Two teams of researchers have successfully treated mice affected by amyotrophic lateral sclerosis (ALS), using a novel form of gene therapy. The achievement offers hope that the technique, known as RNAi (RNA interference), will lead to new therapies for a range of diseases. The scientists, based in Switzerland and the UK, both published their findings early online in the journal Nature Medicine.
ALS is a form of motor neurone disease that causes progressive, incurable paralysis. The symptoms are the result of gradual damage to motor neurones - nerve cells in the brain and spine that control movement. It affects around one in 20,000 people, including the UK astrophysicist Stephen Hawking. Most cases of ALS are not inherited, and have no known cause, but a small proportion are caused by alterations in a gene called SOD1.
In the latest studies, the researchers worked with mice genetically altered to over-produce the protein made by the faulty SOD-1 gene, thus mimicking the human version of ALS. The teams then used the RNAi technique to successfully 'damp down' SOD-1 gene activity in the mice. At the same time, they injected a working version of the gene, which produced normal amounts of the SOD-1 protein. Symptoms of ALS appeared much later in the treated animals, and extended their lifespan by nearly 80 per cent.
'This is the first proof of principle in the human form of a disease in the nervous system where you can silence the gene and at the same time produce another normal form of the protein' said Patrick Aebischer, leader of the Swiss study. As well as raising hopes for new treatments for ALS, the new approach could potentially be used to treat any disease caused by overproduction of a 'toxic' protein, rather than a missing one. 'I would not be surprised to see, in the next ten years, this technology used for treating diseases of the nervous system, such as inherited forms of Parkinson's disease or Huntington's disease', said Aebischer.
RNAi is thought to be a naturally-occurring defence mechanism against viruses, which scientists are trying to exploit as a way of selectively shutting down gene activity. The approach involves injecting cells with specific, short pieces of RNA, which then trigger the breakdown of a particular messenger RNA molecule - the intermediate stage between a gene and the protein it codes for. In this way, scientists can selectively shut down production of any protein made by the cell, without affecting any others.