Researchers at Duke University have developed a new method to study and test treatments for rare muscle disorders known as dysferlinopathy or limb girdle muscular dystrophies 2B (LGMD2B). They have successfully grown functional 3D muscle tissue in the lab from stem cells to mimic patient symptoms and responses to treatment.
A recent study published in the journal Advanced Science has unveiled some of the biological mechanisms behind the mobility loss seen in LGMD2B. The research suggests that a combination of existing treatments could potentially help alleviate the severe symptoms of the disease.
LGMD2B is a rare condition affecting approximately eight individuals per million globally. Unlike the more common Duchenne muscular dystrophy, LGMD2B impacts both men and women, typically manifesting in late teens or early twenties and often leading to reliance on wheelchairs due to severe weakness in the legs and shoulders.
The disease, caused by a genetic defect, impairs the production of a critical protein called dysferlin, resulting in various complications such as muscle membrane damage, disrupted calcium balance for muscle function, and altered cellular metabolism. Affected muscles initially accumulate fat before deteriorating and being replaced by fat cells, a phenomenon that puzzles researchers.
Professor Nenad Bursac, a biomedical engineering expert at Duke, highlights the rarity of this fat accumulation within muscle fibers in LGMD2B, sparking curiosity in the scientific community. Unlike mice models often used for research, LGMD2B patients exhibit more severe symptoms, posing challenges in studying the disease progression.
To overcome these hurdles, Bursac and his team leveraged a muscle-growing technique they had been refining for years. By utilizing induced pluripotent stem cells from LGMD patients, the researchers generated muscle fibers to replicate disease characteristics in a controlled setting.
The lab-grown muscles exhibited similar issues observed in patients, showcasing deficiencies in calcium handling and a lack of muscle repair due to dysferlin deficiency. The study also revealed insights into the muscle-specific aspects of LGMD2B.
Furthermore, the researchers tested two potential drug candidates for LGMD2B treatment, dantrolene and vamorolone, which showed promising results in preventing calcium leaks and aiding muscle repair, although challenges in fat metabolism remain unresolved.
Future research aims to introduce immune and fat cells into the muscle model to better understand disease complexities and develop more comprehensive treatment strategies.
This study was supported by the National Institutes of Health and the Jain Foundation.
