Gamma-secretase allosteric modulation as preventive therapy in Alzheimer’s Disease
This project aims to validate gamma-secretase allosteric modulators as safe, effective, and affordable preventative treatments for Alzheimer's Disease using an innovative xenotransplantation model.
Projectdetails
Introduction
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.
Need for New Treatments
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.
Project Overview
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:
- Induction of neuro-inflammation
- Real Tau-pathology
- Granulovacuolar neurodegeneration
- Secretion of Tau biomarkers in the blood
All of these are characteristic of AD (PMID37708272).
Collaboration and Treatment
We will treat this model in collaboration with a contractor with a newly developed compound to demonstrate that this GAM can prevent AD pathology in a safe and effective way.
Experimental Evidence
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 signaling and does not show mechanistic-driven side effects.
Goals of the Experiments
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.
Financiële details & Tijdlijn
Financiële details
Subsidiebedrag | € 150.000 |
Totale projectbegroting | € 150.000 |
Tijdlijn
Startdatum | 1-9-2024 |
Einddatum | 28-2-2026 |
Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- VIB VZWpenvoerder
Land(en)
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