( ctivity of certain genes in the body. ...)Treatment Extends Survival in Mouse Model of Spinal Muscular Atrophy,Health

ctivity of certain genes in the body.

Previous studies have shown that HDAC inhibitors can increase the amount of SMN2 expression in cultured cells and that treating pregnant mice with an HDAC inhibitor can increase the survival of their babies with SMA. Preliminary clinical trials are now underway to test several HDAC inhibitors in children who have SMA. However, the drugs in those clinical trials are weak HDAC inhibitors with other biological effects that may limit their usefulness for treating this disease. More importantly, none of the previous studies has demonstrated that HDAC inhibitors can extend survival when delivered after symptoms appeared.

In the new study, the investigators tested TSA, which is a potent HDAC inhibitor, in cells from SMA patients and in a mouse model of SMA. They found that the drug increased the amount of SMN2 gene activity in both the cultured cells and the mouse model.

Next, the researchers gave daily injections of TSA to the SMA mice, starting when the mice were 5 days old. By that time, the mice showed clear symptoms of disease: they were significantly underweight and they had a markedly impaired righting reflex, or ability to get on their feet after being placed on their backs. The treated mice lived 19 percent longer, on average, than mice that did not receive TSA. About three-fourths of the treated mice had improved survival compared to control mice. The other fourth showed no improvement.

The treated mice had less weight loss and better righting reflexes, walking ability, and forelimb grip strength than mice that did not receive TSA. Examination showed that the TSA-treated mice also had larger neurons in the spinal cord, thicker muscle fibers, and more muscle mass than untreated mice.

"This is a proof-of-concept experiment," says Dr. Sumner. "It clearly demonstrates that this treatment can ameliorate the disease in mice." While the results are exciting, there are still no stud
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