New Treatment Strategy for Rare Disease Dutsenic Muscle Dystrophy...EZH2 inhibitor + steroid effective in combination
Mar 20, 2025
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Professor Chae Jong-hee of the Department of Clinical Genomics Medicine at Seoul National University Hospital and Professor Choi Moo-rim of the Department of Medicine at Seoul National University (first author: Jeon Eun-young and Park Integrated Course Student) announced the results of a study on the 20th that analyzed the muscle tissue of Dusen's muscular dystrophy patients and animal models to find that hyperactivation of the EZH2 gene is a key mechanism for inducing muscle fibrosis and inflammatory reactions, and suggested the possibility of new treatments to suppress it.
Dutsenic muscular dystrophy is a hereditary rare disease in which the muscle gradually weakens and fibrosis progresses due to mutations in the DMD gene. Over time, the patient may lose motor capacity, leading to decreased cardiac and respiratory function. The number of patients in Korea is estimated to be about 2,000, mainly in boys. Currently, steroids, a representative treatment, have the effect of relieving inflammation, but long-term use has side effects such as muscle fibrosis, growth disorders, and weight gain, so there were therapeutic limitations.
To overcome these limitations, the research team paid attention to the 'EZH2 gene', which regulates cell proliferation and differentiation. The EZH2 gene is known to play a role in regulating cell growth and differentiation, but when overactivated, it interferes with muscle regeneration and promotes fibrosis. The research team established a hypothesis that inhibiting the activity of the EZH2 gene could improve muscle function and conducted research to verify it.
The research team precisely analyzed the expression level and muscle fibrosis mechanism of the EZH2 gene by performing single-nuclear transcriptome analysis and spatial transcriptome analysis on muscle tissue from Dusen muscle dystrophy patients, relatively mild Becker muscle dystrophy patients, and normal controls. In addition, the same analysis was performed in the Dusenomycotrophic animal model and compared with human patient samples.
Analysis revealed that hyperactivation of the EZH2 gene in patients with Dusenomyodystrophy and in animal models is directly associated with muscle fibrosis and inflammatory responses.
In addition, the effects of changes in muscle tissue and muscle strength recovery were evaluated after administration of EZH2 inhibitors (GSK126, tazemetostat) alone or co-administration with steroids (deflazacort) using the Dusen muscle dystrophy animal model (D2-mdx mice).
As a result of the experiment, muscle fibrosis decreased, muscle fiber size increased, and recovered to a form similar to normal muscle in the group administered with EZH2 inhibitor alone. In addition, compared to the steroid-only group, it was confirmed that the fibrosis of muscle tissue decreased in the group administered with the EZH2 inhibitor, and the strength test showed a significant increase in muscle strength.
The research team emphasized that this study is an important study that demonstrates that EZH2 inhibitors can promote muscle regeneration and improve muscle strength while minimizing the side effects of steroid treatment, suggesting new possibilities for treatment of Duchene muscle dystrophy. In particular, it is of great significance in that it has provided scientific evidence that treatment strategies with EZH2 inhibitors can increase the effectiveness of treatment for DMD, a rare disease.
Professor Chae Jong-hee (Department of Clinical Genomics and Medicine at Seoul National University Hospital) said, `Although research on the treatment of Duchene muscular dystrophy is being actively conducted, there are not many clinically commercialized treatments yet.' `We look forward to discovering new substances that increase the effectiveness of steroid treatment through this study and taking a step forward in patient treatment through follow-up studies in the future.'
Professor Murim Choi (Department of Medicine, Seoul National University of Medicine) said, `In this study, we conducted a study using patient and animal models to understand the mechanisms by which Dutsenic muscular dystrophy occurs and to find genetic targets that can contribute to patient treatment"The results of this study have been patented, and further research will allow us to expect the clinical effects of EZH2 inhibitors."
Eunyoung Jeon (first author) confirmed that drugs that inhibit the EZH2 gene can reduce muscle weakness and fibrosis while maintaining steroid immunosuppressive effects"It has the potential to be used not only for muscle diseases but also for various diseases that require inflammatory control, and will contribute to the development of treatments based on precision medicine."
The study was carried out with the support of Lee Kun-hee's project to overcome childhood cancer and rare diseases and the Korea Research Foundation, and was published in the latest issue of the international journal Science Advances (IF: 13.6).
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This article was translated by Naver AI translator.
