Scientists at the University of Wisconsin and in England haveused gene therapy to repair the genetic defect of Duchenne'smuscular dystrophy on a very limited basis in mice.
The researchers injected a gene construct for the defect, themissing protein dystrophin, into the muscles of the mice. Themice then expressed the human dystrophin protein.
However, both the researchers involved and the company thatinvented the technology caution that a much larger number ofmuscle fibers will have to be repaired for the strategy to worktherapeutically.
An analysis accompanying the report today in Nature alsoemphasized that only 1 percent of muscle fibers was convertedby the injection to express dystrophin. "The overallinefficiency is breathtaking," commented Terence A. Partridge,a histopathologist at Charing Cross and Westminster MedicalSchool in London.
In fact, Vical Inc. has put the muscular dystrophy approach onhold while pursuing a more general application of its genetransfer technology.
The privately held San Diego company has signed a licensingagreement with Merck & Co. Inc. to use the technology invaccines. The company intends to develop its approach as ageneral strategy to deliver purified genes as drugs, withoutviral vectors and with the ability to start and stop therapy asneeded.
In contrast, other gene therapies envision a one-shottreatment that permanently inserts a desired gene into apatient's cells to repair genetic defects.
Earlier work by Vical's Philip Felgner in collaboration with JonWolff at the University of Wisconsin in Madison showed that areporter gene could be planted in rodent muscle cells andwould function for up to a year.
In this week's report, Wolff's lab and collaborators at Guy'sHospital in London and John Radcliffe Hospital in Oxfordinjected a full-length cDNA of human dystrophin into themuscles of dystrophin-deficient mice. Most of the muscle cellsthat expressed the human dystrophin were within 5millimeters of the injection site, the area in which theinjection fluid dispersed.
Vical and the University of Wisconsin hold a joint patent, withVical owning exclusive rights to the transfer technology. --Roberta Friedman, Ph.D.
(c) 1997 American Health Consultants. All rights reserved.