Translating Microarray Findings from GRMD to Identify Biomarkers in DMD

This study focuses on translating microarray findings from golden retriever muscular dystrophy (GRMD) to identify biomarkers that could reflect cardiac and skeletal muscle function in Duchenne muscular dystrophy (DMD) patients. Since DMD affects both cardiac and skeletal muscle function, identifying molecular differences between these tissues can help predict disease progression. The research utilized GRMD models, which closely mimic DMD in humans, and studied gene expression in the left ventricle (LV) and medial head of the gastrocnemius (MHG) muscle at different ages to understand tissue-specific disease mechanisms.

Key Biomarkers: Brain-Derived Neurotrophic Factor (BDNF) & Osteopontin (SPP1)

• BDNF (Brain-Derived Neurotrophic Factor): - Found to be elevated in the cardiac muscle of younger GRMD dogs but was unaltered in skeletal muscle. - In human DMD patients, higher circulating BDNF levels were associated with better cardiac function.
• SPP1 (Osteopontin): - Increased in skeletal muscle but not in cardiac muscle at younger ages in GRMD dogs. - In DMD patients, higher SPP1 levels correlated with skeletal muscle function, but not with cardiac dysfunction.

Validation in Human DMD Patients

The study validated these biomarkers in human DMD patients and found that serum BDNF levels were significantly higher in DMD patients compared to healthy controls. Moreover, BDNF levels were inversely correlated with the extent of myocardial fibrosis, further supporting its potential as a marker for cardiac disease progression. SPP1, on the other hand, correlated well with muscle function but not with cardiac dysfunction, indicating its specificity for skeletal muscle injury.

Conclusion

• BDNF and SPP1 are promising biomarkers for assessing cardiac and skeletal muscle health in DMD.
• These findings highlight the importance of age and tissue specificity in DMD progression.
• Using GRMD as a model enhances our ability to translate preclinical research to human patients.

Future Directions

Further clinical trials are needed to evaluate the long-term reliability of BDNF and SPP1 as biomarkers for DMD progression. Additionally, new therapeutic strategies could focus on modulating BDNF and SPP1 pathways to improve muscle function.