Evaluation and discovery of blood-based biomarkers for ataxia

Summary Genetic ataxias are slowly progressing neurodegenerative diseases causing severe disability for which no disease-modifying therapy exists. Though individually they are rare diseases, together they affect nearly 15,000 people worldwide. Current clinical scales for assessment of ataxia severity and progression are ineffective for evaluation of treatment effects during the timeframe of typical clinical trials, necessitating inclusion of high numbers of patients, which often is not feasible, to achieve statistically meaningful outcomes. These challenges could be addressed if reliable, sensitive, and preferably minimally invasive biomarkers for ataxia severity and progression were available for use in clinical trials. Unfortunately, such biomarkers do not presently exist. Therefore, we propose an initial study combining both biomarker discovery using proteomic and transcriptomic approaches, and testing of several promising candidate biomarkers in blood samples from patients with the most common dominant and recessive types of genetically inherited ataxia. We will utilize state-of-the-art techniques including Olink®’s proximity extension proteomics, NextGen RNA sequencing, and electrochemiluminescence immunoassays. The analyses will be done in patient plasma and neuronal extracellular vesicles isolated from the plasma, increasing the likelihood of discovering biomarkers reporting on specific biochemical changes in the central nervous system. The study will generate an initial set of potential biomarkers, providing the basis for subsequent, larger testing and validation in the context of R01 or U01 applications, addressing a current urgent gap in developing effective therapies for patients with genetic ataxias. Additionally, the proteomic and transcriptomic data will allow pathway analysis that may shed new light on the mechanisms underlying the pathogenesis of specific types of genetic ataxia, including both common and distinct features among them. Project Number: 1R21NS144989-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: GAL BITAN (+1 co-PI) | Institution: UNIVERSITY OF CALIFORNIA LOS ANGELES, LOS ANGELES, CA | Award Amount: $196,875 | Activity Code: R21 | Study Section: Clinical Neurodegeneration Translational Neuroscience Study Section[CNTN] View on NIH RePORTER: https://reporter.nih.gov/project-details/11371286