Maintenance laxatives can relieve patients with Parkinson’s disease from a progression of rigidity, according to a newly released study audit. The results further point strongly to a contribution of gut factors to the disease mechanisms.
In the recently published retrospective study, researchers from King’s College London, United Kingdom, reviewed laxative use among 79 Parkinson’s disease patients who participated in a gut-brain clinic between August 2002 and July 2014. To allow detection of robust changes, only patients without levodopa-triggered motor symptom fluctuations were included in the study audit.
The study, “Quantifying rigidity of Parkinson’s disease in relation to laxative treatment: a service evaluation,” published May 21 online in the British Journal of Clinical Pharmacology, used a strict scheme of laxative types, starting with bulk or osmotic laxatives and finally prucalopride (Resolor) — a serotonin stimulator improving gut movements approved in Europe. Researchers noted the presence of other medications, including antibiotics or antimicrobial medications.
The patients contributed to 1,493 measurements of rigidity. Arm rigidity increased on average 5.5% per year before patients started using laxatives. Once laxatives were introduces, the development that plateaued. The effect remained through the entire study period.
Adjusting the analysis for the use of other drugs and factors that might have affected the result, did not change the outcomes. The slowing of rigidity progression could be observed also in patients who had never used antiparkinsonian drugs, suggesting that the effect is not changed by medication.
“That the apparent effect of regular laxatives appeared in those who had never received drugs for Parkinson’s disease points to modification of an underlying disease process,” said Dr. John Dobbs, senior author of the study, in a news release.
Different classes of laxatives gave similar results, indicating that relieving constipation affects a common factor linked to rigidity. Such a factor might be gut dysbiosis — an imbalance in the bacterial species inhabiting the gut — linked to inflammatory processes.
“Different aspects of Parkinson’s disease may, of course, have different drivers,” said Dr. Sylvia Dobbs, who also authored the study. “For example, our controlled trial of eradicating Helicobacter from the stomach showed a beneficial effect on the diminished movement characteristic of Parkinson’s disease.”
Actively managed laxative regimens might keep imbalanced gut bacteria in check, offering a cost-effective way to harness disease progression, also opening up new avenues of research.
Constipation in individuals who later develop Parkinson’s might be present for decades before any diagnosis is set, and misfolded α-synuclein – a hallmark of the disease – can be found in the gut nervous system at early stages and predate a diagnosis. Scientists have proposed that the aggregates spread from the gut to the brain through neural connections and continue propagating within the brain.
Signs of inflammation both in and outside the brain can be detected early in Parkinson’s disease. The study suggests that limiting peripheral inflammation in the gut might affect brain inflammation and the spreading of α-synuclein fibrils which contribute to the disease progression.
The study concluded that maintenance laxatives might be employed as an initial treatment targeting rigidity and as an add-on to other Parkinson’s drugs.