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Prednisone may improve effectiveness of AAV-based gene therapy by reducing immune response

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Credit: Mary Ann Liebert, Inc., publishers

New Rochelle, NY, June 9, 2017–A new 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 published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Human Gene Therapy website until July 9, 2017.

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.

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Research reported in this publication was supported by the National Institutes of Health under 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.

About the Journal

Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies, is an authoritative peer-reviewed journal published monthly in print and online. Led by 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, Human Gene Therapy presents reports on the transfer and expression of genes in mammals, including humans. Related topics include improvements in vector development, delivery systems, and animal models, particularly in the areas of cancer, heart disease, viral disease, genetic disease, and neurological disease, as well as ethical, legal, and regulatory issues related to the gene transfer in humans. Its companion journals, Human Gene Therapy Methods, published bimonthly, focuses on the application of gene therapy to product testing and development, and Human Gene Therapy Clinical Development, published quarterly, features data relevant to the regulatory review and commercial development of cell and gene therapy products. Tables of contents for all three publications and a free sample issue may be viewed on the Human Gene Therapy website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Nucleic Acid Therapeutics, Tissue Engineering, Stem Cells and Development, and Cellular Reprogramming. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

Mary Ann Liebert, Inc. 140 Huguenot St., New Rochelle, NY 10801-5215 http://www.liebertpub.com Phone: (914) 740-2100 (800) M-LIEBERT Fax: (914) 740-2101

Media Contact

Kathryn Ryan
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Original Source

http://www.liebertpub.com/global/pressrelease/prednisone-may-improve-effectiveness-of-aav-based-gene-therapy-by-reducing-immune-response/2187/ http://dx.doi.org/10.1089/hum.2016.113

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