Genetic hit for motor neurone disease

Oxford BioMedica develops new gene therapy product.

Scientists from Oxford BioMedica, a UK biopharmaceutical company, claim to be well on the way to discovering a treatment for the most prevalent form of motor neurone disease (MND), amyotrophic lateral sclerosis (ALS). Together with researchers from Flanders University, Leuven, Belgium, they have developed a novel gene therapy product called MoNuDin.

MND causes motor neurones, the nerve cells which the brain uses to send signals to the muscles, to degenerate leading to weakness and muscle wastage. According to the Motor Neurone Disease Association, three people die from MND in the UK every day and the disease affects more than 5000 people at any one time. MND is still incurable, generally resulting in paralysis and death three to five years after onset.

There is strong evidence to back suggestions that the disease is linked to reduced levels of vascular endothelial growth factor (VEGF). This polypeptide is essential in angiogenesis, the growth and proliferation of blood cells, and is also thought to have neuroprotective qualities.

Oxford BioMedica’s new product delivers a VEGF gene using a lentiviral gene transfer system (which is based on an equine anaemia virus). The product is injected into muscle and then works within the spine’s nerve cells.

The researchers tested their product on mice which had been engineered to overexpress a gene that has been linked to ALS called SOD1. They discovered that a single injection of MoNuDin delayed onset and slowed progression of ALS and in a paper in Nature claim that it increased the life expectancy of ALS mice by 30 per cent without causing toxic side effects. The team found that the gene treatment was effective even when delivered after the disease was in a fairly advanced state. This is important because in most cases ALS cannot be diagnosed before onset of the disease.

The researchers believe that their system ’may have potential as a safe and practical treatment for many of the motor symptoms of human ALS’.

Although the results are still at a preclinical stage, Alan Kingsman, Oxford BioMedica’s chief executive, considers that they suggest that ’VEGF gene therapy could provide an effective treatment for ALS’. The results also ’bode well’ for Oxford BioMedica’s spinal muscular atrophy product which employs a similar technology, he said.

Margaret Lowrie, from the Division of Biomedical Sciences at Imperial College London, described the work as interesting but urged caution. She told Chemistry World: ’It is too early to say how useful it could be for MND because we still don’t know what causes it. Only about 2 per cent of cases carry the SOD mutation and most cases are non-familial. Furthermore, the SOD mouse has not been studied comprehensively from a physiological point of view.’

Emma Davies