Drug lowers harmful Huntington’s disease proteins in humans, according to research

Researchers from the University College London (UCL) Huntington’s Disease Centre have developed a drug that has been shown to be safe and well-tolerated in its first human trial, successfully lowering the level of harmful huntingtin protein in the nervous system.

The trial, which began in late 2015, was led by Professor Sarah Tabrizi (UCL Institute of Neurology) and sponsored by Ionis Pharmaceuticals. It involved 46 patients with early Huntington’s disease, who were treated and monitored at nine centres in the UK, Germany and Canada.

In the trial, each patient was administered with four doses of either IONIS-HTTRx or a placebo, which was injected into the spinal fluid so that it reached the brain. Progression of the trial included an increase in dose, according to the ascending-dose trial design.

Patient safety during the trial was monitored by an independent safety committee.

“The results of this trial are of ground-breaking importance for Huntington’s disease patients and families. 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, director of the UCL Huntington’s Disease Centre and IONIS-HTTRx global chief investigator. “The key now is to move quickly to a larger trial to test whether the drug slows disease progression.”

Using an ultra-sensitive assay, the researchers measured the concentrations of huntingtin protein in the nervous system in order to evaluate whether IONIS-HTTRx was capable of lowering the level. Based on the results of the trial, it was found that IONIS-HTTRx produced significant, dose-dependent lowering of the level of mutant huntingtin, which is the first time this result has been achieved in humans.

As a result of the success of this trial, Ionis’ partner Roche, has exercised its option to license IONIS-HTTRx and assumes responsibility for further development, regulatory activities and commercialisation activities.

Additionally, the trial sponsor has announced that all patients who completed the trial would be offered a place in an open-label extension to receive IONIS-HTTRx.