MND Mechanisms In Vivo
Research type
Research Study
Full title
Deciphering pathophysiological mechanisms underpinning riluzole efficacy to inform development of new treatments in motor neuron disease
IRAS ID
293206
Contact name
Nigel Hoggard
Contact email
Sponsor organisation
Sheffield Teaching Hospitals NHS FT
Duration of Study in the UK
3 years, 9 months, 31 days
Research summary
The idea behind this study is to harness recent advances in scanning technology to assess a number of different disease mechanisms all at the same time, each thought to be potentially important in motor neuron disease (MND), in people living with the condition. The aim is to determine which disease mechanism is the key biological pathway influenced by riluzole, as this is still the only medication shown to have any effect on survival in MND, and the mechanism of benefit remains uncertain. This is an important question to answer because if the key disease mechanism can be identified, it can be targeted in preference to other potential candidates, which may just be bystanders, to develop more effective drugs, and ensure they are affecting their target in people living with MND. This step- showing benefit in people living with MND, rather than laboratory or animal models- is the stage at which many potential treatments in the past have failed. The advantage of using riluzole in this context is that it is the only medication to have any influence on survival, so pathways that it affects must be important and relevant to a person’s outcome, rather than irrelevant secondary changes. This is a very important distinction when deciding on which of a variety of promising new drugs emerging from laboratory research to focus upon, in order to maximise the chances of success in trials.
In addition to scans, fluids including blood and spinal fluid will be analysed to help understand how riluzole enters the brain and to measure its effect on inflammation. A neurophysiology technique known as transcranial magnetic stimulation will also be applied (which involves painless and harmless application of magnetic pulses to the brain, and measurement of electrical responses). This will enable a detailed picture of the impact of a number of different disease mechanisms to be built up and compared before and after starting treatment with riluzole. This is the unique aspect of this study; never before have these multiple disease mechanisms been measured concurrently in MND.REC name
South West - Frenchay Research Ethics Committee
REC reference
21/SW/0024
Date of REC Opinion
7 May 2021
REC opinion
Further Information Favourable Opinion