International gene 'silencing' trial gives hope for Huntington's disease patients

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Neurology specialists in Southampton are taking part in a potentially ground-breaking study to slow the progression of Huntington’s disease by ‘silencing’ the faulty gene which causes the serious brain disorder.

Huntington’s disease patients at Southampton General Hospital are being offered the opportunity to take part in the Generation HD1 study which aims to slow the progression of the disease by targeting the gene that causes it.

Using a pioneering ‘gene silencing’ drug that is given to patients via an injection into the spine, the study follows on from a previous, smaller scale trial which showed promising results. The study team hope the drug will dampen down the effects of the faulty gene to slow, or even halt, the progression of the disease.

Preventing progression

Huntington’s disease can cause a wide range of symptoms involving the motor system – such as uncontrollable muscle movements – and affect mood and behaviour. Over time, someone with the condition may also develop memory loss and difficulty speaking and swallowing.

Those born with the faulty gene, that results in parts of the brain becoming gradually damaged over time, are destined to develop the disease later in life, usually around 30-50 years old. There is currently no cure for the disease or any way to stop it getting worse, but treatment can help control some of the symptoms.

“Huntington’s disease is inherited from a person’s parents. Because it’s genetic, most patients living with it will have seen their parents or other family members go through the same thing,” explains Sue Jackson, a research sister for neurology and co-lead research nurse for the study in Southampton.

Targeting the genetic cause

The drug being trialled in this study, composed of antisense oligonucleotides, works by stopping the production of the Huntingtin protein from the faulty gene to prevent its damaging effects.

“Whilst this drug has been tested over the last couple of years and has shown promising results, this study is on a much larger scale and will involve over 600 patients,” says Dr Christopher Kipps, a neurologist based at University Hospital Southampton NHS Foundation Trust and  lead for the Southampton-arm of the study.

“It will take place over the next two years and will help clinicians to better understand how effective the drug is at reducing Huntingtin protein levels in the brain and, in turn, hopefully limiting or reducing the long term motor, psychological and psychiatric effects of the disease.”

All patients taking part in the trial will have a lumbar puncture every two months – either receiving the drug or a placebo. Of these patients, one group with have the drug each time, a second will receive it every four months, and the third group will only receive the placebo treatment.

Participants will also have regular MRI scans to determine whether the treatment can prevent the loss of brain tissue usually seen as the disease progresses.

“The first phase of this study was hugely informative in terms of building our understanding. Even though the faulty gene was discovered 25 years ago and there is still no effective treatment for the disease,” explains Sue.

“If this drug is as successful as we hope and is proven to slows disease progression, then it could make a massive difference to people with the condition. This study could represent a major treatment breakthrough for people who inherit this debilitating disease.”

Posted on Monday 1 July 2019