GenStar Reports Significant Advance in Gene Therapy For Chronic Diseases
BUSINESS WIRE - June 01, 2001 08:07SEATTLE, Jun 1, 2001 (BW HealthWire) -- Preclinical Data Supporting Immune Response Suppression in Hemophilia A To Be Presented at the Fourth Annual Meeting of the American Society of Gene Therapy GenStar Therapeutics (AMEX: GNT) today announced promising pre-clinical data regarding an advance in the ability of the Company's proprietary gene delivery system, Maximum Adenovirus (MAX-AD), to treat chronic disorders. The administration of the Company's MAX-AD Factor VIII treatment for hemophilia A, in conjunction with mild immune suppressors, resulted in significantly increased and sustained therapeutic levels of Factor VIII protein for the treatment of hemophilia A. The data were presented at the Fourth Annual Meeting of the American Society of Gene Therapy. "The ability to re-administer the MAX-AD Factor VIII without incurring a significant immune response is an important advance in gene therapy because of the promise it holds for treating chronic disorders," said Robert E. Sobol, M.D., Chief Executive Officer of GenStar. "We are further encouraged because the increased levels of Factor VIII observed after repeated administration improved the effectiveness of the treatment for hemophilia A." The pre-clinical study was designed to measure levels of the Factor VIII protein, a critical component to blood clotting, and the immune response to the therapy. The study showed that in mice, a dosing regimen of GenStar's gene therapy product, MAX-AD Factor VIII, with either a single or double dose of anti-CD4 antibodies (immune suppressing factors), resulted in a doubling of Factor VIII protein levels, from the first treatment (week 1) to the second treatment (week 17) for both the single and double dose. These levels were sustained with the third treatment (week 57) for the double dose. When studying the immune response to the MAX-AD vector, data showed that pre-treatment of mouse models with anti-CD4 antibodies followed by MAX-AD Factor VIII resulted in an immune response that was 100-fold less compared to mice that received the MAX-AD Factor VIII without anti-CD4 antibodies. A first generation adenoviral vector was studied in parallel and, despite pre-treatment with anti-CD4 antibodies, induced immune responses were 40 times greater than those of the MAX-AD Factor VIII treated group. "The type of results from studies such as these and those generated from earlier safety studies have been important in our discussions with the Internal Review Boards at clinical sites as we begin Phase I human clinical trials with MAX-AD FACTOR VIII for the treatment of hemophilia A," said Dr. Sobol. "We believe the high levels of Factor VIII correlate directly with the design of the MAX-AD vector system which was developed to maximize delivery capacity and minimize toxicities. Moreover, the findings support the broad use of our MAX-AD vector for the treatment of a wide variety of other disorders." Hemophilia A is a potentially life threatening hereditary disease that affects over 50,000 people in the United States and Europe. The disease results from a defect in the Factor VIII gene, which produces the Factor VIII protein essential for blood clotting. Current therapies for hemophilia A are based upon intermittent injections of the Factor VIII protein that do not provide the sustained levels of Factor VIII needed to prevent bleeding episodes characteristic of the disorder. GenStar's product carries the entire human Factor VIII gene sequence and uses a promoter gene designed for increasing Factor VIII expression in the liver, one of its normal biological sites of production. GenStar's MAX-AD Factor VIII gene therapy product for hemophilia A is a gene delivery system derived from the adenovirus, the common cold virus. In contrast to earlier gene delivery approaches, GenStar's delivery system has been engineered to remove all the viral genes providing a large DNA-delivery capacity for therapeutic genes that are responsible for the production of Factor VIII. MAX-AD has nearly 10 times the capacity of earlier generation vectors. |
