Gene therapy with 7ND mutant protein for murine limb ischemia

• Grant number: 16/19390-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2017
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Sang Won Han
• Grantee: Gabriel Palermo Ruiz
• Host Institution: Centro de Terapia Celular e Molecular. Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Peripheral arterial disease (PAD) has a prevalence of 10% in population, and the people over 70 year-old the prevalence can reach 20%. The main cause of PAD is atherosclerosis, which leads to obstruction of vessels, generating ischemia and chronic critical limb ischemia (ICC) in long-term. The ICC compromises the physical and functional integrity of the patient and may lead to limb loss and even death. For tissue regeneration and repair, the efficient vessel formation is crucial. It has been seen that prolonged activity of M1 macrophages is related to lower angiogenic and tissue regeneration rates, consequently, inhibition of M1 chemotaxis to the ischemic site can favor the migration of the pro-resolutive M2 macrophage. The aim of this project is to prove the above hypothesis in the limb ischemia using 7ND gene, a mutant of chemokine CCL2, in order to inhibit M1 chemotaxis by competition with CCR2 in murine model. By this gene therapy, it is expected improvement of wound healing, increase of arteriogenesis and angiogenesis and, consequently, better blood perfusion. (AU)