Public Release: 

Avigen Demonstrates Gene Therapy Success In Treating Animal Model Of Parkinson's Disease

Kureczka/Martin Associates

ALAMEDA, CA (October 27, 1997): Avigen (Nasdaq: AVGN) scientists and their collaborators announced the successful application of their adeno-associated virus (AAV) vector approach to gene therapy for use in the treatment of Parkinson's disease in an animal model of that illness. The scientists demonstrated the use of AAV vectors to deliver genes encoding two enzymes involved in dopamine production into the brains of rats with an induced form of Parkinson's disease. Abnormal rotational movement decreased significantly in parkinsonian rats receiving one or both genes, with those animals receiving both genes showing greater improvement over rats receiving only one of the genes.

The new research was presented October 26 by Avigen scientists and the company's collaborators at Jichi Medical School and Fujita Health University at the 27th Annual Society for Neuroscience Meeting in New Orleans, Louisiana.

Parkinson's disease is a progressive, degenerative disorder characterized by tremor and rigidity, and often, slowed and abnormal movement. An estimated 500,000 Americans suffer from the disease. The symptoms result from the progressive loss of brain cells that produce a neurotransmitter called dopamine which is released in an area of the brain called the striatum; the severity of Parkinson's disease in an affected individual is proportional to the decline in the amount of dopamine in their striatum.

The brain normally produces dopamine from a precursor, the amino acid called tyrosine, which is a component of foods. This conversion process has two steps. Tyrosine is first converted to a molecule called L-dopa by an enzyme in the brain called tyrosine hydroxylase (TH); L-dopa is subsequently converted into dopamine by a second brain enzyme called L-amino acid decarboxylase (AADC). Patients with Parkinsons' disease can initially be treated by orally administering the intermediate, L-dopa. This treatment, however, usually becomes less effective with the progression of disease and must often be discontinued due to numerous serious side-effects produced by the increasing doses of drug that must be administered to achieve a therapeutic effect. A more recent experimental approach has been to locally produce dopamine in the striatum by grafting fetal midbrain cells into the patient's brain. There are serious practical and ethical issues associated with this approach. Using gene th! ! erapy to restore the brain's capacity to produce dopamine offers a novel potential alternative for the treatment of Parkinson's disease.

Avigen scientists and their collaborators first showed, using a marker gene, that delivery of AAV vectors containing that gene into the striatum of rats resulted in gene expression for several months with no pathological changes in the brains of the animals. The researchers then produced two AAV vectors, one containing the TH gene (AAV-TH) and the other containing the AADC gene (AAV-AADC), and delivered these vectors directly into the striatum of rats having a laboratory-induced form of Parkinson's disease. Abnormal movement decreased significantly in animals receiving AAV-TH alone or a combination of AAV-TH and AAV-AADC; animals receiving both vectors showed better recovery than animals receiving AAV-TH alone.

"This study demonstrates the ability of AAV vectors to efficiently transfer one or more genes to localized regions of the brain, and once there, to achieve long-term production of a therapeutic protein," said Gary Kurtzman, M.D., Avigen vice president of research and development. "Our findings offer a novel approach to the treatment of Parkinson's disease, and we are evaluating the delivery of additional genes to the brain that might further increase the therapeutic effect observed in this study."

"Parkinson's disease is a particularly attractive target for gene therapy because, unlike many neurological disorders, the particular defect underlying the disease and area of the brain affected is well understood," said John Monahan, Ph.D., president and chief executive officer of Avigen. "We are very encouraged by our research results to date and are looking to work with additional collaborators and a corporate partner to bring this therapeutic approach to the clinic."

Avigen, Inc. is a biotechnology company involved in the development of gene therapy products derived from adeno-associated virus for the treatment of inherited and acquired diseases. The Company's proposed gene therapy products are designed for in vivo administration to achieve the production of therapeutic proteins within the body. Avigen is focusing its efforts on developing products to deliver genes for the treatment of hemophilia, brain cancer, hyperlipidemia, metabolic storage diseases and blood cell-related diseases including sickle cell anemia, beta-thalassemia and HIV.

Except for the historical inforrmation contained herein, this news release contains forward-looking statements that involve risks and uncertainties, including the Company's preclinical and clinical efforts, the anticipated timing of regulatory filings and approvals, and other risks detailed from time to time in documents filed by Avigen with the SEC, including the report on Form 10-K for the year ended June 30, 1997 and the report on Form 10-Q for the quarterly period ended March 31, 1997 Source Avigen, Inc.

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