Investigation of pharmacodynamic markers of NRF2 activity
Research type
Research Study
Full title
Investigation of pharmacodynamic markers of NRF2 activity in peripheral blood of multiple sclerosis patients receiving dimethyl fumarate.
IRAS ID
266236
Contact name
Adeeb Rehman
Contact email
Sponsor organisation
University of Liverpool
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Dimethyl fumarate (DMF; Tecfidera) is relatively new first line therapy in patients with multiple sclerosis (MS). DMF is a known activator of NRF2, which regulates the expression of several hundred cell defence genes. We aim to collect and analyse peripheral blood from MS patients before and after initiating DMF therapy, to characterise changes in the expression of NRF2-regulated genes and proteins which could represent blood-based markers of its activity. The measurement of such markers will enable pharmacodynamic changes in NRF2 activity to be linked to therapeutic outcomes, both in DMF-treated MS patients and, ultimately, other patient cohorts receiving NRF2 activators as novel therapeutic interventions.
Our study will be conducted primarily at The Walton Centre in Liverpool, where around 50 MS patients are commenced on DMF therapy every year. We will collect blood from patients prior to initiation of DMF therapy, 2 weeks after the patient has been moved to the full therapeutic dose of DMF, and at their routine 3 month check up. We will isolate serum and whole blood RNA from each of the samples, to facilitate analysis of candidate protein and gene markers, respectively. Samples will be stored for up to 5 years, after which they will be destroyed.
REC name
East of England - Cambridge South Research Ethics Committee
REC reference
19/EE/0319
Date of REC Opinion
15 Nov 2019
REC opinion
Further Information Favourable Opinion