NRF2 Biomarkers study

  • Research type

    Research Study

  • Full title

    Developing Clinical Biomarkers Of NRF2 Activation For Therapeutic Application In Neurodegenerative Disease

  • IRAS ID

    248860

  • Contact name

    Pamela J Shaw

  • Contact email

    pamela.shaw@shef.ac.uk

  • Sponsor organisation

    Sheffield Teaching Hospitals NHS Foundation Trust

  • Clinicaltrials.gov Identifier

    STH19982, STH number

  • Duration of Study in the UK

    2 years, 0 months, 1 days

  • Research summary

    Neurodegenerative diseases such as Alzheimer's disease (AD) and motor neurone 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 nerve cells, 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.

    The study will recruit 30 patients with MND and 30 controls (healthy people or people with non-neurodegenerative diseases); and each participant will be asked to attend two study visits – Baseline and approximately 4 months later.

    Study procedures at each visit will be the same (to assess how things have changed over time), and include:
    • MRI scan of the brain
    • Lumbar puncture (LP) to collect cerebrospinal fluid (CSF)
    • Blood samples
    • Skin sample (only required at one study visit).

  • REC name

    Yorkshire & The Humber - Sheffield Research Ethics Committee

  • REC reference

    18/YH/0253

  • Date of REC Opinion

    12 Jul 2018

  • REC opinion

    Favourable Opinion