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.
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.
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 th enteric
nervous system is not irreversibly damaged in parkinson disease, 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.
In conclusion 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.
Reference:
Oral ENT-01 safe, significantly
improves constipation in persons with Parkinson disease; Annals of Internal
Medicine; DOI: 10.7326/M22-1452