Antisense Gene Therapy Corrects Spinal Muscular Atrophy

SMA affects from 1 in 6,000 to 1 in 10,000 children born each year, and 1 in 40 are carriers of the disease.

Investigators from Iowa State University (Ames, USA) worked with cultures of cells obtained from SMA victims. These cells carried both the mutated form of the SMN1 (survival motor neuron 1) gene and the ineffective form of the SMN2 gene. Neither of these two genes was capable of synthesizing SMN protein, lack of which causes SMA.

In a study published in the July 1, 2009, online edition of the journal RNA Biology, the investigators described a method for correcting SMA by treating the cells with a small antisense oligonucleotide directed at the SMN2 gene. The nucleotide bound and blocked a "junk DNA” codon on the SMN2 gene, a situation that enabled RNA binding and subsequent synthesis of SMN protein. The amount of SMN protein that was made was enough to reverse the effects of the disease.

"The significance of our work is that we have this stuff called junk DNA in SMN2,” said senior author Dr. Ravindra Singh, associate professor of biomedical sciences at Iowa State University. "We found that we could get SMN2 to behave as SMN1 by introducing a small oligonucleotide. It is a very simple experiment if you think about it. Our cells are healthy and survive. From that point of view, this is a major achievement. If this is a model disease, meaning we succeed in treating SMA, we will know how to correct splicing of other genes in other diseases. We know that Parkinson's disease, Alzheimer's disease, cystic fibrosis, multiple sclerosis, and cancer all come from genes that are aberrantly spliced.”

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