miRNA Expression Profiling using Nanostring nCounter Technology to Identify Potential Biomarkers in RYR1-RM and Healthy Individuals

Topic:

Clinical Trials

Poster Number: M237

Author(s):

Pooja Varma, BS, National Institute of Nursing Research, NIH, Bethesda, MD, USA, Payam Mohassel, MD, Neuromuscular and Neurogenetic Disorders of Childhood Section, NIH, Bethesda, MD, USA, Joshua J. Todd, PhD, Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorders and Stroke, Clinical Trials Unit, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA, Tokunbor A. Lawal, PhD, National Institute of Nursing Research, NIH, Bethesda, MD, USA

Background:
Rare diseases present significant health inequities and economic burden on affected individuals. RYR1-related myopathies (RYR1-RM) are congenital myopathies caused by pathogenic variations in ryanodine receptor-type 1 gene (RYR1). Associated RYR1-RM symptoms include proximal and facial muscle weakness, myalgia, malignant hyperthermia susceptibility, breathing problems and ophthalmoplegia in severe cases. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that regulate gene expression of target mRNAs. The relative abundance of miRNAs associated with different disease states offers the potential for discovery of novel biomarkers and new biological insights.
Objective: The purpose of this study was to identify relevant miRNAs signatures in RYR1-RM.
Method: Baseline plasma samples were collected from RYR1-RM patients in a Phase 1 trial (NCT04141670), who all have a diagnosis of RYR1-RM (n=6). RNA was extracted from the plasma samples using Qiagen miRNeasySerum/PlasmaAdvanced Kit (#217204). Analysis was performed on all samples using the nCounter Analysis System by NanoString Technologies and then Counter Human v3 miRNA Panel which contains 799 unique miRNA barcodes. Differential expression analysis was performed using Rosalind.
Results: 50 miRNA’s were significantly downregulated and a single microRNA, hsa-mir-4454+has-mir-7975, was found to be significantly upregulated.
Conclusions: Previous studies have reported that miRNAs have been implicated in the widespread control of critical biological processes such as proliferation, differentiation, and apoptosis. Characterizing these potential biomarkers will uncover the important roles they play in the regulation/dysregulation of RYR1. Future works include replicating this assay on more patient samples in order to expand our data set as well as validate the significantly expressed miRNA’s identified in our analysis.