PHILADELPHIA, PA — Enterin Inc., a privately held, Philadelphia-based, clinical-stage biopharmaceutical company, recently announced the acceptance by the U.S. Food and Drug Administration (FDA) of an investigator-sponsored Investigational New Drug (IND) application (166532) to treat a patient with prodromal multisystem atrophy (MSA) with ENT-01. Treatment will continue indefinitely or until significant adverse events occur that warrant discontinuation of the drug.
Individuals diagnosed with MSA have an average life expectancy of 6-8 years and there is no existing treatment that halts the progression of the disease. The condition, an alpha-synucleinopathy similar to Parkinson’s disease, consists of progressive autonomic failure with prominent bowel and bladder symptoms, and central nervous system manifestations include REM-behavior disorder, dysfunctional circadian rhythm, Parkinsonism, and cognitive dysfunction.
ENT-01 has been used to treat close to 200 patients with Parkinson’s disease in Phase 2a and Phase 2b (randomized) studies and dose-dependent improvement noted in the symptoms mentioned above (https://annals.org/aim/article/doi/10.7326/M22-1438). Side effects are largely confined to the GI tract, and consist of nausea, diarrhea, and vomiting. Phase 3 studies in Parkinson’s disease-related constipation and further Phase 2 studies in Parkinson’s disease-related psychosis and dementia are being planned.
The patient is a 42-year-old man with a single gene mutation (ATP13A2) which may impair lysosomal clearance mechanisms, and which predisposes to Parkinsonism and MSA. He has a 2-year history of constipation, urinary symptoms, erectile dysfunction, sleep disturbances suggestive of REM-behavior disorder, dysfunctional circadian rhythm and positive alpha-synuclein staining in duodenal enteric neurons. On the basis of these symptoms, he has been diagnosed as having prodromal MSA.
ENT-01 (squalamine phosphate) acts locally on enteric neurons and electrostatically displaces misfolded, positively charged proteins such as alpha-synuclein from neuronal membranes, as well as preventing the formation and deposition of alpha-synuclein aggregates. Moreover, in preliminary experiments conducted on the patient’s own cells, ENT-01 completely prevented the oxidative stress response caused by rotenone, a highly toxic agent which impairs mitochondrial function, and which is used in animal models of PD.
According to Dr. Denise Barbut, Co-Founder, President and CMO of Enterin, “This is the first time that any compound is being used to prevent the progression of MSA and a milestone in the development of ENT-01 for both treatment and prevention of other neurodegenerative disorders.”
Dr. Robert Hauser, the treating physician and Director of the Parkinson’s Disease and Movement Disorders Center of the University of South Florida added, “We hope that ENT-01 will be helpful in preventing progression of MSA in this individual and that this work will help promote personalized medicine for neurodegenerative diseases.”
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