Kentaro Sahashi, a postdoctoral research scientist at the Cold Spring Harbor Laboratory in Cold Spring Harbor, N.Y., was awarded an MDA development grant (DG) totaling $180,000 over a period of three years to study the roles of the SMN protein in spinal muscular atrophy (SMA). (MDA development grants are awarded to exceptional postdoctoral candidates who have the best chance of becoming independent researchers and future leaders of neuromuscular disease research.)

SMA is caused by mutations in the SMN1 gene, resulting in a deficiency of SMN protein. Humans have a closely-related SMN2 gene that also expresses functional SMN protein, but only in minute amounts due to differences in splicing, a cellular editing process that occurs during protein production.

In mice with an SMA-like disease, Sahashi and colleagues plan to use synthetic molecules called antisense oligonucleotides (ASOs) to influence and evaluate different SMN2 splicing patterns and determine whether they have potential therapeutic value.

The investigators plan to study the effects of ASOs in different tissues, administered via different delivery methods, and at different developmental stages. They expect to gain insight into the roles of the SMN protein in the SMA disease process, as well as an understanding of its normal functions in both the central nervous system and peripheral tissues.

"This in turn," Sahashi said, "will contribute to the ongoing development of targeted therapeutics and the establishment of a useful therapeutic time window."

Funding for this MDA grant began February 1, 2012.