The term “epigenetic” refers to the control or modification of gene expression via processes that do not alter the underlying gene sequence. Such activity is typically orchestrated by chemical modifications to a cell’s DNA or to DNA-related structural proteins called histones, or by non-coding RNAs (ncRNA).
Epigenetic mechanisms play a crucial role in regulating many important cellular functions, from simple protein synthesis to large-scale phenotypic shifts such as cell differentiation. Substances such as larsucosterol (DUR‑928) that can epigenetically influence gene expression may hold substantial therapeutic promise and are the basis of active drug development at DURECT.
DURECT's Epigenetic Regulator program is a collaborative effort between DURECT and the Department of Internal Medicine at Virginia Commonwealth University (VCU), the VCU Medical Center and the McGuire VA Medical Center. The program capitalizes on more than 20 years of research by Shunlin Ren, M.D., Ph.D., Professor of Internal Medicine at the VCU Medical Center.
The program builds on the recent discovery of a family of endogenous small molecules that may have therapeutic utility in a wide range of diseases and syndromes—both orphan in nature and affecting broader patient populations. Larsucosterol, the lead compound in this program, appears to be highly conserved across species. Nonclinical studies have shown it to epigenetically modulate the activity of multiple nuclear receptors and to play a key regulatory role in cell functions, including lipid homeostasis, inflammation, and cell survival.
Larsucosterol is an investigational product and has not been approved by the FDA for marketing in the U.S. for any indication.