Huntington's Disease, a fatal inherited degenerative brain condition, can be controlled in animals using DNA technology, suggesting it might be reversible in humans too.
Huntington's, which affects about 1 person in ten thousand, is a genetically-transmitted disease of the nervous system that leads to behavioural changes and abnormal movements. These symptoms usually begin after the age of 40.
The nervous systems of sufferers show loss of grey matter, with the brain shrinking by up to a third of its volume once the disease has run its course.
The cause of this degeneration appears to be the accumulation inside nerve cells of a substance called polyglutamine. This occurs because, in carriers of the condition, the gene linked to Huntington's - called huntingtin - contains a repeating sequence of three genetic letters - CAG - that has been abnormally duplicated, making it much longer than it should be.
Repeated CAG signatures like this tell a cell to link glutamine molecules together; unfortunately these glutamine chains are then not easily disposed of, so they inexorably accumulate within the cell with ultimately toxic effect.
But now a paper in the journal Neuron has shown that the application of a technology that won a recent Nobel prize - RNA interference - to the problem can potentially arrest the disease.
University of California San Diego scientist Don Cleveland and his colleagues have been working with mice endowed with a copy of the abnormal human Huntington's gene.
These animals manifest a similar degenerative disease to human sufferers, developing abnormal movements and behavioural deficits from a young age.
The UCSD team constructed and infused into the cerebrospinal fluid around the brains of these animals an RNA sequence that is the genetic mirror image of part of the Huntington's gene. When taken up by cells, these short pieces of genetic material pair up with the products of their matching gene, in this case the huntingtin gene, and cause the genetic message to be shut off so the gene is not expressed.
When administered to the test animals over a two week period, the therapeutic genetic sequences produced a 75% reduction in the levels of expression of the abnormal gene and an improvement in symptoms and disease progression that was still measurable months later.
Tests on a rhesus monkey also suggest that the approach could be delivered to humans using a spinal cannula like that employed to deliver epidural pain relief during labour.
Concluding their paper, the researchers point out that "transient suppression of huntingtin can be sufficient to ameliorate disease for an extended period of time... this finding opens up the provocative possibility that transient suppression of huntingtin can lead to a prolonged effect in patients."