Exploring the Role of Immune Response in Parkinson Disease

Research consortium launches multisite investigations of the impact of aberrant immunity

The association between Parkinson disease and immunity is the focus of a multicenter research project supported by a new consortium grant from the Aligning Science Across Parkinson’s (ASAP) initiative. With this award, the researchers will study how mutations in the LRKK2 and Parkin genes may cause immune dysfunction that leads to Parkinson disease.

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“These investigations will provide important molecular insights into possible new targets for treating Parkinson disease, says co-investigator Timothy Chan, MD, PhD, who leads the Center for Immunotherapy and Precision Immuno-Oncology in Cleveland Clinic Lerner Research Institute. “Additionally, they will help inform whether immunotherapies originally developed for treating cancer may also have application in patients with Parkinson disease.”

Dr. Chang is the research consortium’s core investigator at Cleveland Clinic. The consortium is led by researchers at Massachusetts General Hospital and Harvard Medical School and also includes investigators from the University of Houston and MD Anderson Cancer Center at the University of Texas.

In search of early predictive biomarkers and treatment targets

Parkinson disease is characterized by uncontrollable neuron damage or death, primarily related to neurons that produce dopamine (i.e., dopaminergic neurons). Aberrant immunity plays a major role in the disease’s pathogenesis. Loss of nerve cells and neuronal connectivity in the area of the brain that controls movement ultimately results in the symptoms commonly observed with the disease.

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The researchers will use various preclinical models to study how dopaminergic neuron behavior and immune responses are modulated by mutations in the LRRK2 and Parkin genes, both of which are linked to Parkinson disease as well as certain cancers. The investigators will also collect samples, including serum and cerebrospinal fluid, from Parkinson disease patients with and without LRKK2 mutations. By comparing these together, they aim to identify immune and dopaminergic neuron traits that may be linked to the Parkinson- and cancer-associated genes, with the hope that these traits could serve as early predictive biomarkers and targets for immunotherapy and other treatments.

Investigational strength in numbers

“We are excited to be joining the other institutions as partners in this important research,” says Dr. Chan, who is also staff in Cleveland Clinic’s Genomic Medicine Institute. “Considering that immunotherapies are emerging for many disease types, we believe this project is quite timely, given its objective of defining the role of the immune response in Parkinson disease.”

While all consortium members will collaborate closely, core investigators from each institution will lead various subprojects. Dr. Chan will oversee the Parkin-focused research.

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The new award is one of the first large consortium grants to go to researchers from the Center for Immunotherapy and Precision Immuno-Oncology, which launched at Cleveland Clinic earlier this year. The grant was issued by ASAP’s implementation partner, The Michael J. Fox Foundation for Parkinson’s Research.