Protein and miRNA biomarker candidates for facioscapulohumeral muscular dystrophy


Preclinical Trial Design & Biomarker Development

Poster Number: 147


Aiping Zhang, PhD, Christopher Heier, PhD, Alyson Fiorillo, PhD, Christopher B. Tully, PhD, Aswini Panigrahi, PhD, Heather Gordish-Dressman, Sachchida Nand Pandey, Jean Mah, Yi-Wen Chen, PhD


1. Children's National Hospital, 2. Children's National Hospital, 3. Children's National Hospital, 4. Children's National Medical Center, 6. Children’s National Medical Center, Washington, DC, USA, 9. Children's Research Institute (CNMC)

Background: Circulating biomarkers can be used to evaluate disease states and responses to therapeutic interventions. Protein and miRNA in blood samples are biomarker candidates what can be evaluated with easy, accurate and less invasive means.
Objective: To identify protein and miRNA biomarker candidates using omics approaches.

Approach: Blood samples from a clinically well characterized cohort of individuals with early-onset FSHD were used for the study. For protein biomarkers, we removed the top 12 most abundant proteins before obtaining the protein profiles using the Q Exactive HF mass spectrometer (22 FSDH and 14 controls). miRNA profiling was conducted using TaqMan Array Human MicroRNA assays (28 FSHD and 16 controls). ELISA and qRT-PCR were used to validate data. In addition, mouse sera from FLExDUX4 mice were studied to validate miRNA changes.

Results: We identified 28 proteins and 14 miRNAs that were differentially expressed between FSHD and controls; 13 proteins and 3 miRNAs correlated with disease severity. Several identified proteins and miRNAs were reported to be altered in other neuromuscular diseases. We validated several protein and miRNA candidates using ELISA and qRT-PCR assay. Overlap between human and mouse miRNA was identified.

Conclusion: The identified proteins and miRNAs will be further validated and prioritized to be used as biomarkers for therapeutic trials.