King's Researchers Receive £1.4M to Hasten MND Treatment Development

The projects are part of a £5.8 million investment by the Medical Research Council and the National Institute for Health and Care Research (NIHR) to speed up the development of treatments for MND, and the related condition of Frontotemporal dementia (FTD).

Improving clinical trial designs to address the urgent need for MND treatment

Professor Ammar Al-Chalabi was awarded £642,768 to develop a set of digital twins of people with MND to better clinical trial designs. He will be working with co-investigators Dr Alfredo Iacoangeli and Professor Ben Carter from the IoPPN.

There is currently only one drug licensed for the treatment of MND in the UK. The project, "Virtual clinical trial populations in motor neuron disease", addresses the urgency to develop better treatment by examining current clinical trial designs.

Researchers will use computer simulations to carry out clinical trial selection on the digital twins to replicate what would happen in a real-life trial. This will inform the researchers on aspects of the design that can be improved, making the clinical trial shorter and more efficient. Using a digital twin, the clinical trial can also address the issue of placebo use and allow more people to receive the real treatment, which is an important issue in a terminal condition such as MND.

Investigating RBM3 as a potential therapeutic target

Dr Marc-David Ruepp and co-investigator Dr Andrea Serio from the UK Dementia Research Institute at King's were awarded £428,829 to investigate the protein RBM3 as a potential therapy for MND/FTD. They will collaborate with Professor Pietro Fratta and Professor Rickie Patani from University College London.

The project, "Target induction of the cold-shock protein RBM3 to prevent synapse loss and neurodegeneration in ALS/FTD", combines the teams' expertise to better understand the complex biological mechanism underlying MND and to explore new therapeutic targets.

In MND the connection between synapses (the sites of connection and communication between nerve cells) are lost in early stages even before symptoms appear. In this project the researchers will look at RBM3, a protein that has been shown to be able to preserve synapses and prevent neuronal cell death in Alzheimer's and prion disease. Using a novel system, they will create the neuronal network in a dish to assess the effect of therapeutic antisense RNAs that increase RBM3 level.

Identifying personalised indicators of ALS onset and progression

Dr Alfredo Iacoangeli was awarded £399,265 to investigate if molecular subtypes of ALS can be used to accurately diagnose the disease and predict its progression. He will work with co-investigators Professor Ammar Al-Chalabi and Dr Ahmad Al-Khleifat (IoPPN), and collaborators Professor Gerome Breen (IoPPN), Dr Heather Marriott (IoPPN) and Professor Janine Kirby (University of Sheffield).

The project, "Validating ALS Molecular Subtypes for Diagnostics and Disease Stratification", builds on the team's previous work which demonstrated that we could group people with ALS into three molecular subtypes based on gene expression patterns in the brain, identified using machine learning. These subtypes can accurately differentiate patients from non-affected individuals and are consistent across ALS datasets from different populations. This suggests they could be used for diagnosing ALS and predicting its progression.

The researchers will investigate the accuracy of this method using a large dataset. They will analyse blood samples to group people with ALS by molecular subtype, and determine if this approach can be used to diagnose ALS, predict its progression, and ultimately guide treatment planning.

King's is one of eight institutions across the UK which received a 2024 MND Accelerator Award, and the only to receive funding for three projects. The awards were part of the £50 million government investment in the new MND Research Institute (co-led by King's and Sheffield, with Universities of Oxford, Edinburgh, Edinburgh, Liverpool and UCL).