Generation of edited DMD pigs with modifications in Notch3

• Grant number: 24/07915-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 26, 2025
• End date: May 25, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mayana Zatz
• Grantee: Igor Neves Barbosa
• Supervisor: Eckhard Wolf
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Ludwig Maximilian University of Munich (LMU Munich), Germany
• Associated to the scholarship: 23/07376-8 - Assessment of the therapeutic potential of modifications in Notch3 in mdx mice and DMD pigs, BP.DR

Abstract

Duchenne Muscular Dystrophy (DMD) represents a severe and progressive neuromuscular condition, originating from mutations in the DMD gene. These mutations lead to the absence or malfunction of dystrophin, a crucial protein for maintaining the structure of muscle fibers. The deficiency of this protein results in continuous muscle degeneration and strength loss. Although there have been notable advancements in understanding the disease, current therapies, including corticosteroids, gene therapy, and exon-skipping, have been limited in changing the severe trajectory of DMD. These interventions offer some symptom relief but do not significantly improve the life expectancy or quality of life for patients. This reality underscores the vital importance of ongoing research and developments in the field. Our research group's identification of rare cases of DMD with mild manifestations even in the absence of dystrophin suggests the existence of unknown protective mechanisms, paving the way for new therapeutic approaches. Investigating these emerging strategies is crucial in our dedication to developing more effective treatments for DMD and other muscular dystrophies, aiming not only to extend patients' lives but also to substantially improve their quality of life. (AU)