An innovative hematopoietic stem cell gene therapy approach benefits CLN1 disease in the mouse model

ABSTRACT: Hematopoietic stem and progenitor cells (HSPCs) can establish a long-lasting microglia-like progeny in the brain of properly myeloablated hosts. We exploited this approach to treat the severe CLN1 neurodegenerative disorder, which is the most aggressive form of neuronal ceroid lipofuscinoses, due to palmitoyl-protein thioesterase-1(PPT1) deficiency. We here provide first evidence that: i) transplantation of wild-type HSPCs exerts partial but long-lasting mitigation of CLN1-symptoms; ii) transplantation of HSPCs over-expressing hPPT1 by lentiviral gene transfer enhances the therapeutic benefit of HSPCs transplant, with first demonstration of such a dose-effect benefit for a purely neurodegenerative condition like CLN1-disease; iii) transplantation of hPPT1 over-expressing HSPCs by a novel i

SUBMITTER: Prof. Marco Peviani 

PROVIDER: S-SCDT-10_15252-EMMM_202215968 | biostudies-other |

REPOSITORIES: biostudies-other