Identifying novel neuroprotective mechanisms in motor neuron disease

About the project

Our research focuses on understanding the degeneration and regeneration of peripheral axons and synapses, and identifying strategies to protect motor neurons and encourage regeneration.

Our primary focus is on the childhood motor neuron disease Spinal Muscular Atrophy, but we are also interested in drawing parallels between adult and childhood forms of motor neuron disease, and identifying neuroprotective and neuroregenerative strategies which are effective in multiple types of motor neuron disease.

Current projects include:

Investigating motor unit recovery following Smn restoration and determining how delayed Smn restoration affects the recovery of the motor unit
Understanding pressures put upon enlarged motor units and developing ways to support them
Investigating novel approaches to encourage regeneration following administration of approved drugs in SMA
Identifying novel mechanisms involved in neuromuscular junction regeneration.

Funder(s)

Anatomical Society, Muscular Dystrophy Association, Cure SMA, SMA Foundation, Muscular Dystrophy UK

Publication(s)

Comley, L.H., Kline, R.A., Thomson, A.K., Woschitz, V., Landeros, E.V., Osman, E.Y., Lorson, C.L. and Murray, L.M.

Motor Unit Recovery Following Smn Restoration in Mouse Models of Spinal Muscular Atrophy.

Hum Mol Genet, 31:3107 (2022)

DOI: 10.1093/hmg/ddac097

Woschitz V, Mei I, Hedlund E, Murray LM

Mouse models of SMA show divergent patterns of neuronal vulnerability and resilience.

Skelet Muscle. 12:22 (2022)

DOI: 10.1186/s13395-022-00305-9

Mole, A.J., Bell, S., Thomson, A.K., Dissanayake, K.N., Ribchester, R.R. and Murray, L.M.

Synaptic withdrawal following nerve injury is influenced by postnatal maturity, muscle-specific properties, and the presence of underlying pathology in mice.

J Anat, 237, 263-274 (2020)

DOI: 10.1111/joa.13187

Villalón E., Kline RA., Smith CE., Lorson ZC., Osman EY., O’Day S., Murray LM., Lorson CL.

AAV9-Stathmin1 gene delivery improves disease phenotype in an intermediate mouse model of Spinal Muscular Atrophy

Hum Mol Genet. Nov 15;28(22):3742-3754 (2019)

DOI: 10.1093/hmg/ddz188

Courtney NL, Mole A, Thomson A., Murray LM.

Reduced P53 levels ameliorate NMJ loss without affecting motor neuron pathology in a mouse model of SMA

Cell Death and Disease 10:515 (2019)

DOI: 10.1038/s41419-019-1727-6

Kline RA., Dissanayake KN., Hurtado ML., Ahl A., Lamont DJ., Ribchester RR., Court F., Wishart TM., Murray LM

Altered mitochondrial bioenergetics are responsible for the delay in Wallerian degeneration observed in neonatal mice.