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Stool Transplant Improves Motor Function in Parkinson's Disease Patients

A stool sample.
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A Phase 2 clinical study named GUT-PARFECT found that fecal microbiota transplantation (FMT) improved motor symptoms in Parkinson’s disease patients.

“Our results are really encouraging!” Dr. Arnout Bruggeman, a researcher at the VIB-UGENT Center for Medical Biotechnology at the University of Ghent, and first author of the study, said. “After 12 months, participants who received the healthy donor stool transplant showed a significant improvement in their motor score, the most important measure for Parkinson's symptoms.”

The research, published in eClinical Medicine, was led by neurologist Professor Patrick Santens from the University Hospital Ghent and Professor Roosmarijn Vandenbroucke, group leader at VIB.

A new approach to treating neurodegeneration

FMT – also known as a stool transplant – involves collecting feces from a healthy donor and inserting it into a patient’s gastrointestinal tract (GI).

The logic behind the clinical use of FMT is that a disease underpinned by microbial dysbiosis in the gut could be improved or treated by introducing healthy bacteria and restoring the gut microbiome. While the procedure might sound grim, it has demonstrated effectiveness for a range of conditions. In clinical practice, it is mainly adopted for the treatment of persistent infections with Clostridium difficile.

Despite decades of research and countless clinical trials, neurodegenerative diseases such as Alzheimer’s and Parkinson’s lack efficacious treatments. Recently, the research community’s attention has turned towards novel or alternative factors, which may affect the onset or management of these conditions, such as the gut–brain axis.

Parkinson’s disease is characterized by the formation of alpha-synuclein protein clumps, which damage nerve cells producing the neurotransmitter dopamine in the central nervous system. A lack of dopamine causes the hallmark symptoms of Parkinson’s, such as loss of muscle control, tremors and stiffness.

A growing body of research demonstrates GI dysfunction is prevalent in Parkinson’s patients prior to symptom development. Alpha-synuclein protein clumps have also been observed in the GI system during the early stages of Parkinson’s, which, in animal models, appear to reach the brain via the vagus nerve.

These emerging links between Parkinson’s and the gut microbiome inspired the neurology department at UZ Gent; they wanted to explore whether FMT could significantly impact the evolution of Parkinson’s disease over the course of one year.

Parkinson’s disease patients’ motor scores improved 12 months after FMT

The GUT-PARFECT trial was a double-blind, placebo-controlled and randomized Phase 2 clinical study. A total of 46 Parkinson’s disease patients, aged 50–65 years, were recruited and randomly assigned to receive nasojejunal FMT from a healthy donor (22 participants) or their own stool (24) as a placebo. Santens and colleagues analyzed changes in the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score as the primary outcome. Scores were collected at baseline, and at 3-, 6- and 12-months post-FMT.

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“The change in MDS-UPDRS motor score from baseline to 12 months post-FMT was significantly different between treatment groups,” the authors described. The improvement was most pronounced between the 6-to-12 months interval, which suggests that FMT could have long-lasting effects in Parkinson’s disease patients. FMT from healthy donors also reported a reduction in constipation, an inconvenient symptom for many Parkinson’s patients.

An important and unresolved issue in this study, as professed by the research team, is that the placebo group also demonstrated a large and relatively long-lasting response to autologous FMT.  The MDS-UPRDS motor scores were significantly different between the treatment and placebo groups only at the 12-month follow-up mark, and not before.

“While we can only speculate, it's plausible to hypothesize that the clinical differences observed might be aligned with the effects on gut motility, as evidenced by the radiopaque pellet test results at the six-month evaluation. Another critical aspect to consider is the recent findings indicating significant alterations in the gut microbiome following autologous FMT,” the authors said.

"Our study provides promising hints that FMT can be a valuable new treatment for Parkinson's disease,” Vandenbroucke said. "More research is needed, but it offers a potentially safe, effective and cost-effective way to improve symptoms and quality of life for millions of people with Parkinson's disease worldwide."

Reference: Bruggeman A, Vandendriessche C, Hamerlinck H, et al. Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson’s disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial. eClinicalMedicine. 2024;71. doi: 10.1016/j.eclinm.2024.102563

This article is a rework of a press release issued by the VIB-UGENT Center for Medical Biotechnology at the University of Ghent. Material has been edited for length and content.