A randomized, double-blind, placebo-controlled study of histone deacetylase type 6 inhibition for the treatment of painful diabetic peripheral neuropathy

David Michelson; William W Chin; Robert H Dworkin; Roy Freeman; David N Herrmann; Ralph Mazitschek; Rodica Pop-Busui; Aziz Shaibani; James Vornov; Melissa Jones; Matthew Jarpe; Brittany Hader; Theresa Viera; Michelle Hylan; Tim Kachmar; Simon Jones

doi:10.1097/PR9.0000000000001114

A randomized, double-blind, placebo-controlled study of histone deacetylase type 6 inhibition for the treatment of painful diabetic peripheral neuropathy

Pain Rep. 2023 Oct 26;8(6):e1114. doi: 10.1097/PR9.0000000000001114. eCollection 2023 Dec.

Authors

Affiliations

¹ Regenacy Pharmaceuticals, Inc, Waltham, MA, USA.
² University of Rochester, Rochester, NY, USA.
³ Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA.
⁴ Massachusetts General Hospital, Harvard University, Boston, MA, USA.
⁵ Department of Internal Medicine, Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA.
⁶ Baylor College of Medicine, Houston, TX, USA.
⁷ Medpace, Inc. and Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁸ Medpace, Inc, Cincinnati, OH, USA.

Abstract

Introduction: Current treatments for painful diabetic peripheral neuropathy (DPN) are insufficiently effective for many individuals and do not treat nonpain signs and symptoms. The enzyme histone deacetylase type 6 (HDAC6) may play a role in the pathophysiology of painful DPN, and inhibition of HDAC6 has been proposed as a potential treatment.

Objectives: To assess the efficacy and safety of the novel HDAC6 inhibitor ricolinostat for the treatment of painful diabetic peripheral neuropathy.

Methods: We conducted a 12-week randomized, double-blind, placebo-controlled phase 2 study of the efficacy of ricolinostat, a novel selective HDAC6 inhibitor, in 282 individuals with painful DPN. The primary outcome was the change in the patient-reported pain using a daily diary, and a key secondary outcome was severity of nonpain neuropathic signs using the Utah Early Neuropathy Scale (UENS) score.

Results: At the 12-week assessment, changes in average daily pain and UENS scores were not different between the ricolinostat and placebo groups.

Conclusion: These results do not support the use of the HDAC6 inhibitor ricolinostat as a treatment for neuropathic pain in DPN for periods up to 12 weeks.

Keywords: Histone deacetylase 6 inhibition; Painful diabetic peripheral neuropathy.