Project to test combinations of drugs aims to speed up delivery of urgently needed treatments for motor neuron disease

A new project by UK DRI researchers aims to identify combinations of existing drugs that could be used together to treat motor neuron disease (MND).

Led by Prof Siddharthan Chandran, Group Leader at the UK DRI at Edinburgh and Director of the Euan MacDonald Centre for MND Research and recently appointed as the new UK DRI Director, the £3.3 million project is funded by the medical research charity LifeArc, as part of an ongoing partnership between the charity and the UK DRI.

The partnership brings together the strengths of UK DRI’s research into discovery science with LifeArc’s translational expertise to take exciting lab discoveries forward and translate them into tangible benefits for patients.

MND is a life-limiting condition that causes progressive weakness of the muscles due to the degeneration of motor neurons in the brain and spinal cord. There is currently only one drug approved to treat the disease in the UK, riluzole, which has only a modest effect.

There is an urgent unmet need for effective therapies to treat MND. But the brain is complex, and targeting one biological pathway with a single drug might not be enough to slow down or stop the degeneration of motor neurons. The new project seeks to drastically accelerate the development of new treatments by identifying existing drugs which target multiple disease mechanisms implicated in MND. Typically, new drugs can take up to 15 years to progress through development and clinical trial stages, but with this approach, treatments could be tested in the clinic within four years.

In the first stage of the study, the researchers will prioritise the top drug candidates, using both laboratory-based tests on motor neurons grown in the lab from patient donated stem cells, and a machine-learning, artificial intelligence approach to review published scientific studies of MND.

Next, the top candidate drugs will be tested in pairs in combination in the stem cell models of MND, against different biological pathways known to be implicated in MND.

The ultimate goal is to seek regulatory approval to test the most promising and effective combinations of drugs in the Euan MacDonald Centre’s MND-SMART (Motor Neuron Disease – Systematic Multi-arm Adaptive Randomised Trial) trial. Earlier this month, MND-SMART received £2.5 million in funding from MND Scotland and the MND Association. This pioneering trial across 20 sites in the UK is designed to shorten the time it takes to find medicines that can slow or stop MND. Unlike typical clinical trials which test a single treatment, MND-SMART is testing several treatments at the same time. It is also an adaptive trial which means that new drugs can be added, and those proven ineffective can be dropped.

This new project complements another recently announced MND initiative, EXPERT-ALS, which aims to rapidly identify promising drug candidates in small scale trials, before definitive evaluation in Phase 3 platform trials such as MND-SMART.

Dr Paul Wright, MND Translational Challenge Lead at LifeArc said:

“Our involvement in this research is part of an ambitious long-term £100m funding programme we have launched to help tackle neurodegenerative conditions and find treatments where none currently exist. By working with UK DRI we are uncovering promising life science research, like Prof Chandran's, that we can support with funding or by offering our scientific resources and expertise in translational research. Ultimately, our aim is to accelerate the process of finding medical breakthroughs that can prevent and stop these life-threatening diseases progressing.”

To find out more about Prof Siddharthan Chandran's research, visit his UK DRI profile. To stay up to date on the latest research news and institute updates, sign up to receive our monthly newsletter, ‘Inside Eye on UK DRI’.

Article published: 29 June 2023
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