TherApeutic TArgeting of MIrnas for myotonic dystrophy
Project resources: Summary of the project:
Our group previously found two regulatory miRNA molecules (miR-23b and miR-218) that repress expression of MBNL1 and MBNL2. Subsequently, we demonstrated that blocking these miRNAs with antisense oligonucleotides (AONs) antagomiRs (antagomiR-23b and antagomiR-218) improved myotonic dystrophy-like alterations in a mouse model of disease (Cerro-Herreros et al. 2018). Through TATAMI project, (funded by "La Caixa" Banking Foundation under the project code HR17-00268) we aim to design a range of chemically diverse miRNA inhibitory compounds (improved antagomiRs), in partnering with biotech companies, which will be tested in cell and in vitro muscle models to find the optimal efficacy vs. toxicity ratio. Selected candidates will be further analyzed in vivo in two mouse models to assess muscle and central nervous system activity as well as preclinical safety. Finally, the molecular consequences triggered by the best lead compounds will be characterized in human muscle cells in culture.
This is a highly translational project to be executed by a leading edge international consortium with the help of Myotonic Foundation and Spanish Patient Federation ASEM with the main goal of introducing AONs into actual DM1 therapies since recent success with antisense oligonucleotide (AON) drugs offers the current opportunity of precision medicine for this rare disease.
Project updates and our social channels:
New data regarding therapeutic potential of antagomiR-23b has been recently published in Cerro-Herreros et al., 2020
More information about TATAMI in our Vimeo channel: https://vimeo.com/user103005442
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