Objective The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs). LSDs are fatal diseases of childhood occurring in 1:5000-7000 live births; in >50% of the cases, LSD patients experience a severe neurological deterioration. Most LSDs with central nervous system (CNS) involvement lack a curative treatment. Hematopoietic cell transplantation (HCT) form healthy donors is applied to LSD patients in order to repopulate the recipient myeloid compartment, including CNS microglia, with donor-derived cells expressing the defective functional hydrolase. Over the past three decades, about 1000 HCTs have been performed for patients with LSDs with a variable benefit exerted on the CNS. The positive results obtained in Hurler syndrome and few other LSDs and the benefit observed in our on going Phase I/II clinical trial of HSC gene therapy for the demyelinating LSD metachromatic leukodystrophy indicate that migration of the transplanted Hematopoietic Stem Cells (HSCs)/their progeny into the affected human brain occurs. However, timing of resident CNS macrophages and microglia replacement by the transplanted cell progeny is frequently too slow for clinical benefit due to the rapid progression of the primary neurological disease, particularly in the most aggressive LSD variants. Thus, a deep understanding of the modalities, time course and factors that affect this phenomenon might allow enhancing clinical benefit of HSC-based approaches for treating the LSD brain disease. The proposed work, combining basic and innovative preclinical research with the information derived from a pioneering clinical experience, will generate the basis for designing more efficacious and safer transplant approaches for these fatal diseases. Fields of science natural sciencesbiological sciencesneurobiologymedical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinetransplantation Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-CG-2013-LS7 - ERC Consolidator Grant - Diagnostic Tools, Therapies and Public Health Call for proposal ERC-2013-CoG See other projects for this call Funding Scheme ERC-CG - ERC Consolidator Grants Host institution OSPEDALE SAN RAFFAELE SRL EU contribution € 1 751 147,00 Address VIA OLGETTINA 60 20132 Milano Italy See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Principal investigator Alessandra Biffi (Dr.) Administrative Contact Maria Rosa Pedrazzi (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all OSPEDALE SAN RAFFAELE SRL Italy EU contribution € 1 751 147,00 Address VIA OLGETTINA 60 20132 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Principal investigator Alessandra Biffi (Dr.) Administrative Contact Maria Rosa Pedrazzi (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
