Descrizione del progetto
Trattamento delle malattie cerebrali basato sulle microglia
Le microglia sono cellule che risiedono nel cervello e sono coinvolte nel mantenimento della salute del cervello e nella modulazione dell’infiammazione. Le microglia disfunzionali sono state collegate a disturbi neurologici, attestandosi come l’obiettivo primario per la terapia. Le microglia sono in grado di autorinnovarsi, offrendo un’opportunità unica per la terapia cellulare. Tuttavia, attualmente non esistono approcci per la sostituzione specifica delle microglia. Finanziato dal Consiglio europeo della ricerca, il progetto ReplaceMi si propone di sviluppare una strategia innovativa per sostituire le microglia embrionali utilizzando progenitori specifici. Avvalendosi di cellule staminali pluripotenti indotte, i ricercatori identificheranno i progenitori che possono incidere efficacemente nel cervello come le microglia. ReplaceMi studierà anche come trasformare le microglia in fabbriche di produzione di proteine per trattare i disturbi neurodegenerativi e identificherà le reti geniche per migliorare le risposte delle microglia alle malattie.
Obiettivo
Microglia are highly versatile brain resident cells that offer tremendous therapeutic opportunities. They are instrumental for maintaining healthy brain physiology and act as the primary modulators of neuroinflammation and disease. Microglial dysfunction has been convincingly linked to a myriad of neurological disorders, making these cells a prime target for therapeutic intervention. Remarkably, microglia are embryo-derived cells that self-maintain for life, with negligible replacement by the bone marrow. This astonishing self-renewal capacity offers a unique opportunity for cell therapy. The ability to replace dysfunctional microglia with healthy or genetically enhanced counterparts may transform the way we treat brain disease. But how can we replace a cell that is so adept at self-renewal in a tissue that is shielded from the periphery? Currently there are no translatable approaches for the specific replacement of microglia. Furthermore, bone marrow progenitors are unable to adopt the embryonic microglial phenotype. By building on our unpublished observations and developing innovative technologies, I aim to lay the foundation for microglial replacement therapy. We intend to develop an original and translatable strategy for the specific and near-complete replacement of embryonic microglia with adoptively transferred progenitors. Next, by combining iPSC differentiation with genetic barcoding, single-cell analysis and in vivo screening, we aim to identify progenitors that efficiently traffic to the brain and engraft as bona fide microglia. Moreover, we will investigate how we can transform microglia into local protein production factories, as a potential basis to treat neurodegenerative diseases. Finally, we will set up in vivo pooled CRISPR screens to identify the gene networks that can modulate and positively enhance microglial disease responses. ReplaceMi has the potential to result in a new and eagerly awaited breakthrough in treating brain disease.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
1050 Bruxelles / Brussel
Belgio