CMTRF supporting work needed to move HDAC6 inhibitor into trials
Augustine Therapeutics aiming for 'first truly curative option for CMT patients'
The CMT Research Foundation (CMTRF) is joining forces with Augustine Therapeutics to accelerate research into a small molecule therapy for Charcot-Marie-Tooth disease (CMT), with the goal of moving it into clinical testing.
With CMTRF and past financial support, Augustine will conduct further studies in its lead, third-generation HDAC6 inhibitor as a potential CMT treatment. Planned work in rodents includes the testing of dose ranges, treatment toxicology and safety, and long-term efficacy.
“This development progress will be greatly expedited thanks to the support provided by the CMT Research Foundation … as we move towards IND enabling studies,” Sylvain Celanire, CEO of Augustine, said in a CMTRF press release. Investigational New Drug (IND)-enabling studies are intended to support regulatory clearance to start a clinical trial.
Third-generation inhibitor showed potential in mouse CMT1A models
Deacetylation is a process that removes an acetyl group from a protein, changing its function. HDAC6 — short for histone deacetylase 6 — is an enzyme that modulates cellular activity via deacetylation.
Inhibitors of HDAC6 activity have shown therapeutic potential in different types of CMT. HDAC6 is a validated molecular target for neuropathies and neurodegenerative diseases, with a potential to treat other conditions, the company states on a webpage.
“Augustine aims to deliver the first truly curative option for CMT patients. Following promising preclinical studies, we are on the right track to advance our lead candidate toward future clinical tests,” said Ludo Van Den Bosch, PhD, founding scientist at Augustine and chairman of its scientific advisory board.
According to the Belgium-based company, a four-week study in a CMT1A mouse model showed that its lead HDAC6 inhibitor bound to the HDAC6 enzyme and halted disease progression over those weeks. The therapy also reversed several CMT-related complications in the mice, including biomarkers of nerve fiber (axonal) damage.
Augustine reported that its latest generation of HDAC6 inhibitors do not show the toxicity linked with earlier inhibitor versions. The planned studies will further insight into these inhibitors’ mode of action at the cellular level.
“HDAC6 inhibitors are promising as potential therapeutics for several forms of CMT,” said Cleary Simpson, CEO of the CMTRF. “We are hopeful that this collaboration will accelerate the progress of finding a cure for CMT1A patients who currently have no available treatment options.”
The amount of funding given by the CMT Research Foundation for the planned studies was not disclosed in the release.