Gene silencing drug shows promise against Huntington’s disease

The breakthrough drug could "slow or prevent" the previously incurable hereditary disease


In December, researchers at University College London revealed that they had made a breakthrough in drug trials showing the potential to stop the previously incurable hereditary condition Huntington’s disease. The drug, Ionis-HTTRx, operates by gene silencing and can lower the amount of toxic proteins in the brain, preventing neurodegeneration – the death of cells in the brain.

Many experts have described it as the biggest breakthrough in 50 years for neurodegenerative diseases. With 8,500 people in the UK suffering from Huntington’s disease, the new drug is a large step towards a potential cure. It also provides hope for treating similar conditions such as dementia and Parkinson’s disease.

Huntington’s disease is a genetic condition that affects 1 in 10,000 people in Western countries. On average, the effects appear between the ages of 30 and 50, but it can also affect younger people. The symptoms are caused by the build-up of a toxic protein known as mutant Huntingtin. The mutant protein is formed by having an excess number of repeats of glutamines within the Huntingtin gene on chromosome 4. The protein aggregates in neurons, resulting in cell death. This manifests into symptoms that affect the central nervous system including problems with movement, mood and cognition, gradually leading to death.

Moreover, the gene for Huntington’s is autosomal dominant, which means that you only need to inherit one copy of the gene from one parent to present the symptoms. It is predicted 25,000 people will suffer from Huntington’s disease in the UK in the next generation due to the 50% likelihood of it being inherited. For this reason, research into treatments has been essential.

The drug, Ionis-HTTRx, has been found to lower the amount of Huntingtin. The drug is structurally similar to DNA, being composed of antisense oligosaccharides. It operates by effectively ‘shooting the messenger’ that leads to the formation of the protein – because Ionis is similar to the Huntingtin gene, the mRNA that would normally create the toxic Huntingtin protein binds strongly to it, becoming inactive.

The drug was injected into the spinal fluid of 46 patients at the National Hospital for Neurology and Neurosurgery in London. The treatment was tolerated by the patients and significantly lowered the amount of toxic Huntingtin protein produced. The BBC interviewed Prof Sarah Tabrizi, the lead researcher of Huntington’s disease at UCL, who suggested that “the therapy one day may slow or prevent Huntington’s disease” and that the news is of “ground-breaking importance for patients and families”. It is hoped the drug can be refined and improved to be used to treat Huntington’s disease in the future.

Furthermore, similar proteins to Huntingtin are associated with the symptoms of dementia and Parkinson’s disease. For this reason, researchers hope a similar approach may be used to silence synuclein, involved in Parkinson’s disease, and amyloid and tau, for dementia. However, these proteins are less well researched.

850,000 people suffer from dementia, costing the NHS £26 billion a year. Through further research and combining the knowledge of geneticists and pharmaceutical experts, it is hoped more lives could be saved and pressures on the national health service will be reduced.