Pathogenesis and therapy of primary immunodeficiencies

Alessandro Aiuti

Alessandro Aiuti

Location: Settore D, Floor 3, Room 6 and 7

Deputy director clinical research, San Raffaele Telethon Institute for gene therapy (SR-Tiget)
Group leader, Pathogenesis and therapy of primary immunodeficiencies Unit
Head, Clinical Research Unit, SR-Tiget
Full professor, Università Vita Salute San Raffaele
Chief of clinic, Pediatric Immunohematology Unit

Dr. Aiuti has a strong background in immunology and hematology and has been involved since many years in studying the genetics, disease pathogenesis and innovative treatments of several congenital immunological defects (such as ADA-SCID, DADA2, ARPC1B, X-CGD, Wiskott-Aldrich Syndrome, Ataxia Teleangectasia, CVID, DiGeorge Syndrome). He is part of the international COVID-HGE consortium that is studying the genetic and immunological bases of susceptibility to severe COVID-19 disease.

His research on hematopoietic stem cell biology led to the discovery of the first chemokine produced by bone marrow cells inducing migration of human hematopoietic stem progenitor cells (HSPC).  In the past decade, Dr. Aiuti and his group have performed in vivo studies on the dynamics of human gene-corrected HSPCs by clonal tracking and functional studies, demonstrating that hematopoietic reconstitution after gene therapy (GT) occurs in distinct multi-clonal waves, with gene corrected HSCs representing a major contributor to steady state hematopoiesis. Dr. Aiuti has contributed as physician scientist to basic studies, preclinical research and clinical studies to successful clinical application (up to market registration) of HSPC-based gene therapy medicinal products for the treatment of rare genetic diseases of the immune system, inborn errors of metabolism and other blood disorders. Dr. Aiuti has followed the entire development process of gene therapy for ADA-SCID up to EU marketing approval of “Strimvelis”, the first ex vivo gene therapy approved worldwide. Since 2016, Dr. Aiuti is the PI of the HSPC GT trials for Metachromatic Leukodystrophy, which demonstrated safety and clinical efficacy in preventing or halting disease progression in the majority of patients and has  achieved EU market approval in 2020 as “Libmeldy” (licensed to Orchard Therapeutics). The approach of HSPC GT based on enzyme overexpression and cross-correction has been recently successfully applied to Mucopolysaccharidosis type I and will be expanded to other lysosomal storage disorders.

Dr. Aiuti is author of more than 230 publications in international scientific peer-review journals and contributed 8 book chapters. He gave more than 100 lectures as invited speaker and abstract presentations to national and international congresses in the last 5 years. He is Member (representing clinicians) of the Committee for Advanced Therapies (CAT) of the European Medicines Agency (EMA). He is board member of IPINET and ESGCT, member of: the Inborn Errors Working Party (IEWP), ASGCT (International Committee and Global Outreach Committee), European Reference Network (ERN) on Rare Immunodeficiency, Autoinflammatory and Autoimmune Diseases Network (RITA). He serves as reviewer for: Nature, NEJM, Blood, Hum Gen Ther, Haematologica, JACI, Mol Ther, Frontiers .

Dr. Aiuti’s research is funded by international and national agencies including the European Union, Telethon Foundation, the Italian Ministry of Education University and Research, Italian Ministry of Health, Else Kroener Fresenius Foundation.