Summaries of MND/amyotrophic lateral sclerosis (ALS) funded grants
Brain commands and beyond: decoding inner speech for neural prosthetics
Dr Oiwi Parker Jones, University of Oxford, £1,351,705
This career development award aims to create a neural speech prosthetic to restore communication to patients who are unable to control their vocal articulators due to brain stem stroke or MND.
Interrogation of links between risks and early pathogenesis at single cell resolution in a novel human ALS organoid neuraxis model
Dr Andras Lakatos, University of Cambridge, £2,045,118
This senior clinical fellowship award will use a newly developed model system, created from patient cells, to study the molecular changes in individual cells and understand the initiation and progression of ALS. This may help to identify early markers of ALS which can help to guide treatment.
Small molecule modulators of lncRNA NEAT1_2: a novel approach to enhancing the endogenous neuroprotective response in ALS
Professor John Atack, Cardiff University, £153,440
Funded through the MRC/AstraZeneca Centre for Lead Discovery, this project aims to identify small molecules that bind to the long non-coding RNA NEAT1_2 to stabilise it and increase expression.
NEAT1_2 is essential to paraspeckle formation (protein complexes that perform a neuroprotective function in ALS) therefore these small molecules could increase paraspeckle formation and reduce degeneration of motor neurons in ALS.
Mechanistic studies of ALS-causative mutations and RNP-focused drug discovery using in vitro reconstitution of RNP complexes
Dr Tatyana Shelkovnikova, The University of Sheffield, £374,676
This research grant investigates the link between protein complexes called paraspeckles and ALS.
The RNA that induces formation of these paraspeckles becomes accumulated in ALS motor neurons, therefore the investigators aim to find small molecules that can modulate the complexes, with the potential for such molecules to be used in research and drug discovery.
Structural and functional studies of the VAPB-PTPIP51 ER-mitochondria tethering proteins in neurodegenerative diseases
Professor Christopher Miller, King’s College London, £1,083,310
This research grant investigates the role of GSK3beta and AMP Kinase in regulating binding of VAPB-PTPIP51 to ER-mitochondria and whether disruption of this induces neurodegenerative disease.
Damage to functions regulated by ER-mitochondria signalling, mediated by VAPB-PTPIP51, is a feature of ALS therefore this work could facilitate the design of potential therapeutics.
Synaptic pathology in ALS-FTD
Professor Seth Grant, The University of Edinburgh, £609,489
Funded through the MRC-AMED neurosciences funding opportunity, this collaborative project studies the pathology of synapses in ALS and FTD and aims to correlate this with behavioural phenotypes.
This could aid understanding of the nature of vulnerable and resilient synapses and how molecular perturbations can impact specific synapses, circuits and brain regions.
Energy metabolism in motor neuron diseases
Dr Kiterie Faller, The University of Edinburgh, £1,362,657
This clinician scientist fellowship investigates changes in metabolism in two mouse models of MND in order to identify common changes that could be used as therapeutic targets.
Targets found will be validated in patient samples before selected metabolic pathways are modulated to test whether this can reverse pathological changes.