MA Cells Get Boost From Hydroxyurea

MDA grantee Ching Wang, a pediatric neurologist at Stanford (Calif.) University, was the senior investigator on a research team that recently demonstrated that adding the drug hydroxyurea to white blood cells taken from people with spinal muscular atrophy (SMA) increased the ability of these cells to produce SMN1, a protein needed but deficient in SMA.

Wang’s team added the drug to blood cells from five people with type 1 SMA (the most severe), five with type 2 (medium severity), five with type 3 (least severe) and five without SMA. It was effective at increasing SMN1 in all groups, although the increase was most significant in the SMA-affected cells.

The investigators, who published their results in the August issue of Annals of Neurology, say they believe the increase in SMN1 protein resulted from a change in the output from SMN2 genes, which carry almost identical instructions for making the SMN protein but can only produce a small amount of it. SMN2 genes mostly produce a closely related, but shorter, SMN protein.

The hydroxyurea apparently caused the SMN2 genes, which people with SMA have, to produce more of the longer, SMN1 protein.

“We are very encouraged by our findings that hydroxyurea is able to increase SMN protein production in white blood cells isolated from SMA patients,” Wang said. “We hope that we can see the same effects when we use hydroxyurea to treat SMA patients.

Wang and colleagues are testing hydroxyurea in people younger than 10 years with all types of SMA. For more information, contact Tony Trela at (650) 498-7658, or sma@stanfordmed.org; or visit http://sma.stanford.edu.