research: doxycycline and muscular dystrophy

5 October 2005

The antibiotic doxycycline could delay the onset of oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy is an inherited disease that occurs mainly among French-Canadians who are descended from two French immigrants, a husband and wife who emigrated to Canada in 1634. It usually affects people around the age of 50, causing difficulties in swallowing and a progressive weakness of the eyelids and limbs. Although it does not affect life expectancy, there is no known cure.

The disease is caused by an abnormal expansion of a GCG trinucleotide repeat in a gene known as PABPN1 (poly(A)-binding protein nuclear 1). Instead of a stretch of ten alanines in a row, mutant proteins have 12–17 alanines and aggregate in the nuclei of skeletal muscle cells.

Using a transgenic mouse model that produces the mutant protein in its muscles, David Rubinsztein and colleagues in Cambridge found that doxycycline, a tetracycline antibiotic, could delay the onset of muscle weakness. The aggregation and toxicity of the mutant PABPN1 protein in cell nuclei were reduced, and the cells were less susceptible to cell death.

Dr Rubinsztein and colleagues suggest that as oculopharyngeal muscular dystrophy usually arises in late middle age, it may be possible to effectively cure such a disease if a way could be identified to delay the onset beyond normal life expectancy.

Davies JE et al. Doxycycline attenuates and delays toxicity of the oculopharyngeal muscular dystrophy mutation in transgenic mice. Nat Med 2005;11:672–7.