Can Oral Prednisone Improve the Effectiveness of Gene Therapy?

Gene transfer using adeno-associated virus (AAV)-based gene delivery into the skeletal muscle of rhesus macaques showed that the oral prednisone reduced immune responses to AAV and could weaken the expression of the therapeutic transgene over time.

The animals when given prednisone before the gene therapy could have a 60% decrease in the immune cell that inflitrates, and is comprised of cytotoxic T cells, finds a new study published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert publishers.

‘Prednisone drug in conjunction with adeno-associated virus (AAV)-based gene delivery could help to blunt the harmful immune responses to the AAV capsid.’

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.

The researchers report their findings in the article entitled "Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone."

"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," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA.



Source: Eurekalert