Inflammatory factors linked to inhibition of factor VIII gene therapy in hemophilia A

December 07, 2017

New Rochelle, NY, December 7, 2017--As a gene therapy cure for hemophilia A moves closer to reality, a new study sheds light on a challenging complication in which a host autoimmune response inhibits the production of normal clotting factor VIII from the transferred FVIII gene. Researchers compared the levels of multiple pro- and anti-inflammatory cytokines in a mouse model of hemophilia A that received FVIII gene therapy at different ages and either did or did not exhibit FVIII inhibitor formation, as presented in an article 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 January 7, 2017.

The article entitled "A Retrospective Study of Cytokine Profiles Changes in Mice with FVIII Inhibitor Development after Adeno-Associated Virus-Mediated Gene Therapy in a Hemophilia A Mouse Model" is coauthored by Junjiang Sun, Gene Therapy Center and Eshelman School of Pharmacy, University of North Carolina (UNC, Chapel Hill), and colleagues from UNC, University of Saint Joseph School of Pharmacy (Hartford, CT), Northern Jiangsu People's Hospital (Yangzhou, China), Chinese Academy of Medical Sciences, and Peking Union Medical College (Beijing, China). The researchers reported a shift in the cytokine profiles of mice with FVIII inhibitor development, including significantly increased levels of pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 and tumor necrosis factor (TNF)-alpha, among others. They also showed a negative correlation between risk factors for FVIII inhibitor development and age at which gene therapy was administered.

"Immune responses represent an important limitation to gene therapy for hemophilia," 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. "The paper from Dr. Sun's group and their colleagues begins to address factors that may predispose certain individuals to mount a greater immune response against the therapeutic protein produced by the gene therapy vectors and thus benefit less from the therapy."
-end-
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 and focused 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 Therapywebsite.

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 http://www.liebertpub.com/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

Mary Ann Liebert, Inc./Genetic Engineering News

Related Gene Therapy Articles from Brightsurf:

Risk of AAV mobilization in gene therapy
New data highlight safety concerns for the replication of recombinant adeno-associated viral (rAAV) vectors commonly used in gene therapy.

Discovery challenges the foundations of gene therapy
An article published today in Science Translational Medicine by scientists from Children's Medical Research Institute has challenged one of the foundations of the gene therapy field and will help to improve strategies for treating serious genetic disorders of the liver.

Gene therapy: Novel targets come into view
Retinitis pigmentosa is the most prevalent form of congenital blindness.

Gene therapy targets inner retina to combat blindness
Batten disease is a group of fatal, inherited lysosomal storage disorders that predominantly affect children.

New Human Gene Therapy editorial: Concern following gene therapy adverse events
Response to the recent report of the deaths of two children receiving high doses of a gene therapy vector (AAV8) in a Phase I trial for X-linked myotubular myopathy (MTM).

Restoring vision by gene therapy
Latest scientific findings give hope for people with incurable retinal degeneration.

Gene therapy/gene editing combo could offer hope for some genetic disorders
A hybrid approach that combines elements of gene therapy with gene editing converted an experimental model of a rare genetic disease into a milder form, significantly enhancing survival, shows a multi-institutional study led by the University of Pennsylvania and Children's National Hospital in Washington, D.C.

New technology allows control of gene therapy doses
Scientists at Scripps Research in Jupiter have developed a special molecular switch that could be embedded into gene therapies to allow doctors to control dosing.

Gene therapy: Development of new DNA transporters
Scientists at the Institute of Pharmacy at Martin Luther University Halle-Wittenberg (MLU) have developed new delivery vehicles for future gene therapies.

Gene therapy promotes nerve regeneration
Researchers from the Netherlands Institute for Neuroscience and the Leiden University Medical Center have shown that treatment using gene therapy leads to a faster recovery after nerve damage.

Read More: Gene Therapy News and Gene Therapy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.