Validation of extracellular vesicle-associated circulating biomarkers for FSHD in cross-sectional and longitudinal clinical studies

Investigators: Bilal Bayazit PhD, Nizar Saad BS MSc PhD

Category: Research - Basic

One unmet need in the FSHD field is to find reliable blood biomarkers that correlate with muscle damage which does not rely on muscle biopsies. This biomarker can then be used in clinical trials to assess how well the treatment is working and thereby accelerate its approval. We think that such sensitive blood biomarkers can be found in the extracellular vesicles (EVs) of the plasma. EVs are circular nano-sized vesicles secreted by almost all cells of the body, a portion of which is then released into the bloodstream. EVs function as “vehicles” transporting proteins, RNAs and DNAs, and thus transmitting functional messages from the host cell to the recipient cells. In this way, EVs contribute to the change in the state or function of the recipient cells. Importantly, the contents of EVs extracted from a patient's blood can often reflect the disease state of the patient. However, the EV content of FSHD patients has never been characterized.

In this proposal, we aim to unravel the EV composition in the plasma of FSHD patients. Specifically, we plan to extract EVs from patient blood plasma and profile the proteins and RNAs constituting these EVs. Considering the high variability of symptoms and disease presentation in FSHD patients, we plan to conduct our study using two independent patient cohorts (45 patients in total). We will also analyze plasma EVs from healthy donors (control group) to be able to assign FSHD specific biomarkers. We will correlate the biomarker levels to disease severity, age and sex. In parallel, we will analyze the protein and RNA content of plasma EVs in 20 patients enrolled in a longitudinal study. This will entail analyzing the same patients’ EV contents at three different time points over the span of two years, allowing us to track the levels of potential biomarkers over the progression of the disease.

Altogether, the experiments described in this proposal address the need for identifying and validating minimally invasive, less painful, and more reliable biomarkers which can be used as outcome measures for disease progression, patient selection to clinical trials, and response to therapies.

Note: Mentorship by Dr. Saad.

Note: Possible second year of funding based on first year results.