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Monday, July 17, 2017

Backers put $12.7M behind Enterin's Parkinson's disease approach

July 17, 2017  by  Phil Taylor  

Philadelphia biotech Enterin has raised $12.7 million in funding to pursue its hypothesis that Parkinson's disease originates in the gut, not the brain.

The first-round financing is backed by new investor New Ventures III and will help Enterin complete an ongoing phase 1/2 trial of its lead drug ENT-01—which targets a substance call alpha-synuclein that it believes has a key role to play in the development of Parkinson's.

It's been well demonstrated that alpha-synuclein—a protein which is normally found in the nervous system but whose function isn't well understood—builds up and clogs neurons in brains of patients who develop Parkinson's.

A mis-folded form of protein that affects the release of seems to be the root cause of the trouble, preventing the release of the neurotransmitter dopamine from nerve junctions and damaging neurons, and a number of research groups including biotech Prothena have been looking at targeting alpha-synuclein with new therapies.

Enterin's spin on the alpha-synuclein hypothesis is that the protein starts accumulating in nerves within the intestines of Parkinson's patients, causing symptoms such as constipation long before the central nervous system effects become apparent.

From the nerves in the gut—known as the enteric nervous system—the disruptive protein spreads to the brain stem and eventually into the areas that control mobility and muscle control, according to Enterin.

ENT-01, an oral drug that contains a synthetic derivative of squalamine called kenterin, is designed to displace alpha-synuclein from nerve cells within the enteric nervous system and Enterin's clinical trial is testing whether it can relieve constipation associated with Parkinson's.

Constipation serves as a surrogate marker for the possible benefits on the central nervous system symptoms of the disease, but is also a significant clinical problem for Parkinson's patients in its own right, causing problems in around two thirds of them.

The company also hopes that other symptoms of Parkinson's could be improved ENT-01, according to chief medical officer Denise Barbut, M.D.

"While the study is focused on functional improvement of the enteric nervous system, we are closely monitoring central nervous system symptoms such as sleep, REM-behavior disorder, depression, fatigue and even motor symptoms," she said.

Research recently published by Enterin's co-founder Michael Zasloff M.D. Ph. D., of Georgetown University and collaborators demonstrated that squalamine both reduced the formation of toxic alpha synuclein clumps and their toxicity in animal models of Parkinson's disease.

He said the new financing "will enable us to complete the ongoing phase 2 study … further expand our understanding of the role of alpha-synuclein in the pathology of Parkinson's disease and begin to explore other indications."

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