A promising approach to gene therapy for hemophilia has beenreported by researchers at the University of Michigan medicalschool.
The scientists, writing this week in the Proceedings of theNational Academy of Sciences, have transformed capillarycells from rats with the human gene for Factor IX, the proteinmissing in hemophilia B.
The researchers used a mouse retrovirus to ferry the humanFactor IX gene into the rat capillary cells.
Hemophilia B, inherited from the mother, appears in about onein 30,000 people. It is caused by a defect in the gene encodingblood Factor IX, a crucial regulator of blood clotting.Hemophilia A, the more common form of the sex-linkeddisease, is caused by a deficiency in blood Factor VIII.
Other cell types, including skin and liver cells, have beentested as targets for gene therapy. But the researchers arguedthat capillary endothelial cells, with their intimate contactwith blood and their role in modulating blood composition andin regulating blood vessel function, are a superior candidate.Moreover, they noted, skin cells have not been able to transportthe recombinant protein into the bloodstream efficiently.
Treatment now involves supplying patients with factorspurified from human blood at a cost of about $50,000 per year.The therapy puts patients at risk for infection with theviruses that cause AIDS and hepatitis. Preparations ofrecombinant Factor IX would be safer, the researchers wrote.
Factor IX is in the research and development stage atcompanies such as Genetics Institute Inc. of Cambridge, Mass.;Rorer Biotech Inc. of King of Prussia, Pa.; Transgene SA ofParis; and ZymoGenetics Inc. of Seattle. Recombinant FactorVIII for hemophilia A is being developed by Cutter Labs, whichlicensed GenentechLs technology; Chiron Corp.; and BaxterHelathcare, which licensed GILs clone.Somatix Therapy Corp. ofAlameda, Calif., is pursuing gene therapy for hemophilia A.Targeted Genetics, an Immunex Corp. subsidiary, is alsointerested in pursuing gene therapy for type A as well as typeB, although it is not top priority, the company said.
Last summer, researchers at the Salk Institute in La Jolla,Calif., and the University of North Carolina, Chapel Hill,reported that they isolated skin fibroblasts from dogs withhemophilia B, introduced the canine Factor IX gene into them,grew the cells and transferred them back into the dogs.
The blood of dogs receiving the gene therapy clotted morerapidly than blood from an untreated animal, but the effectonly lasted one to two weeks.
-- Roberta Friedman, Ph.D. Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.