Repurposing AMPAkines for enhancing myelin regeneration in multiple sclerosis (360G-Wellcome-204488_Z_16_Z)

Multiple sclerosis (MS) affects around 2.5 million worldwide, and there are no fully effective treatments currently available. Myelin regeneration can occur spontaneously in demyelinating diseases such as MS, and is essential for functional recovery. However, it often fails, leading to sustained clinical disability. Thus, promoting myelin regeneration is an important therapeutic aim. The recent research of Dr Káradóttir and colleagues has revealed an important regulatory mechanism of how the brain can repair itself. The team identified novel communication between stem cells, which are capable of repairing myelin damage, and nerve fibres that have lost myelin (as occurs in MS). When we deliver a drug that increases the ‘sensitivity’ of the stem cells to these signals from nerve fibres, we augment the capability of the stem cells to repair myelin damage. The aim of this pathfinder award is to further validate this as a therapeutic strategy and provide clear proof of concept evidence for the use of drugs that augment the stem cells sensitivity to electrical signals from nerve fibres, to promote myelin regeneration in MS. The future impact of identifying a pharmacological agent that is effective in augmenting myelin regeneration is immense; potentially revolutionising treatments for a number of white matter diseases in addition to MS.