PROBLEM

Metabolic diseases and peripheral neuropathies represent a major public health burden in the United States, and the risks increase as we age. Metabolic diseases, including diabetes and obesity, and peripheral neuropathy (PN) affect approximately 25-45% and 10-20% of U.S. adults aged 50-70 respectively. PN often results in significant pain, disability, and reduced quality of life. Current treatments rely on lifestyle modification, glycemic control, reducing lipids, and symptomatic pain relief. These approaches often fail to halt disease progression or restore nerve function, underscoring a critical unmet need for effective interventions that improve outcomes beyond symptom management. There is currently no cure for PN.

SOLUTION

Estrogen receptor-beta (ERβ) has emerged as a promising therapeutic target for reducing tumor burden in cancer, and regulation of inflammation and fibrosis. Researchers at The Ohio State University recently demonstrated that non-feminizing 17-alpha-estradiol (17aE2) which is less estrogenic than the more common 17-beta-estradiol) is protective against age-related metabolic perturbations and peripheral nerve degeneration. In male and female mice, 17aE2 mitigates metabolic disease symptoms and peripheral neuropathy in male and female mice and was associated with increased lifespan in male mice. Like 17aE2, ERβ has fewer deleterious side effects and is non-carcinogenic and is a likely mechanistic target of 17aE2. OSU-ERβ-12 is a novel small molecule ERβ agonist developed at OSU and can be used to preserve nerve function and improve metabolic health, offering a promising therapy for neuropathy and metabolic disease, including with aging.

APPLICATIONS

• Treatment of metabolic disorders, including diabetes, adipose dysfunction, and obesity, with or without age-related etiology
• Treatment of peripheral neuropathy, such as small fiber neuropathy in tissues and organs, including aging

ADVANTAGES

• High efficacy and selectivity: OSU- ERβ -12 is a potent agonist and has >100-fold selectivity for ERβ over Erα, resulting in limited off-target effects
• Orally bioavailable at easily translatable doses (~10 mg/kg)
• Favorable pharmacokinetic properties: Previous studies with OSU- ERβ -12 in mice, research hounds, and mini pigs demonstrated an advantageous PK profile compared to clinically used ERβ agonists
• Dual benefit: OSU-ERβ-12-mediated ERβ activation can improve both peripheral nerve integrity and protect against metabolic dysfunction

Seeking opportunities for out-licensing, co-development, and collaboration