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.

Subsidie
€ 150.000
2024

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

Startdatum1-9-2024
Einddatum28-2-2026
Subsidiejaar2024

Partners & Locaties

Projectpartners

  • VIB VZWpenvoerder

Land(en)

Belgium

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