A randomized controlled trial of 150 persons with Parkinson disease has found that (oral squalamine phosphate) ENT-01 is safe for up to 25 days of treatment and significantly improves constipation and possibly neurological symptoms. The findings are published in Annals of Internal Medicine.
Parkinson disease is a progressive neurodegenerative disorder caused by accumulation of a-synuclein (aS) in the enteric (ENS) and central nervous system (CNS). In addition to motor symptoms, persons with Parkinson disease may experience constipation, disturbances in sleep architecture, cognitive dysfunction, psychosis, and depression, all of which result from impaired function of neural pathways not restored by replacement of dopamine. Previous research has demonstrated that ENT-01 rapidly and safely improves bowel function, and also improves neuropsychiatric symptoms such as dementia and psychosis.
Researchers from the Mayo Clinic and other centers conducted a randomized controlled trial of 150 persons with Parkinson disease and constipation who were given either ENT-01 or a placebo daily for up to 25 days. The authors found that orally administered ENT-01 is safe and that it rapidly normalizes bowel function in a dose-dependent fashion with an effect that seems to persist for several weeks beyond the treatment period.
They note that this suggests that the ENS is not irreversibly damaged in PD, even though the long-term constipation might suggest otherwise. They also report that adverse events, including nausea and diarrhea, were largely confined to the gastrointestinal tract, supporting the local action of ENT-01.
The authors advise that in future studies, starting at lower doses and escalating more slowly may reduce the frequency of both symptoms. They also advise that, given the brief treatment period, the safety of ENT-01 will need to be evaluated for longer exposures in future studies.