making muscle wasting history

During development, the protein biglycan is present at the outside of the skeletal and heart muscles and connects with its two ends the proteins alpha- and gamma-sarcoglycan, which are two components of the dystrophin-protein complex in the muscle cell membranes. Biglycan is important for the regulation of many signaling and structural proteins of the muscle membrane. Experiments done by Prof. Justin Fallon and his co-workers at Brown University in Providence, Rhode Island, with non-dystrophic mice, whose gene for biglycan had been deactivated, showed that in the absence of biglycan many proteins of the dystrophin complex had disappeared.

Treating these mice with local and systemic injections of recombinant (artificially made) human biglycan led to the re-appearance of the proteins beta-syntrophin and alpha-dystrobrevin, which was an indication that the dystrophin complex had been restored. The most surprising finding was that two to three weeks after systemic single injections of human biglycan into mdx mice, their normally low level of utrophin was upregulated about 2.5 fold.

After three months of repeated systemic injections, the muscles of these mice without dystrophin were much more resistant to damage caused by forced lengthening. As the two proteins to which biglycan binds, are only present in skeletal and cardiac muscles, biglycan could be active primarily in these two types of muscles, and thus may have minimal side effects. Immune reaction is not expected to be a problem because biglycan is present during development in humans. Since it acts outside the muscle cells, biglycan does not have to cross the muscle membranes when used as a therapeutic agent.

Experiments with animals will continue to optimize treatment conditions. And after sufficient human biglycan in clinical grade purity is available, a phase-I clinical trial could be started in about two years.