
The results of the research have just been published in ’Science Advances’, the prestigious open access multidisciplinary journal of the American Association for the Advancement of Science (AAAS).
The study, performed on eight muscle cell lines directly derived from biopsies of patients with DM1, showed that blocking small regulatory RNAs, called microRNAs, by perfectly complementary molecules known as anti-miRs, increases the expression of the essential protein MBNL1, which is often repressed in DM1, causing muscle dysfunction.
AntimiRs are molecules that block the action of microRNAs, which are small molecules that regulate how proteins are made in cells. Normally, microRNAs bind to messenger RNAs (mRNAs), which are the instructions that cells use to make proteins. By binding, microRNAs can prevent the production of a protein or reduce its amount.
DM1 is caused by a decrease in the MBNL1 protein, which contributes to a wide spectrum of clinical symptoms associated with the disease. The present 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 anti-miRs not only increased MBNL1 levels but also significantly improved the functions normally performed by this protein and improved muscle cell function. Surprisingly, the therapy also reduced the amount of molecules with the expansions responsible for the disease, preventing the training of clumps of MBNL1 expansions and protein, known as ’ribonuclear foci’ training The ’best’ antimiR was able to reverse 68% of the deregulated genes, offering hope for broader therapeutic benefits in patients with DM1, regardless of intrinsic genetic variations between the cell lines used.
’This study has shown the great potential of antimiRs to treat different forms of myotonic dystrophy type 1 by releasing the MBNL1 protein and improving its production,’ according to Universitat de València full-time university professor Rubén Artero, corresponding author of the study, who adds: ’If clinical studies are positive, antimiRs may become a viable therapeutic strategy for DM1, offering hope to patients affected by this debilitating disease.
This breakthrough underscores the importance of continuing research into targeted RNA therapies to treat genetic disorders such as DM1, which until now have lacked effective treatment options.
About Myotonic Dystrophy type 1 DM1 is a rare genetic disease currently without effective treatment, affecting approximately 1 in 8,000 people in the population. The disease characteristically affects multiple systems and organs, is progressive and can appear at any time of life. Moreover, it manifests itself earlier and is more severe when transmitted to offspring.
DM1 mainly affects the muscles of the limbs, causing weakness and atrophy, which compromises mobility, as well as affecting cognitive functions and causing cardiac arrhythmias, among many other symptoms.