Education & Training:
Hammersmith Hospital, University London, Ph.D.
Hospital for Sick Children, University of Toronto, Postdoctoral Fellow

Research Interest:
The laboratory focuses on the neuromuscular disorder Spinal Muscular Atrophy (SMA). We developed the Delta 7 SMA mouse model that has been used extensively to develop therapeutics. Using this mouse model and many others we showed that the SMN protein is reduced in SMA and that the severity of the phenotype is dependent amount of functional SMN. We have shown rescue of SMA mice and pigs with scAAV9-SMN (Zolgensma) and this has led to approval of Zolgensma for treatment of SMA. Recently we demonstrated that co administration of an antisense oligo morpholino with a SMN inducing drug (Risdiplam) increase full-length SMN production from SMN2 and improved symptomatic treatment. We are currently using missense mutations identified in patients, along with suppressors, in mice and cell culture to study the oligomeric SMN protein and determine the critical function of SMN that gives rise to SMA. Finally, using bioinformatics we are studying the DNA differences in SMA patients whose SMN2 copy number does not correlate with the phenotypic SMA severity. We can potentially identify genes that modify the SMA phenotype.

Selected Publications:

• • • Thomsen, G., A. H. M. Burghes, C. Hsieh, et al. (2021). “Biodistribution of onasemnogene abeparvovec DNA, mRNA and SMN protein in human tissue.” Nat Med 27(10): 1701-1711.

• • • Kray, K. M., V. L. McGovern, D. Chugh, et al. (2021). “Dual SMN inducing therapies can rescue survival and motor unit function in symptomatic 7SMA mice.” Neurobiol Dis 159: 105488.

• • • Blatnik, A. J., 3rd, V. L. McGovern and A. H. M. Burghes (2021). “What Genetics Has Told Us and How It Can Inform Future Experiments for Spinal Muscular Atrophy, a Perspective.” Int J Mol Sci 22(16).

• • • McGovern, V. L., K. M. Kray, W. D. Arnold, et al. (2020). “Intragenic complementation of amino and carboxy terminal SMN missense mutations can rescue Smn null mice.” Hum Mol Genet 29(21): 3493-3503.

• • • Blatnik, A. J., V. L. McGovern, T. T. Le, et al. (2020). “Conditional deletion of SMN in cell culture identifies functional SMN alleles.” Hum Mol Genet 29(21): 3477-3492.

• • • Mendell, J. R., S. Al-Zaidy, R. Shell, et al. (2017). “Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy.” N Engl J Med 377(18): 1713-1722.

• • • Duque, S. I., W. D. Arnold, P. Odermatt, et al. (2015). “A large animal model of spinal muscular atrophy and correction of phenotype.” Ann Neurol 77(3): 399-414.

• • • Porensky, P. N., C. Mitrpant, V. L. McGovern, et al. (2012). “A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse.” Hum Mol Genet 21(7): 1625-1638.

• • • Foust, K. D., X. Wang, V. L. McGovern, et al. (2010). “Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN.” Nat Biotechnol 28(3): 271-274.

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