TGen leads international team to characterize blood-based clues of Parkinson’s Disease

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Immune system alterations could provide a path for future diagnostics and studies of this progressively debilitating neurological disease

PHOENIX, Ariz. — Aug. 5, 2021 — The results of a Parkinson’s Disease study led by the Translational Genomics Research Institute (TGen), an affiliate of City of Hope, suggest that the immune system may play a key role in the early stages of disease and progression of this neurologic disorder.

This study, which appears today in Nature Aging, was conducted in collaboration with the University of Southern California and the National Institute on Aging, and funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF).

Parkinson’s, a progressive neurological disease that can severely affect movement, is expected to impact nearly 12 million people worldwide over the next two decades, including more than 1 million in the U.S.  

Parkinson’s symptoms usually worsen over time, culminating with many patients having difficulty with movement, balance and speech. An incomplete understanding of the molecular mechanisms that govern how Parkinson’s begins and progresses has hampered development of diagnostics and therapeutics.

This study involved blood-based RNA sequencing analysis — spelling out the genetic code — of 4,871 samples from more than 1,500 patients from the Parkinson’s Progression Markers Initiative (PPMI), one of the world’s largest and best characterized Parkinson’s studies.

“There is so much data for the research community to mine in this resource, especially when combined with the corresponding small RNA sequencing, genomic, and imaging data,” said the study’s senior author Kendall Van Keuren-Jensen, Ph.D., TGen Professor of Neurogenomics, and Director of TGen’s Center for Noninvasive Diagnostics.

A second study of nearly 1,600 Parkinson’s patients was employed for validation of the findings.

The robust clinical data associated with the PPMI participants and longitudinal sample collection offers unparalleled opportunities for the field to employ this dataset in biomarker studies.

“Our goal was to create and highlight a comprehensive RNA transcriptomic resource from whole blood samples that the Parkinson’s Disease research community can easily access and utilize, towards improved biomarkers of the disease,” said Elizabeth Hutchins, Ph.D., a TGen Computational Scientist, and one of the study’s lead authors. “This study was designed for researchers to interrogate genes, pathways and mechanisms that play a role in the genesis and progression of disease.”

David Wesley Craig, Ph.D., Professor of Translational Genomics at the Keck School of Medicine at the University of Southern California, said the study already is proving valuable.

“Validated biomarkers of Parkinson’s Disease progression are critical for finding better therapies and diagnosis in PD. This study provides one of the largest and most comprehensive resources empowering this effort from whole-blood,” said Dr. Craig, one of the study’s lead authors. “Already, it has provided us with new insights into disease pathology, and partnering with other researchers, will lead to new tools for improving outcomes and treatments in PD.”

Parkinson’s patient’s immune system altered

Parkinson’s participants showed significant transcriptomic changes associated with circulating immune cells in their blood, compared to individuals without the disease. One key finding demonstrated a subtle but significant alteration in the immune cell composition in Parkinson’s participants, with an elevated ratio of neutrophils to lymphocytes. The shift in immune cells was evident at the RNA level in the blood. Alterations in the levels of these white blood cells may provide clues as to the progression of the disease, and provide a potential biomarker of the disease.

“Our analysis revealed early and persistent immune cell changes associated with disease,” explained Dr. Van Keuren-Jensen. She suggested that more study is needed of how the immune system plays a role in Parkinson’s Disease: “From our data, we do not know detailed cell population changes or how individual cell changes are transcriptionally altered. Further, targeted analysis of immune cell populations, and single-cell transcriptional changes, should be evaluated.”

Data from this study is housed at the Mark and Mary Stevens Neuroimaging and Informatics Institute at USC.

Also contributing to this study were: the National Institute on Aging, Indiana University, Prairie View A&M University, Saarland University (Germany), and the HudsonAlpha Institute for Biotechnology.

This study — RNA sequencing of whole blood reveals early alterations in immune cells and gene expression in Parkinson’s disease — was supported by the MJFF, the National Institute on Aging, and the National Institutes of Health. Additional support was provided by more than 30 industry partners, the Accelerating Medicines Partnership for Parkinson’s, and by the Parkinson’s Disease Biomarker Program, which itself was supported by the National Institute of Neurological Disorders and Stroke.

 

Posted in AZBio News.