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Development of the miR-29c (miR-MT29) for the treatment of skeletal muscle atrophy

Grant number: 21/06754-3
Support type:Research Grants - Innovative Research in Small Business - PIPE
Duration: December 01, 2021 - November 30, 2023
Field of knowledge:Biological Sciences - Biology
Principal researcher:William Jose da Silva
Grantee:William Jose da Silva
Company:Mirscience Therapeutics Serviços de Pesquisa e Desenvolvimento Ltda
CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
Atividades de ensino não especificadas anteriormente
City: São Paulo
Assoc. researchers: Lucas Ariel Fernandes da Rocha ; Ricardo Di Lazzaro Filho
Associated research grant:19/15795-5 - Superexpression of miR-29c as a potential treatment of skeletal muscular atrophy in cancer-induced caquexia, AP.PIPE
Associated scholarship(s):21/13155-9 - Development of the miR-29c (miR-MT29) for the treatment of skeletal muscle atrophy, BP.PIPE

Abstract

Skeletal muscle is the largest tissue in the human body and is involved in fundamental homeostatic processes such as regulation of energy balance, in addition to posture and locomotion. Maintaining the quality of muscle tissue is a key factor for a healthier life and longevity. Muscle atrophy is an adaptive process that reduces muscle mass and function, and in several cases, such as cachexia in cancer and sarcopenia in aging, it directly affects quality of life, increasing mortality. In a recent work, we demonstrated that miR-29c overexpression, using the electroporation gene delivery method, is able to increase the skeletal muscle mass and function of mice, in addition to reducing genes related to muscle atrophy in vivo and in vitro. Furthermore, in our PIPE phase 1 project, we demonstrated that miR-29c overexpression was able to inhibit muscle atrophy in mice with cancer-induced cachexia or with immobilization-induced atrophy. To advance our project with a focus on future clinical studies, we need to develop a molecule based on miR-29c and, in this sense, the challenges of developing and optimizing the molecule for delivery to muscle tissue need to be overcome. In this PIPE phase 2 project proposal, we will develop an oligonucleotide, based on miR-29c, in order to be a future treatment approach for diseases and syndromes involving the loss of skeletal muscle mass. In summary, the steps for this development consist of: selecting in vitro the best oligonucleotide with the modified miR-29c sequence; perform in vivo tests to select the best route of administration, whether intravenous or subcutaneous, in addition to selecting the best dose and verifying the response time; and finally, use the oligonucleotide to treat muscle wasting in mouse models with immobilization-induced atrophy or cancer-induced cachexia. At the end of this PIPE phase 2 project, we hope to be ready for the development of pre-clinical studies, and with that we will have a very important advance in the development of our product. (AU)

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