Identification of New Biomarkers Monitoring DMD Pathology and Response to Treatment

Duchenne muscular dystrophy (DMD) is caused by the absence of the protein dystrophin, mainly expressed in skeletal muscles. Unfortunately, despite more than 30 years of research, DMD remains an uncurable disease. One of the obstacles in the development of new therapeutic approaches is the lack of sensitive endpoints, i.e. it is difficult to establish the efficacy of a treatment.

Here we propose a project in which we will determine the changes in muscle protein content in a murine model of DMD. We will label only muscle proteins for specific time periods and determine the amount and presence of labelled proteins in both the muscle and the serum of mice. To understand the significance of the identified proteins for muscle pathology, we will use two different pharmacological treatments to improve muscle state. Furthermore, we will use a genetic approach to restore dystrophin expression. In both cases we will examine the changes in biomarkers in muscle and serum, allowing us to understand which biomarkers are closely linked to muscle pathology.

Lastly, we will examine how the biomarkers we identified in dystrophic mice are changed in DMD patients. We have access to a biobank with both serum and muscle from DMD patients.

Taken together, the proposed project will identify new biomarkers which will help evaluation of clinical trials, offering new evaluation criteria. Furthermore, the presence of sensitive biomarkers will also allow to better identify patients to be recruited for clinical trials.