HDAC6 histone deacetylase regulates a collection of mechanisms that allow the cell to protect itself in the case of protein aggregate accumulation (via chaperone proteins, microtubules, etc.). Its inhibition is being studied in several neurodegenerative pathologies (Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, etc.).
Up to now, this approach has only been studied in axonal forms of Charcot-Marie-Tooth disease. Korean researchers have evaluated CKD-504, an HDAC 6 inhibitor, in the most common form of demyelinating CMT, CMT 1A, associated with gene PMP22. Their results show that:
- when administered to CMT 1A mice modeling, CKD-504 improves myelination of the sciatic nerve, which improves motor skills in mice;
- in vitro studies using cells taken from patients with CMT 1A confirm that the product decreases the amount of PMP22 in Schwann cells.
The first toxicological studies are positive and a trial in healthy volunteers is currently underway in Huntington’s disease.