Jan 23, 2018 | Updated: 09:54 AM EDT

Long-term treatment success using gene therapy to correct a lethal metabolic disorder

Oct 10, 2014 12:17 AM EDT

Excessive and often lethal blood levels of bilirubin can result from mutations in a single gene that are the cause of the metabolic disease known as Crigler-Najjar syndrome type 1 (CNS1). A new gene therapy approach to correcting this metabolic error achieved significant, long-lasting reductions in bilirubin levels in a mouse model of CNS1 and is described in an Open Access article in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available on the Human Gene Therapy website at http://online.liebertpub.com/doi/full/10.1089/hum.2013.233.

In "Life-Long Correction of Hyperbilirubinemia with a Neonatal Liver-Specific AAV-Mediated Gene Transfer in a Lethal Mouse Model of Crigler-Najjar Syndrome," Giulia Bortolussi and coauthors from the International Centre for Genetic Engineering and Biotechnology; Centro Studi Fegato, Fondazione Italiana Fegato; and University of Trieste (Trieste, Italy) and Charles University (Prague, Czech Republic), present details of the adeno-associated virus (AAV)-mediated gene therapy approach they used to correct the metabolic disorder that causes hyperbilirubinemia in CNS1. The researchers reported 70-80% reductions in plasma bilirubin levels early on among treated animals, with about 50% reductions maintained throughout the study. The authors compared the effectiveness of two delivery strategies: targeting the therapeutic gene directly to the liver or, preferably, to skeletal muscle. They discuss the implications of the different results they obtained with each approach.

"CNS1 is an outstanding model for in vivo gene therapy with easily measured and clinically relevant metabolic endpoints," says James M. Wilson, MD, PhD, Editor-in-Chief ofHuman Gene Therapy, and Director of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia.

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. Human Gene Therapypresents 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 sister 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 and sample issues for all three publications may be viewed on the Human Gene Therapy website at http://www.liebertpub.com/hgt.

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 areas of science and biomedical research, including Nucleic Acid Therapeutics, Tissue Engineering, Stem Cells and Development, and Cellular Reprogramming. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), 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 athttp://www.liebertpub.com.

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