Development of MT-02: Oligonucleotide Aimed at the Treatment of Sarcopenia

• Grant number: 24/22114-2
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: October 01, 2025
• End date: September 30, 2027
• Field of knowledge: Biological Sciences - Biology
• Principal Investigator: William Jose da Silva
• Grantee: William Jose da Silva
• Associated researchers: André Cruz de Oliveira ; Lucas Ariel Fernandes da Rocha ; Milena Trevisan Pelegrino ; Ricardo Di Lazzaro Filho
• Associated scholarship(s): 25/21874-6 - Molecular Analyses of the Effect of MT-02 in the Treatment of Muscle Atrophy, BP.TT; 25/21290-4 - Evaluation of the in vitro and in vivo efficacy and safety of the oligonucleotide MT-02 for the treatment of sarcopenia, BP.TT

Abstract

The increase in life expectancy has the potential to extend individuals' productive and socially engaged periods. However, this rise in lifespan has not been accompanied by a corresponding addition of healthy years in the population. Aging and chronic diseases, such as obesity, are risk factors that share a common link with sarcopenia, which stands out as a critical limiting factor. Sarcopenia, characterized by the loss of muscle mass (atrophy) and function, significantly impacts individuals' quality of life and autonomy. It is estimated that, in Brazil, by 2060, at least 21 million people will develop sarcopenia, negatively affecting the economy and the national healthcare system.The loss of mobility leads to a need for specialized care, the removal of individuals from the workforce, an increase in depression incidence, chronic diseases such as diabetes, and high mortality rates. Currently, there is no specific and effective therapy for treating muscle atrophy, making the development of a therapeutic solution for the recovery of muscle mass and strength critical. Supported by the accelerated development of RNA-based therapies, we focus on the role of microRNAs in sarcopenia, specifically through the inhibition of miR-29b. The inhibition of this microRNA has been shown to restore muscle mass in aged animals, establishing it as a therapeutic target.This proposal aims to develop an miR-29b inhibitor drug to restore muscle mass and function during sarcopenia. Challenges in this type of therapy include resistance to degradation in the body and targeted delivery to the intended tissue. In this regard, Mirscience Therapeutics specializes in developing technologies to overcome these challenges. Therefore, we aim to design and develop a modified oligonucleotide to optimize stability and targeting to skeletal muscle. Initially, we will develop various oligonucleotide sequences with chemical modifications capable of inhibiting miR-29b. Following in vitro screenings for effectiveness and safety, the most promising compound (MT-02) will be selected for in vivo tests on sarcopenia models. Based on in vivo assays, we will define MT-02's therapeutic potential for sarcopenia treatment, establishing its safety profile, therapeutic dose, treatment frequency, and the stability of its effects over time. This will allow us to gather sufficient data to evaluate the molecule's likelihood of success in pre-IND and clinical trials. (AU)