Silicon Investor (SI) -- The First Internet Community

STOCKTALK

We've detected that you're using an ad content blocking browser plug-in or feature. Ads provide a critical source of revenue to the continued operation of Silicon Investor. We ask that you disable ad blocking while on Silicon Investor in the best interests of our community. If you are not using an ad blocker but are still receiving this message, make sure your browser's tracking protection is set to the 'standard' level.

Biotech / Medical : Regeneron Pharmaceuticals -- Ignore unavailable to you. Want to Upgrade?

To: Miljenko Zuanic who wrote (566)	9/20/2001 8:14:29 PM
From: Miljenko Zuanic	Read Replies (1) \| Respond to of 3557

Mini-Protein Restores Muscle Function in Murine Model of Muscular Dystrophy -------------------------------------------------------------------------------- LONDON (Reuters Health) Sept 19 - By designing a "mini-gene" of the protein agrin, a multinational team of investigators has been able to restore muscle function in a mouse model of the most severe form of congenital muscular dystrophy. That form, merosin-deficient congenital muscular dystrophy, involves mutations in the laminin alpha-2 chain in muscle and peripheral nerve, the investigators note. Deficiency of laminin alpha-2 is accompanied by upregulation of other laminins that bind only weakly to alpha-dystroglycan, a protein in the plasma membrane of muscle fiber. Dr. Markus A. Ruegg and colleagues became interested in the protein agrin, which normally, according to Dr. Ruegg, "induces postsynaptic structures at the neuromuscular junction." "We found that agrin binds to alpha-dystroglycan and to the laminins," Dr. Ruegg, of the University of Basel in Switzerland, told Reuters Health. Based on that information, he and his colleagues developed a transgenic mouse that expressed a miniaturized agrin molecule that retained these functional binding sites. According to Dr. Ruegg, the team then bred these mice with mice carrying a mutation that causes congenital muscular dystrophy. The cross-bred mice were healthier than the mice with the muscular dystrophy mutation, as exemplified by weight gain, growth curves, tests of locomotion, and longevity. The mini-agrin protein was expressed at high levels in skeletal muscle, according to the team's report in the September 20th issue of Nature. These results are "a nice example of exploiting the functional properties of a protein to rescue a disease phenotype," Dr. Ruegg said. "What I think is most interesting is the possibility of applying this methodology to other molecules and to other diseases." Once appropriate vectors are developed, Dr. Ruegg believes, trials of gene therapy using mini-agrin may be appropriate for humans. "Mini-agrin would probably pose fewer problems than replacing the diseased laminin alpha-2 subunit gene itself with a new gene," he said. Such a gene product, previously unrecognized by the body, would probably cause a strong immune response, he explained. "In contrast, our engineered protein has an epitope expressed in other tissue, such as the kidney and the neuromuscular junction. So the body should not generate antibodies against the mini-agrin molecule." Nature 2001;413:302-307.