Oculopharyngodistal myopathy: toxic proteins identified
The discovery that the abnormal repetition of a short DNA sequence leads to the production of toxic proteins opens the way to new therapeutic approaches in oculopharyngodistal myopathy and oculopharyngeal myopathy with leukoencephalopathy.
Oculopharyngodistal myopathy is a rare genetic disease caused by the repetition of a short three-nucleotide motif in DNA. In particular, the GGC sequence can be repeated in at least six genes involved in these diseases, within regions of DNA that normally do not code for proteins (non-coding sequences).
Researchers from France, China and Japan showed that these repeat expansions lead to the production of previously unknown toxic proteins composed of long chains of glycine. Without GGC repeat expansion, these sequences remain “invisible” because they are too short to be translated into proteins.
These proteins form aggregates in muscle cells that can trigger cell death and are characteristic of oculopharyngodistal myopathy.
A first step towards therapeutic approaches
Experiments conducted in cellular and mouse models highlighted the toxicity of polyglycine-containing proteins in muscle and the central nervous system: they cause muscle fibre atrophy associated with neurodegeneration and neuroinflammation.
Among the various compounds tested by the researchers, the cationic porphyrin TMPyP4 was identified as a potential therapeutic approach capable of preventing aggregation and toxicity of polyglycine-containing proteins.
Source
GGC repeat expansions within new open reading frames are translated into toxic polyglycine proteins in oculopharyngodistal myopathy
Boivin M, Yu J, Eura N et al.
Nat Genet. 2026 Mar.