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 50 volunteers with DNA-confirmed Becker muscular dystrophy (BMD) 6 years of age or older. Recruitment of volunteers was via stake holder foundations and social media outlets. Data was collected through an innovative 'remote' clinical study design, 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: Serum biomarker data was generated (muscle leakage enzymes, cytokines, microRNAs) while an index of current clinical severity was constructed based off of the NeuroQOL questionnaires. In 47 mutation-confirmed BMD subjects with both clinical severity and biomarker measurements, there was a broad range of clinical severity across all age groups. The most common deletion mutations were exon ∆45-48 (19%), and ∆45-47 (15%) and ~19% of BMD patients reported taking corticosteroids, and 66% were ambulatory. Principal component analysis of the biomarkers and clinical data (age and severity) was run to understand the structure of their relationship and identified variables that dominate the largest sources of variation as well as mutation groups that are more homogenous than others.
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.