Extracellular RNA Biomarkers of Myotonic Dystrophy
Abstract
Topic Area: Myotonic dystrophy Area of Encouragement: The identification of biomarkers that can be detected through minimally invasive means to signal early changes in the progression of myotonic dystrophy. Scientific Objective: Our goal is to use urine samples from myotonic dystrophy patients to identify markers of disease activity that can be used to detect early changes in the progression of myotonic dystrophy and determine whether new treatments are working. Rationale: Small particles called extracellular vesicles (EVs) are released from many different cell types into the urine and blood. EVs contain molecules called extracellular RNAs (exRNAs) that can serve as biomarkers of cancers and other disease states. Recently, our group was the first to demonstrate that EVs in urine also contain a certain type of exRNA that can serve as specific biomarkers of myotonic and other muscular dystrophies. However, to date relatively little is known about the extent of the changes in exRNA that occur in myotonic dystrophy patients as compared to healthy individuals, including the relationship of exRNA markers to the underlying disease state or rate of progression. Clinical Applicability: Current approaches to detect disease activity or early changes in progression of myotonic dystrophy involve molecular analysis of muscle tissue biopsies, a procedure that is invasive, painful, and requires general anesthesia in pediatric patients, which increases risk. Non-invasive measurements of muscle function and structure, such as strength tests, walking tests, or MRI (magnetic resonance imaging) detect cumulative effects of chronic disease over several years, which limits the ability to detect early changes of disease progression or response to therapy. Urine exRNAs are a rich and renewable biomarker source that has the potential to enable convenient non-invasive monitoring of disease progression and determine at an early stage or whether a new drug is having its intended effect during the course of treatment. Projected time for a patient-related outcome: We believe our exRNA biomarkers will be ready to be tested in clinical trials of new candidate drugs by the end of this 3-year project, perhaps even earlier. We envision that they could be incorporated into upcoming clinical trials so that their usability could be compared directly with muscle biopsies in the same patients. Likely contributions of this study to advancing the field of DM research or patient care: If successful, our exRNA biomarkers will alert investigators at an early stage and throughout the study whether the drugs are having the intended effect so that the dose may be adjusted upward or downward as needed. This would speed the evaluation of drug efficacy and decrease the time it takes to have a new drug available for patient use. exRNA biomarkers also could reduce or eliminate the need for patients to have muscle biopsies to evaluate treatment response, which would lessen pain and improve patient quality of life.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010293
Entities
People
- Thurman Wheeler
Organizations
- Massachusetts General Hospital
- United States Army