Safety and Potential Efficacy of Gene Therapy to Treat Genetic Disorder in Humans is Described in Human Gene Therapy.

NEW ROCHELLE, N.Y. -- Promising early-stage results of a gene therapy trial to replace Alpha-1 Antitrypsin (AAT) offer hope for the estimated 100,000 Americans with this life-threatening genetic form of emphysema, according to a paper published online ahead of print in the December 2006 issue (Volume 17, Number 12) of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc. The paper is available free online at www.liebertpub.com/hum.

AAT deficiency is one of the three most prevalent fatal genetic disorders. The other two are cystic fibrosis and Down's syndrome. The goal of gene therapy, or gene replacement, is to enable affected individuals to produce the alpha1 antitrypsin protein, eliminating the need for costly and difficult protein replacement therapy that requires weekly intravenous injections.

Studies in animals have suggested that periodic intramuscular injections of the AAT gene packaged in a viral delivery vector could result in safe, long-lasting production of recombinant AAT protein at therapeutic levels.

In this Phase I trial of AAT gene therapy, Brantly, Flotte and colleagues at the University of Florida, Gainesville, injected increasing doses of recombinant adeno-associated virus serotype 2 (rAAV2)-AAT vector into 12 AAT-deficient adults. All subjects discontinued AAT protein replacement therapy 28 days before receiving gene therapy.

The authors reported no serious adverse effects related to the gene therapy vector, supporting its safety. They were able to detect viral DNA sequences in the patients' blood, as well as antibodies to the viral vector. No other immune response to the recombinant vector was observed.

In the paper entitled, "Phase I Trial of Intramuscular Injection of a Recombinant Adeno-associated Virus Serotype 2 (rAAV2) Alpha-1 Antitrypsin (AAT) Vector in AAT-deficient Adults," Brantly et al report detecting low levels of AAT protein in the blood of one patient who had not been on AAT replacement therapy before the trial. Residual levels of previously injected AAT would likely have masked the presence of gene therapy-generated protein in other study subjects.

"This study represents an important first step in establishing the safety of gene replacement therapy for an important genetic disease. Expression of recombinant protein was low although there are a number of strategies that can be pursued to improve upon it in subsequent studies," says James M. Wilson, M.D., Ph.D., Editor-in-Chief, and Head of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, in Philadelphia.

Human Gene Therapy is an authoritative peer-reviewed journal published monthly in print and online that 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. Tables of contents and a free sample issue may be viewed online at www.liebertpub.com.

Mary Ann Liebert, Inc., 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 Tissue Engineering, Stem Cells and Development, and Cloning and Stem Cells. Its biotechnology trade magazine, Genetic Engineering 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 60 journals, books, and newsmagazines is available at www.liebertpub.com.

Mary Ann Liebert, Inc. 140 Huguenot St., New Rochelle, NY 10801-5215 www.liebertpub.com

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