Huntington's disease (HD) is a fatal neurodegenerative disease for which no therapy has been proven to delay onset or to slow progression of the disease. The development of therapies is challenged by lack of clear understanding of disease mechanisms and limited availability of biomarkers which could be used to monitor the effectiveness of therapies. MicroRNAs (miRNAs) are short non-coding RNA molecules which are appealing for biomarker discovery and development because of their relative abundance and remarkable stability in biofluids. We hypothesize that, miRNA markers associated with neurodegeneration in HD brain can be detected in the CSF and plasma of HD patients and have preliminary data demonstrating disease-related miRNA signatures in both biofluids. Here we propose examining the miRNA signatures present in concurrent CSF and plasma samples from HD patients and comparing them with each other and with miRNA changes in postmortem HD brain. Our goal is to understand the inter-relationships of the plasma and CSF miRNome in HD patients and the overlap of these with brain miRNA. We hope to identify candidate plasma and CSF markers that could correlate with neurodegeneration in brain.

Public Health Relevance

MicroRNAs (miRNAs) are short non-coding RNA molecules which are appealing for biomarker discovery and development because of their relative abundance and remarkable stability in biofluids. In this study, we propose examining the miRNA signatures present in concurrent CSF and plasma samples from HD patients and comparing them with each other and with miRNA changes in postmortem HD brain. Our goal is to understand the inter-relationships of the plasma and CSF miRNome in HD patients and the overlap of these with brain miRNA. We hope to identify candidate plasma and CSF markers that could correlate with neurodegeneration in brain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS103056-01
Application #
9374780
Study Section
Clinical Neuroscience and Neurodegeneration Study Section (CNN)
Program Officer
Miller, Daniel L
Project Start
2017-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02114
Weiss, Andreas; Abramowski, Dorothée; Bibel, Miriam et al. (2009) Single-step detection of mutant huntingtin in animal and human tissues: a bioassay for Huntington's disease. Anal Biochem 395:8-15