Gene therapy slows progression of fatal neurodegenerative disease in children

Gene therapy to replace the faulty CLN2 gene, which causes a neurodegenerative disease that is fatal by age 8-12 years, was able to slow significantly the rate of neurologic decline in treated children, according to a paper published online ahead of print in the May 2008 issue (Vol. 19 No. 5) of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc.

Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) is an autosomal recessive genetic disorder that causes degeneration of the central nervous system. It is a form of Batten disease, a group of lysosomal storage disease in which a lipofuscin-like material is not broken down and accumulates in neurons, causing cognitive impairment, visual failure, seizures, and progressive deterioration of motor function.

Ronald Crystal and colleagues from Weill Cornell Medical College (New York, NY), describe a study conducted in 10 children with LINCL who received gene therapy to replace the defective CLN2 gene via administration of human CLN2 carried in an adeno-associated virus (AAV). In the paper entitled “Treatment of Late Infantile Neuronal Ceroid Lipofuscinosis with CNS Administration of a Serotype 2 Adeno-associated virus expressing the CLN2 cDNA,” the authors report that over an 18-month period, assessment using a neurologic rating scale demonstrated significant slowing of disease progression in the treated, compared to the untreated children. On the basis of these findings, the authors proposed that additional studies to assess the safety and efficacy of AAV-mediated gene therapy for LINCL be pursued.

Although the treatment was associated with some serious adverse events in some patients, these were not unequivocally attributable to the gene therapy vector.

“This clinical trial is an important step toward the development of treatments for this group of underserved inherited neurodegenerative disorders,” says James M. Wilson, MD, PhD, Editor-in-Chief and Head of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, at the University of Pennsylvania School of Medicine, in Philadelphia.

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Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy and the British Society for 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.

Mary Ann Liebert, Inc. (liebertpub.com), 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 & 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 60 journals, books, and newsmagazines is available online.