AAV-based gene therapy

Washington: Glucocorticoid steroids, such as prednisone, may improve effectiveness of AAV-based gene therapy by reducing immune response, according to a recent research.
The study of gene transfer using adeno-associated virus (AAV)-based gene delivery into skeletal muscle of rhesus macaques showed that oral prednisone reduced immune responses to AAV that can weaken expression of the therapeutic transgene over time.

Animals given prednisone before the gene therapy had a 60% decrease in immune cell infiltrates, mainly comprised of cytotoxic T cells, according to the study.

Megan Cramer, The Ohio State University, Paul Martin, The Research Institute at Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, and coauthors also reported that AAV-treated muscles had higher levels of a biomarker called PD-L2, which can induce programmed T-cell death.

“Prednisone is frequently used in conjunction with AAV gene therapy in the hope of blunting harmful immune responses to the AAV capsid. However, very little is known about the precise immune mechanisms involved in its use, or even if it is beneficial with various different routes of AAV administration,” said Editor-in-Chief Terence R. Flotte.

The research appears in Human Gene Therapy. (ANI)