NIH grant: Red Blood Cell Lipid Signatures: A New Approach to Parkinson's Disease Diagnosis (1R61NS142626-01A1)

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NIH grant 1R61NS142626-01A1: Red Blood Cell Lipid Signatures: A New Approach to Parkinson's Disease Diagnosis
Institute: {'code': 'NS', 'abbreviation': 'NINDS', 'name': 'National Institute of Neurological Disorders and Stroke', 'admin_org_id': '12500053', 'admin_funding_url': ''}. PI: Lenora  Higginbotham. Award: $927014.
Start: 2026-08-15T00:00:00.
Idiopathic Parkinson’s Disease (iPD) affects approximately 900,000 Americans, making it the second most common
neurodegenerative disease. Efforts toward detection and therapeutic development for iPD are hampered by the current lack
of effective molecular diagnostic tools. We propose to validate a diagnostic lipid biomarker panel that we discovered in red
blood cells (RBCs) from the Australian Victorian Parkinson’s Disease Registry (n=280). We initially investigated RBCs
because they have high abundance of alpha-synuclein (α-syn) protein, which is a major component of Lewy bodies and a
pathological hallmark in iPD brain. With Micheal J. Fox research support, we discovered RBC lipids were altered in iPD
patients. Using high-resolution LC-MS discovery lipidomics with AI-based marker selection, we identified eight lipids in
RBCs that distinguished iPD from controls with 89% accuracy. To build on this discovery, we propose a structured approach
to validate and translate this biomarker panel for clinical use. In the R61 phase, we will: 1) develop a quantitative LC-MS
assay for these 8 lipid biomarkers in blood, ensuring analytical performance and consistency between research and clinical
labs. 2) establish normal reference ranges for each of these biomarkers using a representative patient population, leveraging
samples from the Emory Goizueta Alzheimer’s Disease Research Center. 3) refine the current lipid panel to identify the
optimal set of these biomarkers required for accurate discrimination between iPD and controls. 4) we will validate the
diagnostic accuracy and disease specificity against Alzheimer’s disease and dementia with Lewy body disease. If we reach
the milestone of greater than 90% sensitivity and 80% specificity, we will progress to the R33 phase to evaluate the clinical
sensitivity and specificity of the lipid biomarker panel in a third cohort using samples from the BIOSEND Parkinson’s
Disease Biomarkers Program. Our team, which includes Drs. Roberts, Higginbotham, Roback, and Easley, combines
expertise in bioanalytical methods, clinical iPD research, neurodegeneration, clinical pathology, and biostatistics. As a team
we are well positioned to successfully complete the proposed research and translate to a laboratory developed test. The
blood-based lipid biomarker assay will offer a reliable, and quantitative diagnostic tool, potentially revolutionizing iPD
diagnosis and management. By achieving ≥90% sensitivity and 80% specificity in the detection of iPD, we aim to advance
this blood-based assay to detect iPD towards in vitro diagnostic FDA certification.

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