A preclinical study has identified a potential new therapeutic target for Duchenne muscular dystrophy (DMD), a severe genetic disorder causing progressive muscle degeneration. Researchers found that reducing levels of the protein HDAC11 in a mouse model of DMD lessened muscle damage, fibrosis, and inflammation, leading to improved muscle function.
The study, led by the Germans Trias i Pujol Research Institute (IGTP) in Badalona, Spain, in collaboration with the Institut de Myologie and the Sant Pau Research Institute, offers a promising avenue for developing treatments to slow the progression of this devastating disease. Currently, there is no cure for DMD, and existing treatments primarily focus on managing symptoms and improving quality of life.
Researchers focused on HDAC11, a histone deacetylase enzyme known to regulate gene expression. Their experiments involved examining the effects of both complete and partial reduction of HDAC11 in mice with a genetic mutation mirroring DMD. The work was conducted at the Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), which provided specialized technical support, according to a report from Life Technology.
The results, recently published in the journal Life Sciences, demonstrated significant improvements in the dystrophic mice. Muscle damage and the formation of fibrotic tissue – scar tissue that replaces muscle – were reduced. Chronic inflammation, a hallmark of DMD, too decreased. Importantly, these benefits were observed in both young and older animals, suggesting a potential therapeutic window across different stages of the disease.
Further investigation revealed the impact of HDAC11 reduction on fibro-adipogenic progenitor (FAP) cells. These cells contribute to the replacement of muscle tissue with fibrotic tissue. The study found that, in the absence of HDAC11, FAPs exhibited reduced capacity for fibrosis and a greater tendency to undergo programmed cell death, or apoptosis. This limits their expansion within the damaged muscle, offering another mechanism by which reducing HDAC11 levels could protect muscle tissue.
Single-cell RNA sequencing data revealed distinct subpopulations of FAPs, differing between genotypes, and aligned with the observed reduction in inflammation, suggesting changes in FAP plasticity, according to the study abstract published in PubMed.
“The fact that partial reduction of HDAC11 already shows beneficial effects in the DMD model reinforces the biological relevance of this protein in the disease and opens the door to exploring more specific therapeutic strategies,” said Renato Odria, a researcher at IGTP’s Badalona Neuromuscular Research Group (GRENBA) and first author of the article.
Researchers caution that this is a preclinical study and further research is necessary to determine whether inhibiting HDAC11 can be translated into safe and effective therapies for humans. The study, as reported by Medical Xpress, represents a crucial step in identifying potential new targets for DMD treatment.
