FDA Accepts Investigator Sponsored IND of ENT-01 to Treat a Patient with Prodromal Multisystem Atrophy
The Food and Drug Administration (FDA) has accepted an investigator sponsored Investigational New Drug (IND) application (166532) for the use of ENT-01 (squalamine phosphate, Enterin Inc, Philadelphia, PA) to treat a patient with prodromal multisystem atrophy (MSA). Previous phase 2a and 2b studies demonstrated that ENT-01 was effective in treating constipation associated with Parkinson disease (PD) in approximately 200 participants. Prodromal MSA and PD are both alpha-synucleinopathies.
The application’s acceptance permits the use of ENT-01 to treat a 42-year-old male patient who was diagnosed with prodromal MSA due to his 2-year history of disease-related symptoms including genitourinary dysfunction, constipation, dysfunctional circadian rhythm, and sleep disturbances indicative of a rapid eye movement (REM)-behavior disorder. The diagnosis also was based on positive alpha-synuclein staining in duodenal enteric neurons and the patient’s predisposition to PD and prodromal MSA caused by a mutation of the ATP13A2 gene. ENT-01 prevents alpha-synuclein aggregates from forming and depositing on the enteric neurons, and it also electrostatically displaces misfolded, positively charged proteins. Preliminary experiments have examined the effect of ENT-01 on the patient’s cells, and the results suggest that the drug is effective in preventing the oxidative stress response caused by rotenone. Exposure to rotenone, which is a common component in pesticides and insecticides, causes parkinsonian symptoms in rats, and it is used in animal models of PD.
“This is the first time that any compound is being used to prevent the progression of MSA,” said Dr. Denise Barbut, Co-Founder, President, and CMO of Enterin Inc. “A milestone in the development of ENT-01 for both treatment and prevention of other neurodegenerative disorders.”
Prodromal MSA causes progressive autonomic failure, and individuals diagnosed with this condition have an average life expectancy of 6-8 years. There is currently no existing treatment to prevent MSA disease progression.