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Gamma-secretase allosteric modulation as preventive therapy in Alzheimer’s Disea...

Gamma-secretase allosteric modulation as preventive therapy in Alzheimer’s Disease The recent advent of therapeutic Aβ-antibodies has validated amyloid plaques as drug targets in Alzheimer’s Disease (AD). They remain expensive, prone to side effects, and clinical benefit is limited. The field needs a safe and ch... ver más

28/02/2026

VLAAMS INSTITUUT...

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VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-09-01

ERC-2023-POC: ERC PROOF OF CONCEPT GRANTS Objective:Objectives:The ERC Proof of Concept Grants aim at facilitating exploration of the commerci...

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VLAAMS INSTITUUT BIOTECHNOL...

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Duración del proyecto: 17 meses Fecha Inicio: 2024-09-01
Fecha Fin: 2026-02-28

Líder del proyecto

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The recent advent of therapeutic Aβ-antibodies has validated amyloid plaques as drug targets in Alzheimer’s Disease (AD). They remain expensive, prone to side effects, and clinical benefit is limited. The field needs a safe and cheap drug, preferably a small compound that can be taken orally, and in a preventative way before brain damage has occurred. Despite strong theoretical potential, further clinical development of gamma-secretase allosteric modulators (GAM), is currently hampered by the lack of strong experimental evidence that they are safe and can effectively prevent AD. In this POC we will exploit findings of our ERC grant Cellphase-AD to generate such evidence. We developed an innovative xenotransplantation model beyond the classical mouse models, as it shows not only amyloid plaques, but also the induction of neuro-inflammation, real Tau-pathology, granulovacuolar neurodegeneration, and secretion of Tau biomarkers in the blood, all characteristic of AD (PMID37708272). We will treat this model in collaboration with a contractor with a newly developed compound to demonstrate that this GAM can prevent in a safe and effective way this AD pathology. Using an innovative unbiased ʏ-secretase assay we will provide direct evidence that this GAM, in contrast to the previously failed gamma-secretase inhibitor Semagacestat, maintains normal processing and signalling and does not show mechanistic driven side effects. The experiments aim to support the concept that GAM can be developed as preventative medication in both sporadic and familial AD and to bring the compound forward to clinical trialing.

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