8:45 AM
Feb 12, 2018
 |  BC Extra  |  Preclinical News

HDAC3 inhibition promotes peripheral remyelination

A study published in Nature Medicine identified histone deacetylase 3 (HDAC3) as a target for boosting remyelination in peripheral neuropathies.

Following demyelination in a mouse model of sciatic nerve injury, researchers from Cincinnati Children’s Hospital Medical Center and colleagues showed that tool compound HDAC3 inhibitors increased the number of myelin-producing Schwann cells at the injury site, as well as the number of myelinated axons and thickness of myelin sheaths, compared with vehicle. The compounds also increased action potential conduction and motor function in the mice.

While HDAC3 acts as a brake on Schwann cell development, the authors cited a study suggesting the epigenetic regulator appears to do the opposite in oligodendrocytes, the myelinating cells in the CNS. Lead author Richard Lu at Cincinnati Children's told BioCentury the team plans to test whether HDAC3 inhibition may be suitable for multiple sclerosis and other CNS demyelinating disorders.

BioMarin Pharmaceutical Inc. (NASDAQ:BMRN) is the only company with a disclosed HDAC3 inhibitor, according to BioCentury's BCIQ database. RG2833 has completed Phase I testing to treat Friedreich's ataxia (FRDA). BioMarin acquired the candidate from Repligen Corp. (NASDAQ:RGEN) in 2014.

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