Huntington's disease: excitement as trial shows drug could slow down progression

The results were hailed as 'enormously significant' as it is the first time any drug has been shown to suppress the effects of the disease’s mutation

(Photo: BBC)
(Photo: BBC)

A Huntington’s disease trial has shown positive results, suggesting that an experimental drug could become the first to slow the progression of the genetic illness.

The results were hailed as “enormously significant” as it is the first time any drug has been shown to suppress the effects of the disease’s mutation, which causes irreversible damage to the brain.

Current available treatments only help the symptoms, rather than slow down the progression.

Director of the University College London’s Huntington Disease Centre, prof Sarah Tabrizi, who led the phase 1 trial, said that the results were “beyond what I’d ever hoped… The results of this trial are of ground-breaking importance for Huntington’s disease patients and families,” she said.

The results caused ripples across the scientific world as the drug, which is a synthetic strand of DNA, could potentially be adapted to target the incurable brain disorders such as Alzheimer’s and Parkinson’s.

The Swiss pharmaceutical giant Roche paid a $45 million license fee to take the drug forward to clinical use.

Huntington’s is an incurable degenerative disease caused by a single gene defect.

The first symptoms, which typically appear in middle age, typically include anger, depression and mood swings.

Patients then develop uncontrolled jerky movements, dementia and ultimately paralysis.

The symptoms of Huntington's disease (Photo: SlideShare)
The symptoms of Huntington's disease (Photo: SlideShare)

“Most of our patients know what’s in their future,” said Ed Wild, a UCL scientist and consultant neurologist at the National Hospital for Neurology and Neurosurgery in London, who administered the drug in the trial.

The mutant Huntington’s gene has instructions for cells to create the toxic protein called huntingtin. The code is copied by a messenger molecule and dispatched to the cell’s protein making machinery.

The drug, Ionis-HTTRx, works by intercepting the messenger molecule and destroying it before the harmful protein can be made, effectively silencing the effects of the mutant gene.

To deliver the drug to the brain, it must be injected into the fluid around the spine using a needle.

Neuroscientist at UCL, Prof John Hardy said: “If I’d have been asked five years ago if this could work, I would have absolutely said no. The fact that it does work is really remarkable.”

The trial

The trial involved 46 people with early stage Huntington’s disease in the UK, Canada and Germany.

The patients were given four spinal injections one month apart, with an increased drug dose each time. Roughly a quarter of participants had a placebo injection.

After being administered the drug, the concentration of harmful protein in the spinal cord fluid was seen to drop significantly and in proportion with the strength of the dose.

“For the first time a drug has lowered the level of the toxic disease-causing protein in the nervous system, and the drug was safe and well-tolerated,” said Tabrizi.

“This is probably the most significant moment in the history of Huntington’s since the gene [was isolated].”

The trial was small and short and therefore could not aptly show whether patients’ clinical symptoms improved, but Roche is now expected to launch a major trial aimed at testing this.

If the future trial is also successful, Tabrizi believes the drug could be used in people who have the gene, before they become ill, possibly stopping the symptoms before they even begin.

“They may just need a pulse every three to four months,” she said. “One day we want to prevent the disease.”

The drug, which was developed by the California biotech firm Ionis Pharmaceuticals, is a synthetic strand of DNA, customized to latch on to the huntingtin messenger molecule.

The success raises the possibility that a similar approach may even work for other degenerative brain disorders.

“The drug’s like Lego,” said Wild. “You can target any protein.”

“Huntington’s alone is exciting enough,” said Hardy, who first proposed that amyloid proteins play a central role in Alzheimer’s disease.

“I don’t want to overstate this too much, but if it works for one, why cant it work for a lot of them? I am very, very excited,” he said.