Towards the clinical implementation of TREM2 Microglia Engineering for treating DementiaSbroad
TREM2MEDS · Horizon Europe grant · 2024-04-01–2027-03-31
EC contribution
Total cost
Beneficiaries
About the data
Source: CORDIS (official EU open data), Horizon Europe. Framework HORIZON · call HORIZON-EIC-2023-TRANSITION-01 · scheme HORIZON-EIC · topic HORIZON-EIC-2023-TRANSITIONOPEN-01. CORDIS record →
Objective
TREM2MEDS emerges from the ERC PoC 2022 project TREM2μENGINES (Grant agreement ID: 101069395), which validated the efficacy of a novel treatment for Alzheimer’s Disease (AD) and Nasu-Hakola Disease (NHD) in murine models. A relevant proportion of AD cases and all forms of NHD are caused by pathogenic mutations in the TREM2 gene, which lead to microglia dysfunction contributing to and/or causing the onset and manifestations of AD and NHD. TREM2MEDS approach involves the transplantation of hematopoietic stem/progenitor cells (HSPCs) engineered by lentiviral vectors (LVs) to express robust levels of the Triggering receptor expressed on myeloid cells 2 (TREM2) in their central nervous system (CNS) myeloid/microglial progeny. The engineered cells have shown the ability to reduce and prevent Aβ accumulation, mitigate neuroinflammation and restore physiological scavenging functions in the diseased CNS, benefiting AD and NHD in robust animal models. In TREM2MEDS, we will exploit these findings for transition of the approach from TRL 4 to TRL 5/6 by generating IMPD-enabling data and packages that will allow launching, at project completion, a first-in-human Phase I clinical trial of TREM2-HSPC gene therapy in AD & NHD patients carrying TREM2 hypofunctional variants. The restoration of TREM2 function in microglia, by intervening on key mechanisms contributing to neurodegeneration, has the potential to overcome the limited efficacy of current treatments for AD, which only exert symptomatic but not curative effects. Through this work we will thus bring to clinical testing an approach intended to become the benchmark in the treatment of AD and NHD, and possibly other dementias.
Beneficiaries (4)
| Organisation | Country | Role | EC contribution | SME |
|---|---|---|---|---|
| UNIVERSITA DEGLI STUDI DI PADOVA | IT | coordinator | €1,732,131 | |
| USTAV MOLEKULARNI GENETIKY AV CR V.V.I. | CZ | participant | €499,415 | |
| INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE | FR | participant | €268,175 | |
| UNISMART - FONDAZIONE UNIVERSITA DEGLI STUDI DI PADOVA | IT | thirdParty | €0 |
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