Molecular markers of clinical severity in Becker muscular dystrophy


Preclinical Trial Design & Biomarker Development

Poster Number: 145


Utkarsh Dang, PhD, Michael Ziemba, Marissa Barbieri, Runia Roy, Kevin Thapa, Alan Russell, PhD, Ben Barthel, Eric Hoffman, PhD


1. Binghamton University, 6. Edgewise Therapeutics, 8. Binghamton University

Background: Extensive clinical variability has been observed in Becker muscular dystrophy (BMD), both in time of first symptom onset and progression. Understanding causes behind this variable phenotype is key for clinical trials and more biomarker and outcome studies are needed for identification of drug targets and biomarker-focused clinical trials.

Objectives: To define molecular markers of clinical severity in Becker muscular dystrophy.

Approach: The Binghamton Becker Study was conducted at Binghamton University and recruited 54 volunteers with DNA-confirmed Becker muscular dystrophy (BMD) 6 years of age or older. Data was collected through an innovative 'remote' clinical study design. Recruitment was via stake holder foundations, informed consent via phone, and blood and urine collection using a mobile phlebotomist at patient home. NeuroQL and other PROs obtained data about depression, fatigue, anxiety, and lower and upper extremity mobility.

Results:  There was a broad range of clinical severity across all age groups; ~15% of BMD patients reported taking corticosteroids. An index of current clinical severity was constructed based off of the NeuroQOL questionnaires. Serum biomarker data was obtained on all patients (muscle enzymes, cytokines, microRNA).  Principal component analysis of the biomarkers and clinical data (age, severity, mutation) was run to understand common sources of variation in the largest direction of variance from these data.  Based on multivariate data analyses, biomarkers were grouped, e.g., into reflecting muscle leakage, inflammation, etc.

Conclusions: This pilot study defined severity-associated biomarkers using a cross-sectional innovative design utilizing patient-reported outcomes and mobile-collected biosamples. This may lead to a better understanding of progression in Becker muscular dystrophy, identifying drug targets, and biomarker-focused clinical trials of therapeutic agents in BMD.