The data shows that the new gene therapy and gene silencing treatment slows the disease by 75%!

Huntington’s disease is a genetic disorder that is caused by the inheritance of a dominant allele (OCR(A) & AQA) . A mutation occurs in the HTT gene (Huntingtin gene) that results in more CAG repeats. Once over a threshold number of 40 repeats, the huntingtin protein will be made with an altered structure. The protein becomes non-functional. This non-functional protein affects the phenotype by causing the destruction of neurones resulting in a cognitive decline. Other symptoms include behavioural, personality and mood changes, as well as coordination and movement difficulties. The condition is degenerative. This example clearly demonstrates the relationship between genes, proteins and phenotypes.

Because of the dominant nature of this disease, it means that people who are heterozygous will have symptoms as only one dominant allele is needed to be expressed to get the faulty protein. The symptoms only become present later on during life (30s to 40s) and so most people will have already had children before they know they have the disease. There is then a 50% chance that the child will have inherited the dominant allele.

Dominant genetic diseases have been challenging to treat via gene therapy (OCR(A) & AQA) because in the past the only option was to add a functional allele to treat recessive diseases. It hasn’t been possible to remove or silence a dominant allele.

The gene therapy treatment involves RNA interference (RNAi) (AQA). A type of RNAi called microRNA (miRNA) is designed to be complementary to and bind to the mRNA produced from the transcription of the HTT gene. Now the mRNA is bound to the miRNA, it cannot bind to a ribosome. The gene is effectively silenced as no translation of the mRNA can now take place. Less harmful faulty Huntingtin protein is made so there is less damage to neurones.

A safe virus contains the specific DNA sequence, that when transcribed makes the required miRNA. The virus is infused deep into specific parts deep in the brain. The neurones take up this DNA and carry out transcription in the normal way to make the miRNA. With less faulty huntingtin being made, the damage to neurones is reduced. This is an expensive treatment involving 12 to 18 hours of expert brain surgery.

It is still at the trial stage which involved 29 patients. The data shows that there was a slowing down of symptoms three years after the surgery. If this were an evaluation exam question, we would be wanting to see a larger sample size to be representative of the whole population and a longer study to see the longer-term effects. As this trial progresses – I am sure we will get to see this!

Download the article from the BBC news page here