Valproic Acid May Treat Spinal Muscular Atrophy

The results, suggesting that valprioc acid may treat SMA, were published in the November 2003 issue of the Annals of Neurology.

The cells were taken from patients with SMA type 1, the most devastating form of the disorder. There are a number of variations of the disease, with different life expectancies. All three forms of childhood-onset SMA are linked to mutations in the same gene, called SMN1, which produces a protein by that name. Patients with a relatively large amount of SMN1 protein tend to have milder symptoms.

Another gene, called SMS2, is almost identical to SMN1 and on the same chromosome. Although the normal form of SMN1 produces a full-length functional protein, most of that produced by SMN2 is truncated and not able to function. The SMN2 gene, however, produces a small amount of normal SMN protein, which can reduce the disease's severity. Because of this, researchers are looking for drugs that could increase the amount of protein it produces. In the study, they tested valproic acid, commonly used to treat epilepsy, to see if it could increase the amount of protein. They discovered that the more they gave, the greater the amount of gene activity. The drug also increased production of functional SMN protein by 30-50%.

The researchers are also looking at other solutions, because treatment with valproic acid could lead to liver toxicity, especially in young children. Valproic acid belongs to a class of drugs called histone deacetylase (HDAC) inhibitors, which increase the activity of certain genes. Other HDAC inhibitors might also be useful for treating SMA. The researchers have developed a blood test to help them track the level of SMN protein in patients, which will tell them how a particular drug is working.

"Even if this isn't the best drug for SMA, there is still promise for this class of drugs,” said Charlotte J. Sumner, M.D., of the National Institute of Neurological Disorders and Stroke (NINDS, Bethesda, MD, USA).





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