Systematic assessment of microRNA-132 supplementation to treat Alzheimer’s disease

ADMIR: Systematic assessment of microRNA-132 supplementation to treat Alzheimer’s disease

This project is a strategic partnership between academia and pharmaceutical industry, i.e. the Netherlands Institute for Neuroscience and Janssen Pharmaceutica, focused on generating innovative therapeutics for the treatment of Alzheimer’s disease (AD). The aim is to systematically test the suitability of microRNA-132 as a therapeutic target for AD.

By 2040, dementia patients in the Netherlands will double, reaching approximately 500.000, while there will be an estimated 130.000.000 dementia patients worldwide by 2050. AD comprises 50-75% of all dementia cases. AD cannot be currently prevented, slowed down or cured, being one of the main causes of disability later in life, ahead of cancer, cardiovascular disease and stroke. Ameliorating pathology can substantially improve life quality of patients, their families and care givers, while it will also reduce the cost of social care expected to triple by 2040. AD is a complex, multifactorial disorder: all clinical trials have failed this far, mainly because of targeting only one single molecule or pathway along with inadequate preclinical validation.

In this project, the therapeutic potential and safety of a microRNA-based strategy for AD treatment will be systematically assessed. Using novel animal and cell models and developing innovative tools for non-invasive brain delivery, this project will validate microRNA supplementation as a novel therapeutic approach to tackle AD complexity. More specifically, they propose that increasing the levels of microRNA-132 (a microRNA regulating several physiological brain functions and decreasing in human AD brain) in AD brain, can restore multiple aberrant cellular and molecular processes, and thereby improve memory deficits.

This project will help:
A. identifying the complex mechanisms of microRNA-132 function in healthy and AD brain,
B. develop novel tools for non-invasive delivery of RNA-based therapeutics into the brain, and,
C. systematically address the functional effects, safety and thereby suitability of microRNA-132 as a target for further drug development in AD.

Summary

MicroRNAs, small RNA molecules present in all our cells, play essential roles in healthy brain and are deregulated in Alzheimer’s disease. This project proposes that supplementing the levels of microRNA-132 that decreases in the brain of Alzheimer’s disease patients, can improve pathology and memory loss, by restoring neuronal function and inflammation.

Technology Readiness Level (TRL)

1 - 4

Time period

48 months

Partners