MND Accelerator Awards for Arpan Mehta and Raja Nirujogi

Published on 5 July 2024

Arpan Mehta and Raja Nirujogi, within months of being appointed as Independent Investigators at the MRC Protein Phosphorylation and Ubiquitylation Unit in the School, have each secured MND Accelerator (MNDAcc) Awards.

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From left: Dr Arpan Mehta and Dr Raja Nirujogi

MNDAcc, managed by Dementias Platform UK, is a £6 million investment by the Medical Research Council and National Institute for Health and Care Research to make the translation of discoveries into therapeutics easier for motor neuron disease (MND) and frontotemporal dementia (FTD).

Arpan, together with Dr Wenting Guo from ITI NeuroStra, University of Strasbourg, will perform an innovative kinome-wide CRISPR screen to aid in their search for druggable targets. They will do this by using patient-derived induced pluripotent stem cell lines from people with the C9ORF72 repeat expansion mutation, which is the commonest known genetic mutation underlying both MND and FTD. This process aims to identify proteins called ‘kinases’ that may act as pivotal cellular switches in the ALS/MND disease process. Arpan says, “We would like to determine which kinases prevent death of motor nerves. Kinases are excellent potential druggable targets, with >100 kinase-targeting drugs already approved. Thus, we may be able to find drugs that are already approved to use or be able to exploit the expertise already available at MRC PPU to develop new potential treatments for people with these diseases that could be tested definitively in clinical trials."

Raja, in collaboration with Dr. Selvaraj and Prof. Pal at The Anne Rowling Regenerative Neurology Clinic at the University of Edinburgh, will develop a highly sought blood-based biomarker assay for TDP-43 mediated motor neuron disease. They will employ transcriptomics, quantitative proteomics and proteogenomic analysis in identifying TDP-43 mediated aberrantly spliced transcripts and peptides termed “cryptic exons/peptides” in human peripheral macrophages. They aim to establish a compendium of TDP-43 mediated cryptic peptides in human blood cells in developing multiplexed high-resolution PRM-MS assay using the state-of-the-art mass spectrometry facility within MRC PPU. The developed assay will then be exploited to detect and quantify specific levels of cryptic peptides in peripheral macrophages and serum/plasma of deeply phenotyped and genotyped pwMND samples obtained through MND-SMART and CARE-MND. Raja says, “This project is the first step in establishing a multiplexed blood-based biomarker assay for MND disease pathology. The developed assay can be implemented as diagnostic and prognostic assay for MND.”

Dario Alessi, Director of the MRC PPU said, “Congratulations to Arpan and Raja for securing these important awards that will enable them to undertake exciting research relevant to better understanding, diagnosing and treating ALS. Going forward, it is a high priority for us to put our Unit’s expertise to use in deciphering ALS mechanistic biology, which complements well our other interests in neurodegeneration.”

Story category Awards and accolades