Oculo-pharyngo-distal myopathy, with or without leukoencephalopathy, is caused in particular by the repetition of the GGC triplet in regions of DNA previously considered non-coding within at least six genes (LOC642361, LRP12, GIPC1, NOTCH2NLC, RILPL1 and ABCD3). Researchers from France, China and Japan have shown that these sequences are in fact located within previously unknown open reading frames.
- This leads to the production of proteins containing polyglycine (more than 50 repeats).
- Antibodies developed against these proteins stain the p62-positive inclusions characteristic of these diseases.
- These proteins are capable of aggregating within muscle cells to form these inclusions and causing cell death.
- According to experiments in cell models and in mice, polyglycine-containing proteins cause muscle fibre atrophy associated with neurodegeneration and neuroinflammation.
- The cationic porphyrin TMPyP4 has been identified as a potential therapeutic avenue.
