A team of researchers based at Ohio State University, USA, have used gene therapy to restore nerve and muscle function and prolong life in mice with a form of spinal muscular atrophy (SMA), a lethal childhood muscle-wasting disorder. Results from the study, published in the journal Nature Biotechnology, were so encouraging that the researchers hope to progress to human trials within two years.
SMA is caused by a fault in a gene known as survival motor neuron 1 (SMN1). The mice in this study were genetically engineered to lack the SMN1 gene so that they developed a condition mimicking human SMA. A modified virus was then used to transport a working version of the SMN1 gene into the cells of the newborn mice. This restarted normal production of the SMN protein, restoring muscle coordination and normal electrical signalling in the muscles. It also dramatically increased the lifespan of the mice allowing them to live over 16 times longer than untreated mice.
The therapy offers a one off treatment to restore the body to normal functioning, giving it an advantage over current experimental drug treatments, which would require a lifetime of medication, according to Professor Arthur Burghes, one of the study's leaders. 'This technique corrects the mice considerably more than any drug cocktails being studied as a potential treatment in humans,' he told the Times.
Infants born with the most severe form of SMA develop paralysis, in some cases becoming so severe they can no longer lift their heads. Children can die before the age of two, often due to respiratory problems. The incurable disease affects up to one in 6000 babies and kills about 50 infants in the UK every year.
Trials on monkeys have shown further promise, but researchers will need to establish it is safe and also determine how early in the patient's life it must be administered, before it can be made available for human use. Furthermore, the symptoms of SMA aren't always apparent at birth, so a newborn screening programme may be necessary to be able to detect the condition early enough for the treatment to work.
Alex MacKenzie, a SMA researcher at the University of Ottawa, Canada, told the Times 'This study combined with the possibility of disease screening in newborns, raises, for the first time, hope of real therapeutic progress against this as yet untreatable disorder'.
Scientists have been cautious about gene therapy since setbacks in early trials, including the death of 18 year old Jesse Gelsinger during a gene therapy trial in 1999. But with safer and more effective approaches now being developed, there is fresh optimism that gene therapy could become a valuable treatment approach for certain single gene disorders, particularly those which are life limiting and have no other treatment options.