Funder: Wellcome Trust Project Code: 204571
Funder Contribution: 98,887 GBP
Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder primarily affecting children, which is caused by depletion of the ubiquitously expressed survival motor neuron (SMN) protein. Studies in SMA patients and murine SMA models have shown that increased SMN protein levels are associated with milder forms of the disease. In this scenario, identifying the pathways and drug compounds that increase SMN levels would suggest a direct therapeutic strategy for treating SMA patients. However, another complementary approach could be considered: the identification of pathways that act independently of SMN function and can be corrective to SMN reduced levels. Manipulation of these pathways can increase the effective activity of the SMN protein already present in SMA patients. I have recently identified conserved genetic pathways that impact SMN neuromuscular function on a previously defined invertebrate Caenorhabditis elegans (C. elegans) model of SMA. The proposed project focus will be to use the powerful genetic tools of C. elegans to dissect the mechanism(s) by which the aforementioned cross-species pathways control SMN synaptic function. The ultimate goal is to identify novel therapeutic avenues that will attenuate SMA in mammalian models and human patients.
