Vitamin Deficiencies May Worsen SMA

A new study suggests that people with the disease spinal muscular atrophy (SMA) should have their diets carefully monitored to ensure they're getting adequate levels of the vitamins folate and vitamin B12.

SMA involves the progressive death of muscle-controlling nerve cells (motor neurons) in the spinal cord, and is caused by genetic deficiencies of a protein called SMN (survival motor neuron). The new study shows that the activity of SMN depends on folate and vitamin B12, which means that insufficient levels of the two vitamins might magnify the effects of SMN deficiency and hasten the course of SMA.

"It would be advisable for [SMA] patients to consult their doctors to see that they're getting at least the recommended daily dose of these vitamins, but we're not suggesting that people rush out and take them," said the new study's lead scientist, Gideon Dreyfuss, a molecular biologist at the University of Pennsylvania in Philadelphia.

Dreyfuss also said it's possible that, for some people, using folate and vitamin B12 as nutritional supplements might help ameliorate the muscle weakness and wasting caused by SMA. It's not known if people with severe SMA tend to have low levels of folate or vitamin B12, or if people with SMA who have normal levels of the vitamins would benefit from taking more.

"Clinical trials have not yet been performed, so I don't want to raise any false hopes that this is a cure or that it will definitely make people better," he said. "Mostly, we're suggesting an alert that people [with SMA]...make sure they don't have deficiencies in these vitamins."

Dreyfuss' new findings add to several years of research he's spent deciphering the functions of the SMN protein. SMN, he's shown, is required for putting the finishing touches on RNA — an essential intermediate between DNA (the material that makes up genes) and protein.

To perform its job, SMN has to work with several other proteins, and, in his latest study, Dreyfuss found that SMN is more likely to recognize those proteins when they carry a chemical "tag" called a methyl group. Previous research has shown that methylation — the process of sticking a methyl group onto a protein — requires folate and vitamin B12. So the two vitamins are probably critical to SMN's normal function, and could be especially important in someone with SMA.

For his study, which appears in the May 25 issue of Molecular Cell, Dreyfuss examined laboratory cell lines and biochemically isolated proteins — not people with SMA.

"We speculate that if [SMA] patients are deficient in folate and B12, that will cause their proteins to be under-methylated and could perhaps cause their disease to be more severe," Dreyfuss said. "This hasn't been tested in humans, so we don't really know."

Dreyfuss added that he and other researchers are planning a clinical trial to determine if dietary intake of folate and vitamin B12 actually influence the course of SMA.