The slow-release adiponectin analogue ALY688-SR modifies early-stage disease development in the D2.mdx mouse model of Duchenne muscular dystrophy
Am J Physiol Cell Physiol. 2023 Dec 25. doi: 10.1152/ajpcell.00638.2023. Online ahead of print.ABSTRACTFibrosis is associated with respiratory and limb muscle atrophy in Duchenne muscular dystrophy (DMD). Current standard of care partially delays the progression of this myopathy but there remains an unmet need to develop additional therapies. Adiponectin receptor agonism has emerged as a possible therapeutic target to lower inflammation and improve metabolism in mdx mouse models of DMD but the degree to which fibrosis and atrophy are prevented remain unknown. Here, we demonstrate that the recently developed slow-release peptidomimetic adiponectin analogue, ALY688-SR, remodels the diaphragm of D2.mdx mice treated from days 7-28 of age during early stages of disease. ALY688-SR also lowered IL-6mRNA but increased IL-6 and TGF-β1 protein contents in diaphragm, suggesting dynamic inflammatory remodeling. ALY688-SR alleviated mitochondrial redox stress by decreasing complex I-stimulated H2O2 emission. Treatment also lowered in vitro diaphragm force production in diaphragm suggesting a complex relationship between adiponectin receptor activity, muscle remodeling and force generating properties during the very early stages of disease progression in D2.mdx mice. In tibialis anterior, the modest fibrosis at this young age was not altered by treatment, and atrophy was not apparent at this young age. These results demonstrate that short-term treatment of ALY688-SR in young D2. mdx mice ...
Source: Am J Physiol Cell Ph... - Category: Cytology Authors: Catherine A Bellissimo Shivam Gandhi Laura N Castellani Mayoorey Murugathasan Luca J Delfinis Arshdeep Thuhan Madison C Garibotti Yeji Seo Irena A Rebalka Henry H Hsu Gary Sweeney Thomas J Hawke Ali A Abdul-Sater Christopher G R Perry Source Type: research
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