Valproic Acid Improves Strength, SMN Levels In SMA

The drug valproate (valproic acid), currently used for seizures, bipolar disorder and migraine headaches, increased objective and subjective strength assessments in six adults with type 3 or 4 (defined as “able to walk at some point”) spinal muscular atrophy (SMA).

Laboratory experiments have suggested that valproate can increase the level of full-length SMN protein molecules, needed but deficient in SMA, in cells from people with the disease.

Conrad Weihl and colleagues, who published their findings Aug. 8 in Neurology, gave valproate to seven people, ages 17 to 45, with SMA, for an average of eight months. Alan Pestronk, MDA clinic director at Washington University in St. Louis, was on the study team.

The average strength gain from right before starting valproate to the last clinic visit was 48 percent. One person, a wine maker, was able to return to picking grapes; and another, a high school student, was able to return to marching in the band. Others noted improvements in their ability to rise from a chair, dress themselves or breathe deeply. One participant withdrew from the study after one month because of concerns about weight gain.

In another study, published in the June issue of Annals of Neurology, researchers in Germany say they’ve found evidence that valproic acid can increase full-length SMN levels in SMA carriers and patients.

Lars Brichta at the University of Cologne (Germany) and colleagues, who studied 20 people with SMA and 10 SMA carriers taking valproic acid, caution that they measured blood cell SMN levels, which may not correlate with SMN levels in nerve cells or with muscle strength. However, they call the finding “a major step toward the development of a treatment for SMA.”