Extracellular RNA Biomarkers of Duchenne Muscular Dystrophy
Abstract
Scientific objective: Our goal is to use urine and/or blood samples from Duchenne muscular dystrophy (DMD) patients to identify markers of muscle cell dysfunction that can be used to 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). In urine and blood, EVs contain exRNA 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 Duchenne and other muscular dystrophies. Our data suggest that exRNAs are a rich and renewable biomarker source for Duchenne muscular dystrophy that could enable monitoring of the disease state and the molecular response to a new treatment. Focus Area: Assessment of clinical trial tools and outcome measures, specifically the discovery and qualification of pharmacodynamic and predictive biomarkers. Clinical applicability: The research described here has the potential to help every DMD patient who is being treated with newly developed therapies. The potential clinical application includes collecting urine and/or blood samples to monitor whether a new drug is having its intended effect during the course of treatment. For boys being treated with exon skipping antisense oligonucleotides, the markers being developed can be “personalized” to identify the specific mutation that being targeted for skipping. Our approach would provide a minimally invasive measurement of response to treatment that could be determined in a matter of days. This could reduce or eliminate the need for patients to have muscle biopsies to evaluate treatment response, which would reduce pain and improve the quality of life. Projected time for a patient-related outcome: We believe our exRNA markers will be ready to be tested in clinical trials of antisense oligonucleotides by the end his 3-year project, perhaps even earlier. We envision that they could be incorporated into existing or 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 DMD 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 drug available for clinical use.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 16, 2019
- Source ID
- W81XWH1910392
Entities
People
- Thurman Wheeler
Organizations
- Massachusetts General Hospital
- United States Army