Posted July 7, 2023

Anumantha Kanthasamy, Ph.D., University of Georgia
Richard Gordon, Ph.D., Queensland University of Technology, Australia

Research has demonstrated a link between functional impairments and imbalances in the gut microbiome and the onset and progression of Parkinson’s disease (PD), though the causal mechanism remains unclear. Recently, a team of researchers led by Dr. Anumantha Kanthasamy at the University of Georgia and Dr. Richard Gordon at Queensland University of Technology found more abundant levels of bacterial strains that synthesize certain neurotoxic chemicals such as trimethylamine (TMA) in PD patients. Gut TMA can be metabolized into formaldehyde and trimethylamine-N-oxide, which they found to be elevated in people with PD. These chemicals could also accelerate the aggregation of the protein a-synuclein, activate the inflammation-triggering NLRP3 pathway, and disrupt the regulation of the lysosomal enzyme GBA1 – all of which are hallmarks of PD pathology. With funding from this Synergistic Idea Award, Drs. Kanthasamy and Gordon’s research teams in the U.S. and Australia will establish the causal link between these various processes and use mouse models as well as PD patient samples to evaluate therapeutic applications of various TMA inhibitors, including a safe probiotic strain of the bacteria E. coli (E. coli Nissle 1917, or EcN). A successful outcome will provide a better understanding of the role of the gut microbiota and PD progression and enable the development of new treatment strategies with potential for rapid translation towards human use.

https://research.qut.edu.au/cmr/
twitter.com/Gordon_NeuroLab

Links:
Public and Technical Abstracts: Novel Therapeutic Targeting of Neurotoxic Gut Microbiota-Derived Metabolites in Parkinson’s Disease (PD210010)
Public and Technical Abstracts: Novel Therapeutic Targeting of Neurotoxic Gut Microbiota-Derived Metabolites in Parkinson’s Disease (PD210010P1)

Diane B. Re, Ph.D., Columbia University Medical Center
Gary W. Miller, Ph.D., Columbia University Medical Center

Researchers believe that certain genetic mutations predispose individuals to develop Parkinson’s disease (PD). However, not all people with these mutations will necessarily develop PD. This suggests that other factors are responsible for interacting with the genetic mutation to trigger PD and determine its severity. With support from a Synergistic Idea Award, Dr. Diane Re has partnered with Dr. Gary Miller of Columbia University Medical Center and Dr. Hardy Rideout of the Biomedical Research Foundation, Academy of Athens, to test whether toxic metal and chemical exposure and accumulation interact with genetic mutations to the protein leucine-rich repeat kinase 2 (LRRK2), which has been linked to PD. Their multi-pronged study will attempt to correlate LRRK2 dysfunction and associated PD with the elimination of toxicants from neurons through the use of lipid bilayer-delimited particles called extracellular vesicles (EV). These EVs have been referred to as liquid biopsies since they contain brain-derived material that is accessible in the blood. They will then determine whether mutated LRRK2 is uniquely vulnerable to toxic mixtures of metals and organic chemicals, and finally to test the effects of chronic toxicant mixture exposure in mouse models carrying the LRRK2 mutation. Validated EV biomarkers could be valuable for diagnosing PD and use in clinical trials of new drugs.

Links:
Public and Technical Abstracts: Novel Exposomics and Extracellular Vesicle Biomarkers to Unravel Gene-Environment Interactions and Mechanisms of Neurodegeneration in Parkinson’s Disease (PD210047)
Public and Technical Abstracts: Novel Exposomics and Extracellular Vesicle Biomarkers to Unravel Gene-Environment Interactions and Mechanisms of Neurodegeneration in Parkinson’s Disease (PD210047P1)

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