by Brunhilde Wirth
Institute of Human Genetics of the University of Cologne, Germany

Here we report on our paper entitled “In vivo activation of SMN in SMA carriers and patients treated with valproate” by Brichta L, Holker I, Haug K, Klockgether T & Wirth B. Annals of Neurology, 2006, April 10, advanced online publication.

In July 2003, we reported that valproic acid (VPA) was able to increase full-length SMN2 transcript and protein levels by 2fold to 4fold in fibroblasts derived from SMA patients (Brichta et al. Hum Mol Genet, 2003). Similar results were shown by the group of K. Fischbeck and published in November 2003 (Sumner et al., Ann Neurol 2003). Furthermore, we have been able to demonstrate that VPA significantly increases SMN RNA/protein levels in cultured brain slices from rat and humans (obtained after surgery of epilepsy patients) as well as in cultured rat embryonic motor neurons (Hahnen et al., J Neurochemistry, 2006, in press).

VPA is a well-explored FDA-approved drug that rarely shows any severe side effects in long-term therapy of epilepsy patients. This makes it available for a straightforward application in humans.

Meanwhile, we studied the effect of VPA in blood from SMA carriers and patients to address the following questions: (1) Is VPA capable of acting on the in vivo FL-SMN transcript/protein level, and (2) how suitable is the use of blood for the development of a biomarker that would allow monitoring of the drug response in VPA-treated SMA patients?
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