Biglycan
Biglycan
Justin Fallon of Brown University in Providence RI described an unexpected discovery that could lead to a therapy for Duchenne Muscular Dystrophy. His laboratory has been working for the past eight years on the extracellular protein biglycan, BGN.
This until now rather unknown protein connects the two ends of the proteins alpha- and gamma-sarcoglycan of the complex on the outside of the membranes of skeletal muscles. In experiments with mice whose gene for BGN had been eliminated, it was found that the amount of many proteins of the dystrophin complex was reduced. Treating these mice with local and systemic injections of BGN led to the re-appearance of betasyntrophin, which was an indication that the dystrophin complex was restored. Biglycan seems to be particularly important in juvenile mice at a time when the muscle do not need dystrophin, but rather rely on utrophin. Very recent work presented at the meeting showed that biglycan can also be administered to mdx mice where it had positive effects on countering the dystrophic pathology of the muscle. Since BGN is normally present in low concentrations in mice, immunological reactions did not appear, and none would be expected in humans either. Alpha- and gamma-sarcoglycans are only present in skeletal and cardiac muscles. And because BGN binds to these two proteins, it could be active primarily in these two types of muscles, and thus may have minimal side effects. Experiments with animals will continue to optimize treatment conditions. Phase-I clinical trials could then be started in two years with this unexpected potential new Duchenne drug: biglycan.
From Günter Scheuerbrandt Report of the PPMD Conference 2006