Assessment of the therapeutic potential of modifications in Notch3 in mdx mice and DMD pigs

• Grant number: 23/07376-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2024
• Status: Discontinued
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mayana Zatz
• Grantee: Igor Neves Barbosa
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center, AP.CEPID
• Associated scholarship(s): 24/07915-9 - Generation of edited DMD pigs with modifications in Notch3, BE.EP.DR

Abstract

Duchenne Muscular Dystrophy (DMD) is a severe and progressive neuromuscular disorder caused by mutations in the DMD gene, which lead to the absence or dysfunction of dystrophin protein. This protein plays a crucial role in maintaining the structural integrity of muscle fibers, and its deficiency results in progressive muscle degeneration and weakness. Despite significant advances in our understanding of the pathophysiology of DMD, current therapeutic approaches have largely been ineffective in altering the devastating course of the disease. These strategies, including corticosteroid therapy, gene therapy, and exon-skipping, have provided some symptomatic relief - if at all, but have not fundamentally changed the life expectancy or quality of life of DMD patients. This underscores the urgent need for ongoing research and development in this field. The discovery by our research group of rare cases of DMD with mild phenotypes, despite the absence of dystrophin, underlines the potential for unknown protective mechanisms that could be utilized for new therapeutic approaches. The pursuit of these new strategies is of paramount importance in our ongoing efforts to develop effective treatments for DMD and other muscular dystrophies. The goal is not only to prolong the life of the affected individuals, but also to significantly improve their quality of life.