Superexpression of miR-29c as a potential treatment of skeletal muscular atrophy in cancer-induced caquexia

• Grant number: 19/15795-5
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: August 01, 2020
• End date: April 30, 2021
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: William Jose da Silva
• Grantee: William Jose da Silva
• Company: Mirscience Therapeutics Serviços de Pesquisa e Desenvolvimento Ltda
• CNAE: Atividades de serviços de complementação diagnóstica e terapêutica
• Associated researchers: Lucas Ariel Fernandes da Rocha ; Ricardo Di Lazzaro Filho
• Associated research grant(s): 21/06754-3 - Development of the miR-29c (miR-MT29) for the treatment of skeletal muscle atrophy, AP.PIPE
• Associated scholarship(s): 20/10623-9 - Analysis of the effects of miR-29c overexpression on skeletal muscle in mice with cachexia, BP.TT; 20/09622-8 - Superexpression of miR-29c as a potential treatment of skeletal muscular atrophy in Cancer-induced Caquexia, BP.PIPE

Abstract

The skeletal muscle is the largest tissue of the human body, and is involved in fundamental homeostatic processes such as posture, locomotion and energy balance. The skeletal muscle can modulate its mass and function according to the demands of the environment, leading to conditions known as atrophy and hypertrophy. Atrophy is a condition that reduces muscle mass and function, and contributes to increased mortality, which can be observed in several clinical cases, such as in the elderly, patients in bed rest or cancer. In cancer, a metabolic syndrome called of cachexia, causes a serious and progressive muscular atrophy, which causes the death of a large number of patients with cancer. Several studies have shown that cachexia therapy requires multidisciplinary approaches such as nutritional, pharmacological and physical interventions, but there is no treatment that effectively protects or inhibits the progressive loss of muscle mass and function, which is one of the main consequences of this syndrome. Recently, overexpression of the microRNA-29c in the skeletal muscle of mice has increased muscle mass and strength (hypertrophy), accompanied by an increase in the number of activated myogenic cells and a concomitant reduction of genes related to the atrophic process (patent filed with INPI / SP no. BR 10 2018 067702-0). In this innovation project we contemplate the use of this microRNA-29c as a potential inhibitor of the atrophic process inflicted by cancer-induced cachexia. We will use for this purpose, mouse models of cancer-induced cachexia by the inoculation of C26 tumor cells, then we will overexpress the microRNA-29c by electroporation in the muscle and we will analyze the cellular, molecular and functional effects of this overexpression. In this proposal we want to explore gene therapy by microRNAs as a future therapeutic tool for cancer-induced cachexia. (AU)