The first human trial of an experimental drug designed to combat Huntington’s disease has delivered a success beyond what the researchers themselves hoped for.
Results from a clinical trial involving 46 patients with early Huntington’s shows that an injectable drug called IONIS-HTTRx successfully lowered levels of the harmful huntingtin protein in the participants’ nervous system.
“The results of this trial are of ground-breaking importance for Huntington’s disease patients and families,” says neurologist Sarah Tabrizi from University College London’s Huntington’s Disease Centre, which led the trial.
“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.”
The drug, which is administered by injection into the spinal fluid in order to reach the brain, has been in development for more than a decade, but until now researchers didn’t know exactly how IONIS-HTTRx would impact the toxic huntingtin protein in humans.
Huntington’s disease is a progressive brain disorder that causes uncontrolled movements, emotional problems, and cognitive impairment, leading to dementia and early death in most people who develop the condition.
The disease is caused by a mutation in the Huntingtin (HTT) gene, which produces the huntingtin protein – but the genetic variant ends up making abnormally long versions of this protein, which divide into toxic fragments than can bind to and impede neurons.
IONIS-HTTRx is an antisense drug, which aims to effectively silence the Huntingtin gene and prevent the production of the harmful form of the huntingtin protein.
In the trial, patients who received increasing doses of IONIS-HTTRx over the course of the study exhibited lower levels of huntingtin protein concentration in their spinal fluid after they received the treatment.
It’s the first time the toxic protein has been successfully lowered in patients’ nervous systems, signalling what could be the foundations of the first working treatment for Huntington’s – and giving fresh hope to thousands of people around the world with the condition.
“This is probably the most significant moment in the history of Huntington’s since the gene [was isolated],” Tabrizi told The Guardian.
Of course, as promising as these results are, it’s early days yet. The researchers intend to formally present and publish their findings next year, but the bigger question remains whether IONIS-HTTRx can also mitigate the symptoms of Huntington’s disease, which hasn’t yet been assessed at this stage of the trials.
That’s the next step for the team and the drug’s maker – California biotech firm Ionis Pharmaceuticals – who now intend to move to larger tests to examine how the injections may slow disease progression.
There’s a lot on the line here. If future clinical trials deliver signs as promising as these early results, the researchers say occasional IONIS-HTTRx injections might one day be able to prevent people with Huntington’s from ever getting sick or showing symptoms of their condition.
Beyond Huntington’s, researchers think the early success of IONIS-HTTRx shows just how powerful gene-silencing medicine has become, meaning we’re closer than ever to potential treatments for other genetic conditions, such as Alzheimer’sand Parkinson’s disease.
“This is a potential game-changer, not only for Huntington’s disease patients but also for genomic medicine in general,” says molecular biologist Philippa Brice from health science nonprofit, the PHG Foundation, who wasn’t involved in the research.
“Though more work needs to be done, if gene silencing lives up to this promise we could be on the brink of some of the personalised treatments that patients with severe genetic diseases need so badly.”