Integrated assessment of the therapeutic potential of antimiR. Credit: Scientific advances (2024). DOI: 10.1126/sciadv.adn6525
A team of researchers has identified a promising antimiR-based therapy to treat myotonic dystrophy type 1 (DM1), a complex genetic disease caused by an abnormally high number of CTG repeats (a specific type of RNA sequence) in the DMPK gene. The results of their research have just been published in Scientific advances.
The work was carried out by researchers from the Human Translational Genomics Group of the Instituto de Investigación Sanitaria de INCLIVA-Universitat de València (UV), led by Dr. Rubén Artero, in collaboration with the company Arthex Biotech, resulting from the results of research from INCLIVA and UV, the Neuromuscular Research Group of Badalona (GRENBA) of the German Research Institute Trias i Pujol (IGTP), the Health Research Institute Biogipuzkoa and the Health Research Institute Hospital La Fe.
The study, carried out on eight muscle cell lines directly derived from biopsies of patients with DM1, demonstrated that blocking small regulatory RNAs, called microRNAs, via perfectly complementary molecules, called antimiRs, increases the expression of the essential protein MBNL1, usually repressed. in DM1, causing muscle dysfunction.
DM1 arises due to a reduction in MBNL1 protein, contributing to a wide range of clinical symptoms associated with the disease. The study showed that untreated cells from DM1 patients had elevated levels of miR-23b and miR-218, microRNAs that repress MBNL1.
In an encouraging development, treatments with antimiRs not only increased MBNL1 levels, but also significantly improved the functions normally carried out by this protein and muscle cells. Surprisingly, the therapy also reduced the number of disease-causing expander molecules, preventing the formation of accumulations of expanded molecules and MBNL1 protein, known as “ribonuclear foci.”
The best-performing antimiR was able to reverse 68% of dysregulated genes, offering hope for broader therapeutic benefits in DM1 patients, regardless of intrinsic genetic variations among the cell lines used.
Dr Gisela Nogales, head of the GRENBA group at IGTP and author of the study, explains: “Thanks to the collaboration of patients in this work, several cellular models derived from them have been studied, showing that antimiRs could have therapeutic potential in patients. with different degrees of severity of DM1.
Dr. Rubén Artero, corresponding author of the study, adds that “this study demonstrated the great potential of antimiRs to treat different forms of myotonic dystrophy type 1 by releasing the MBNL1 protein and improving its production.”
Dr. Estefanía Cerro, first author of the article, notes: “If clinical trials prove successful, antimiRs could become a viable therapeutic strategy for DM1, offering hope to patients affected by this debilitating disease. »
This advancement highlights the importance of continued research into RNA-targeted therapies to treat genetic disorders like DM1, which, until now, lack effective treatment options.
More information:
Estefanía Cerro-Herreros et al, AntimiR treatment corrects defects in primary myotonic dystrophy cells across multiple CTG repeat expansions with a dual mechanism of action, Scientific advances (2024). DOI: 10.1126/sciadv.adn6525
Provided by the German Research Institute Trias i Pujol
Quote: New study reveals promising therapy that blocks microRNAs to treat myotonic dystrophy type 1 (October 15, 2024) retrieved October 15, 2024 from
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