PHILADELPHIA, Aug. 27, 2019 /PRNewswire/ -- Enterin Inc., a privately held, CNS-focused pharmaceutical company based in Philadelphia developing novel compounds to treat neurodegenerative diseases, announces the publication of its Phase 2a RASMET study. The article entitled "Targeting neurons in the gastrointestinal tract to treat Parkinson's Disease" was published online in Clinical Parkinsonism and Related Disorders.
RASMET was a Phase 2a multicenter, dose-escalating study to evaluate the safety, tolerability and efficacy of orally administered ENT-01 for the treatment of Parkinson's Disease (PD)(NCT#03047629). ENT-01 is an orally administered, synthetic derivative of squalamine that acts locally on the enteric nerve cells of the gut, stimulating gut motility and altering afferent neural signaling from gut to brain. The compound displaces proteins that are electrostatically bound to intracellular membranes and, through this mechanism, suppresses aggregation of alpha-synuclein monomers into neurotoxic oligomers.
The trial enrolled 50 patients with Parkinson's disease and constipation over a nine-month period. There were no safety issues and adverse events were largely confined to the GI tract. Systemic absorption was minimal, suggesting that the effect of the drug was local. The primary efficacy endpoint was the reversal of constipation. This was achieved in over 80% of patients, and the dose correlated positively with constipation severity at baseline, consistent with the hypothesis that constipation in PD results from the progressive accumulation of alpha-synuclein in the enteric nervous system (ENS) and that the dose of ENT-01 required to restore neuronal activity is proportional to the load of alpha-synuclein in the enteric nerve cell.
The senior author of the study and Enterin Co-founder, President and CMO, Dr. Denise Barbut, said, "We demonstrate in this study that ENT-01 can restore gastrointestinal motility in patients with PD, suggesting that a major division of the nervous system and the largest sensory organ in the body (the GI tract) is not irreversibly damaged in patients with PD, despite the long-standing constipation that might suggest otherwise. We believe that this is the first demonstration of the reversal of a neurodegenerative process in humans."
The study also found potential signals of clinical benefit for parkinsonism, cognition, hallucinations, sleep, REM-behavior disorder and circadian rhythm. According to the lead author, Dr. Robert Hauser, Professor of Neurology and Director of the Parkinson's Disease and Movement Disorders Center at the University of South Florida, "While these results are intriguing, this was an open label trial and placebo effects cannot be excluded. These findings must undergo rigorous evaluation in future place-controlled trials."
The company is currently conducting a larger, randomized, double-blind, placebo-controlled trial (KARMET) to further explore the effect of ENT-01 on constipation and neurologic symptoms in patients with Parkinson's disease. The details of the study can be found on Clinicaltrials.gov (NCT#03781791).
About Enterin Inc.
Enterin Inc. is the first company to develop a novel drug that repairs the dysfunctional gut-brain axis in patients with neurodegenerative disease. Enterin Inc. is pioneering the medical community's understanding of the link between infections, dysfunction of the enteric nervous system (ENS) of the gut and the early onset and chronic progression of neurodegenerative disease. The lead compound, ENT-01, displaces membrane-bound alpha-synuclein (αS) aggregates from nerve cells in the ENS and improves neural signaling between the gut and the brain in preclinical models of Parkinson's disease. Enterin Inc. is now progressing ENT-01 through clinical trials in an attempt to reverse the constipation and neurologic symptoms of Parkinson's disease.
For more information, please visit www.enterininc.com.
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