Oryzon picks HDAC6 inhibitor to develop as potential CMT treatment

ORY-4001 now to enter testing for possible Investigational New Drug application

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by Andrea Lobo |

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Oryzon Genomics has chosen ORY-4001, a selective histone deacetylase 6 (HDAC6) inhibitor, for clinical development as a potential treatment for Charcot-Marie-Tooth (CMT) disease and other neurological conditions.

HDAC6 enzyme inhibitors have shown promise for CMT, amyotrophic lateral sclerosis, and other neurological diseases, Oryzon states.

ORY-4001 will now enter studies to help support an Investigational New Drug application to conduct clinical trials.

“The nomination of ORY-4001 as a new candidate for clinical development is a clear confirmation of the excellence of the Epigenetic Discovery Programs at Oryzon,” Jordi Xaus, PhD, chief scientific officer at Oryzon, said in a company press release.

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CMT is a group of neurological conditions of the peripheral nerves, which control movement and sensation in the limbs.

The disease may lead to degeneration of nerve fibers and/or the myelin sheath — an insulating fatty sheath that ensures efficient signal transmission. As such, the nerves progressively lose the ability to transmit nerve signals between the brain and the limbs.

No effective treatments are currently available for CMT, a condition that affects 150,000 Americans and more than 3 million people worldwide, Oryzon states.

Deacetylases, such as HDAC6, are a class of proteins that modulate other proteins’ functions by removing a chemical motif, called an acetyl group. HDAC6, in particular, has been shown to be involved in the response to cellular stress and inflammation.

Blocking HDAC6 could restore myelin sheath in preclinical models of CMT1A

Previous studies showed that blocking HDAC6 could restore the myelin sheath in cell and mouse models of CMT type 1A, the most common type of CMT. It was also shown to be a potential therapeutic target for CMT type 2.

In 2022, Oryzon reached an agreement with the CMT Research Foundation to explore the company’s HDAC6 inhibitors. Selecting ORY-4001 as candidate for clinical development was based on positive preclinical results obtained under this collaboration.

According to the company, ORY-4001 has excellent pharmacology and exhibited very high selectivity against other HDAC types, with a safety profile that avoids toxicity to the blood. The compound also exhibited anti-inflammatory properties in animal models and positive effects in a CMT1A model.

Oryzon develops therapies for neurological disorders based on epigenetics, which refers to changes in how genes work that do not alter the DNA sequence itself.