A study recently published in Science Translational Medicine found that GLPG1972, a drug that inhibits the enzyme ADAMTS-5, improves muscle function and reduces inflammation in a mouse model of Duchenne muscular dystrophy (DMD).
“These findings position ADAMTS-5 inhibition with GLPG1972 for further study as a disease-modifying strategy for DMD that may achieve both anti-inflammatory and antifibrotic effects on muscle,” the authors wrote.
ADAMTS-5 (also called “A disintegrin and metalloproteinase with thrombospondin motifs 5”), a protein that promotes the degradation of cartilage, is often overexpressed in patients with DMD. The enzyme plays a role in inflammatory responses throughout the body, and previous studies have suggested that targeting ADAMTS-5 overexpression may support muscle strength in DMD.
GLPG1972 is a small molecule drug that blocks the activity ADAMTS-5. In a clinical trial of patients with osteoarthritis, GLPG1972 was found to be safe, although it did not significantly reduce cartilage loss. In this study, the authors treated a mouse model of DMD with GLPG1972 and analyzed the muscle tissue for signs of damage.
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Results showed that ADAMTS-5 triggers an immune response in areas of the muscle tissue affected by fibrosis and inflammation. Treatment with GLPG1972 was found to reduce the inflammation and fibrosis while also alleviating muscle pathology.
In terms of muscle function, GLPG1972 significantly enhanced grip strength, diaphragm function and the contractile ability of several muscles.
Treatment with prednisolone, a glucocorticoid, and GLPG1972 together improved muscle fiber size more than either therapy alone, suggesting a potential benefit of combination therapy. However, combination treatment significantly decreased bone volume, while GLPG1972 alone did not.
Osteoporosis is one of several side effects of treatment with glucocorticoids. Nevertheless, this class of therapy remains the current standard of care for patients with DMD. The authors argue, therefore, that there is a need to develop therapeutics, potentially including GLPG1972, that improve muscle performance without serious adverse effects.
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