Clinical Utility of Serum Protein Biomarkers in Very Young Duchenne Muscular Dystrophy Boys
Abstract
Very young Duchenne muscular dystrophy (DMD) patients, from birth to 4 years old, are often excluded from potential treatment and clinical trials despite the fact that early intervention might actually prove beneficial. The main reasons for this exclusion include (1) late diagnosis (often patients are not diagnosed until their second or third birthday); (2) little information about the muscle health in very young infants; and (3) lack of meaningful and standardized tools to assess disease severity and progression in this very young DMD population. Very often assessments of disease progression in DMD infants and toddlers are of observational nature communicated by parents to doctors. Current clinical tests to assess disease progression and response to therapies in DMD require complex physical tests and sometimes invasive procedures such as muscle biopsies that are not suitable for infants and toddlers. Defining alternative methods to assess disease severity and progression in DMD boys under 4 years of age will facilitate their enrollment in clinical trials and might inform us about new ways to treat DMD. In this study, we propose to measure blood circulating biomarkers as a means to assess disease severity and progression in very young patients. Indeed, in our ongoing biomarker studies, we identified about 67 biomarkers in blood that can inform us about muscle degeneration, muscle inflammation, and fibrosis. These biomarkers changed in their levels with disease progression and age. Interestingly, these biomarkers were found to be at their highest levels in 4-year-old DMD boys compared to age-matched healthy controls, suggesting that even though DMD patients are walking at this young age, their muscle is quite damaged and leaking. We hypothesize that these DMD biomarkers can be detected in even younger patients, from birth to 4 years of age, and can be used to monitor disease progression and response to therapies in this age range. Blood circulating biomarkers are more objective and unbiased compared to questionnaires and other physical tests. They can inform us about muscle health and if a treatment is working. They might also inform us about early mechanism of muscle degeneration and thus provide us with an opportunity to develop novel therapeutic strategies for DMD. To achieve this proposal, we are extending our study protocol currently supported by the Cooperative International Neuromuscular Research Group (CINRG) and the Parent Project Muscular Dystrophy (PPMD) program to enroll very young DMD boys (0-4 years of age) and age-matched controls to collect whole blood at entry and then at follow-up visits. Some basic physical tests suitable for infants and toddlers will also be collected during the visits for later comparison with our biomarkers. Serum will be prepared from collected blood samples and analyzed for biomarker discovery and quantification using or established methods. Biomarkers will be assessed at different ages between 0 and 4 years old and assigned to specific categories including muscle leakage, inflammation, and fibrosis. The level of biomarkers will be compared to the collected physical test to validate their use as outcome measures in this very young DMD population. If successful, our study will identify a set of blood circulating biomarkers that can be used by clinicians and doctors to monitor DMD patients at very young ages and perhaps enroll them in clinical trials before advanced muscle damage occurs. This might lead to better outcome for the patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610557
Entities
People
- Yetrib Hathout
Organizations
- United States Army