A new preclinical study has shown that reducing the protein HDAC11 could slow muscle degeneration in Duchenne muscular dystrophy, providing a potential target for future therapies.
A preclinical study led by the Germans Trias i Pujol Research Institute (IGTP), in collaboration with the Institut de Myologie and the Sant Pau Research Institute, has highlighted the role of the protein HDAC11 in Duchenne muscular dystrophy (DMD) and its potential as a target for future therapies.
Understanding Duchenne muscular dystrophy
DMD is a severe genetic condition that progressively deteriorates the muscles. It usually manifests in childhood and worsens steadily throughout life. Currently, there is no cure, and treatment options are limited, focusing mainly on slowing disease progression and improving patients’ quality of life.
DMD is a severe genetic condition that progressively deteriorates the muscles.
The Badalona Neuromuscular Research Group (GRENBA) at IGTP has been investigating the molecular mechanisms behind neuromuscular disorders for several years. Their goal is to identify strategies that could help preserve muscle function. In earlier studies, the team had explored the role of HDAC11 in muscle loss associated with ageing and sarcopenia. The latest research develops this work, showing that HDAC11 also plays a significant role in severe neuromuscular diseases such as DMD.
Collaboration and experimental approach
For this study, researchers worked with the Heart Failure and Cardiac Regeneration Group (ICREC), the Institut de Myologie and the Sant Pau Research Institute to examine the effects of total or partial reduction of HDAC11 in a murine model of DMD. Experiments were conducted at the Comparative Medicine and Bioimage Centre of Catalonia (CMCiB), a strategic IGTP facility, which provided specialised technical support.
Through a combination of histological, functional and molecular analyses, the team observed notable improvements in dystrophic mice. Muscle damage, fibrosis and chronic inflammation were reduced, while muscle strength and endurance improved in both young and older animals. These changes contributed to better preservation of muscle structure and slowed key processes involved in disease progression. The study demonstrates for the first time that genetic reduction of HDAC11 has a broad impact on the dystrophic phenotype in an experimental DMD model.
Impact on fibro-adipogenic progenitor cells
The research also focused on fibro-adipogenic progenitor cells, which play a role in replacing muscle tissue with fibrotic tissue. In the absence of HDAC11, these cells displayed a reduced capacity to generate fibrosis and a greater tendency to undergo apoptosis. This limits their accumulation in dystrophic muscles and provides an additional mechanism by which HDAC11 reduction could help protect muscle tissue.
Potential for future therapies
"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 GRENBA and first author of the article.
The findings offer a new area of exploration for future DMD research.
The researchers emphasise that this is a preclinical study and more research will be required to determine whether selective inhibition of this protein could translate into safe and effective therapeutic strategies in humans.
The findings offer a new area of exploration for future DMD research and highlight HDAC11 as a potential focus for therapies aimed at slowing the progression of the disease.
