Gastrointestinal Dysfunction in Parkinson’s Disease: Current and Potential Therapeutics

Abstract

Abnormalities in the gastrointestinal (GI) tract of Parkinson’s disease (PD) sufferers were first reported over 200 years ago; however, the extent and role of GI dysfunction in PD disease progression is still unknown. GI dysfunctions, including dysphagia, gastroparesis, and constipation, are amongst the most prevalent non-motor symptoms in PD. These symptoms not only impact patient quality of life, but also complicate disease management. Conventional treatment pathways for GI dysfunctions (i.e., constipation), such as increasing fibre and fluid intake, and the use of over-the-counter laxatives, are generally ineffective in PD patients, and approved compounds such as guanylate cyclase C agonists and selective 5-hyroxytryptamine 4 receptor agonists have demonstrated limited efficacy. Thus, identification of potential targets for novel therapies to alleviate PD-induced GI dysfunctions are essential to improve clinical outcomes and quality of life in people with PD. Unlike the central nervous system (CNS), where PD pathology and the mechanisms involved in CNS damage are relatively well characterised, the effect of PD at the cellular and tissue level in the enteric nervous system (ENS) remains unclear, making it difficult to alleviate or reverse GI symptoms. However, the resurgence of interest in understanding how the GI tract is involved in various disease states, such as PD, has resulted in the identification of novel therapeutic avenues. This review focuses on common PD-related GI symptoms, and summarizes the current treatments available and their limitations. We propose that by targeting the intestinal barrier, ENS, and/or the gut microbiome, may prove successful in alleviating PD-related GI symptoms, and discuss emerging therapies and potential drugs that could be repurposed to target these areas.

Efficacy and safety of probiotics in Parkinson’s constipation: A systematic review and meta-analysis

“…Unfortunately, there is no effective neuroprotective or disease treatment to stop the progression of PD ( Han et al, 2022 ). Conventional treatments for constipation are also often ineffective for Parkinsonian patients.…”

Antibodies against HSV-1 and Curli Show the Highest Correlation in Parkinson’s Disease Patients in Comparison to Healthy Controls

“…Parkinson’s disease (PD) is the second-most common neurodegenerative disease, with a prevalence of more than 1% in the population above 65 years of age which is projected to double by 2030 [ 1 ]. PD patients frequently suffer from motor dysfunctions, including resting tremors, bradykinesia, rigidity, and gait abnormalities, as well as non-motor symptoms such as hyposmia, sleep disorders, depression, cognitive impairment (CI), and gastrointestinal (GI) symptoms [ 2 , 3 , 4 , 5 ].…”

“…PD is a multifactorial disorder resulting from a combination of genetic and environmental factors [ 5 , 6 ]. Over the past decade, it has become increasingly apparent that the gut microbiota and microbial pathogens may contribute to neurodegenerative diseases, either directly or through immune activation [ 7 ].…”

Optimizing Treatment of Parkinson’s Disease

“…This Special Issue is dedicated to the optimization of PD treatment and contains several examples of the individualization of treatments with standard PD drugs based on novel sensor and information technology [1][2][3], as well as studies of factors important for making individualized decisions for advanced treatment with continuous dopaminergic drug infusion and deep brain stimulation, DBS [1,[4][5][6]. Several symptoms of PD can be difficult to treat and both the review of gastrointestinal dysfunction and the systematic review of the effect of foot orthoses and shoes in PD address some of those areas [7,8].…”

“…One of the major problems with the oral administration of levodopa in PD patients in the fluctuation phase is the erratic gastric emptying, which is why infusion therapies have been developed. In the review by Han et al, it is reported that 70-90% of PD patients have gastroparesis [8]. The current resurgence of the interest in understanding the role of the gastrointestinal tract in PD will likely result in new additional treatments for PD in the near future.…”