Cyclosporine-Like Compound
Prevents Cell Death In CMD Mice

Abnormalities in mitochondria, the energy-producing units inside cells, appear to underlie the muscle degeneration seen in Ullrich congenital muscular dystrophy (CMD), a form of MD caused by a lack of the protein known as collagen 6.

Scientists at the University of Padua and other Italian institutions, who published their results in the Jan. 16 issue of Proceedings of the National Academy of Sciences, found that mutant mice unable to produce collagen 6 show mitochondrial defects that lead to cell death. Specifically, a channel in the inner membrane surrounding each mitochondrion opens inappropriately, triggering a cell suicide program.

When the researchers next studied muscle cells from five patients with Ullrich CMD, they found similar defects in their mitochondria, with similar results.

The muscle cell defects were reversed when the drug cyclosporine, which keeps the mitochondrial channel closed, was added to their environment, leading the investigators to think about this as a potential therapy for Ullrich CMD.

However, since cyclosporine is also a potent immune system suppressant, they decided to try the efficacy of a related compound, Debio 025. This compound, like cyclosporine, stabilizes mitochondria by keeping their inner membranes intact, but it doesn’t have immunosuppressive effects.

Debio 025 was shown to be equally effective in preventing mitochondrial defects and death of muscle cells from Ullrich CMD patients.

The researchers say their findings suggest new perspectives for treatment of patients with collagen 6 disorders.