Target induction of the cold-shock protein RBM3 to prevent synapse loss and neurodegeneration in ALS/FTD

PI Dr Marc-David Ruepp
Co-investigators Dr Andrea Serio
Collaborators Prof. Pietro Fratta and Prof. Rickie Patani
PI organisation King’s College London & UK DRI
Funding awarded £428,829
Completion date 31st December 2025 (19 months)

In MND the connection between different nerve cells, synapses, are lost very early on, even before any clearly visible disease symptoms. The aim of this project is to establish whether RBM3, a cold-shock protein that was shown to be neuroprotective in Alzheimer’s and prion disease by preserving synapses could be harnessed also as therapeutic approach for ALS/FTD. For this, we plan to exploit a novel system we developed that allows recreating complex but controlled networks of neurons in a dish to assess whether synapse health in diseased neurons improves upon delivery of therapeutic antisense RNAs that increase RBM3 levels. We will establish here whether increasing RBM3 levels can preserve synapses in MND and therefore whether it can be harnessed as a therapeutic approach.