Tomoyuki Awano, a postdoctoral research scientist in the department of pathology and cell biology at Columbia University Medical Center in New York, was awarded an MDA development grant (DG) totaling $180,000 over a period of three years to search for genes that modify the onset and disease course of 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 the deletion of the SMN1 gene and a resulting deficiency of functional SMN protein. In humans, a nearly identical gene called SMN2 produces some partially functional SMN protein. Typically, the greater the number of copies a person with SMA has of the SMN2 gene, the less severe the disease.

But sometimes the SMN2 copy number doesn’t predict a person’s disease course.

This has been demonstrated in families, where multiple members are missing the SMN1 gene and have the same number of copies of SMN2, but whose SMA turns out drastically different. In previous work, Awano and colleagues have confirmed that this inconsistency is observed also in mouse models of SMA. A possible explanation is "modifier genes" that influence the disease course via the modulation of different biological pathways.

"Identifying modifier genes will not only reveal a potential target for cures, but will also shed light on the unknown disease mechanisms of SMA," Awano said.

Funding for this MDA grant began February 1, 2012.