Investigating cellular homeostatic mechanisms underlying rare and prevalent neurodegenerative diseases using human induced pluripotent stem cells

• Grant number: 17/08000-0
• Support type: Regular Research Grants
• Duration: September 01, 2018 - August 31, 2020
• Field of knowledge: Interdisciplinary Subjects
• Cooperation agreement: University of Birmingham
• Principal Investigator: Tatiana Rosado Rosenstock
• Grantee: Tatiana Rosado Rosenstock
• Principal investigator abroad: Sovan Sarkar
• Institution abroad: University of Birmingham, England
• Home Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil
• Assoc. researchers: Carl Ward ; Isaias Glezer ; Malgorzata Zatyka ; Timothy Barrett

Abstract

Most rare and common neurodegenerative disorders have no effective treatment or cure. One reason is the lack of reliable cell or animal models that consistently replicate the disease phenotypes. The outlook for new treatments has become more hopeful with the recognition that many of these diseases involve perturbations of a few key cellular pathways. Two major contributing pathways, which are defects in autophagy and mitochondrial function, underlie many rare forms of neurodegeneration as well as more prevalent neurodegenerative diseases. Our overarching goal therefore is to develop disease-affected human cellular platforms using human induced pluripotent stem cell (hiPSC)-based disease models to investigate dysfunction in autophagy and mitochondria (shared across rare childhood and prevalent late-onset neurodegenerative diseases), that will allow identification of new therapeutic interventions and enable drug discovery by targeting the common disease mechanisms. The project will focus on two neurodegenerative conditions, Wolfram syndrome (rare childhood neurodegenerative disease) and Amyotrophic lateral sclerosis (common late-onset neurodegenerative disease), chosen because of local expertise in these areas. In future, this proof-of-concept proposal will facilitate the extension of the research paradigm and technology to other diseases and processes for a widespread biomedical impact. Of strategic relevance, the project will lead to institutional links between Birmingham, Sao Paulo and Nottingham, as well as support the establishment of a Birmingham stem cell facility for rare diseases and the foundation of human stem cell infrastructure in Sao Paulo for future cell-based or drug therapies. (AU)