Enterin has identified a family of aminosterol hormones originating in the dogfish shark, and a second family of aminosterols recently isolated from the brain and liver of a newborn mouse, which are profoundly neuroprotective. These compounds act on nerve cells both in the periphery and in the brain to prevent the unfolded protein response, enhance insulin sensitivity and repair dysfunctional neurons. As a class, these compounds potently inhibit regulatory phosphatases including PTP1B, the phosphatase intimately linked to the regulation of insulin and other growth factor signalling pathways.


Acting on enteric nerves, ENT-01 prevents alpha synuclein (αS) – the culprit in Parkinson’s Disease (PD) – from accumulating and aggregating within the enteric nervous system. Alpha synuclein, a defensive protein involved in the innate immune response, and induced in enteric nerves as a result of GI infections, accumulates in some individuals and eventually forms toxic aggregates which deposit on the inner nerve cell membrane. Membrane bound αS aggregates prevent enteric neurons from firing appropriately and cause constipation. More importantly, they impair neural signalling between gut and brain via the vagus nerve and as a result, neurologic symptoms develop.

Following oral administration, ENT-01, a positively charged molecule, enters enteric nerve cells and electrostatically displaces existing αS aggregates bound to the inner membrane. ENT-01 also prevents new αS aggregates from forming. αS is an intraneuronal protein and only a small fraction is secreted outside the nerve cell. Enterin is the only company targeting intraneuronal αS; other companies are attempting to trap αS outside nerve cells.

We have conducted three studies involving patients with Parkinson’s Disease. The first study, completed and published in 2019, involved 50 patients treated with escalating doses of ENT-01 for 25 days. Bowel motility was used to determine the efficacious dose. We showed dose-dependent improvement in constipation, circadian rhythm and sleep, and significant improvement in hallucinations, dementia, depression, and motor symptoms. In early 2022, we completed a 150 patient, randomized, dose-stratified, placebo-controlled Phase 2b study in which dose was escalated until bowels normalized, and then fixed for the remainder of the 25-day treatment period. Top-line results were made available in early 2022. To read the entire press release (from January 27, 2022) related to top-line results, please visit our News section. A replay of the conference call, during which Dr. Denise Barbut, MD, FRCP, Co-Founder, President and CMO of Enterin, shared the results is also available.

Encouraged by the results of the studies to date, we plan to initiate other future studies, including a study for patients with Parkinson’s Disease and psychosis, a study for patients with Parkinson’s Disease and dementia, and we are evaluating a potential study for patients with autism. For the latest status of the ENT-01 development program, please review our pipeline page.


Our second compound, ENT-03, reverses central insulin resistance, the central pathology in conditions ranging from obesity to type 2 diabetes and to Alzheimer’s Disease. It has been shown to inhibit PTP1B by acting on the hypothalamus. As a result, in both lean and obese, diabetic mice, it increases insulin sensitivity, normalizes blood sugar, reverses other metabolic abnormalities associated with these conditions, including liver function test abnormalities. It reduces food intake and produces very significant dose-dependent weight loss over prolonged periods. In two models of Alzheimer’s Disease, ENT-03 normalized memory and behavior, eliminated hypothalamic inflammation and prolonged life by over 50%. It is being developed for the treatment of type 2 diabetes, obesity and Alzheimer’s Disease. First-in-human studies will begin in 2023. For the latest status of the ENT-03 development program, please review our pipeline page.