CoEN Developing preclinical and clinical biomarkers of NRF2 pathway activation for therapeutic application in neurodegenerative diseases.

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Neurodegenerative diseases such as Alzheimer's (AD) and motor neuron disease (ALS/MND) cause cell death of different populations of nerve cells. These conditions are very distressing for sufferers and their families. There is a severe lack of treatments available to slow disease progression and clinical trials have had high failure rates partly because there is no way to demonstrate that a drug is reaching the nervous system in the right amounts to protect the nerve cells from injury. Although the underlying causes that trigger these diseases are complex (multiple genes and environmental factors), there is substantial overlap in the cell pathways that lead to neurodegeneration.This project is focused on a master cellular pathway (sometimes called the programmed cell-life pathway) controlled by a molecule NRF2 that promotes cell survival in the face of stresses such as oxidative stress, inflammation, and failure of the energy-generating and protein quality-control pathways within neurons which are known to contribute to neurodegeneration. Our aim is to develop MRI imaging and body fluid markers to show NRF2-activating drugs working in the body. These results will be applied later in clinical trials to test the effectiveness of NRF2 activators for patients with MND and AD.