UCL Queen Square Institute of Neurology


Drug lowers deadly Huntington’s disease protein

11 December 2017

The first drug targeting the cause of Huntington’s disease was safe and well-tolerated in its first human trial, and successfully lowered the level of the harmful huntingtin protein in the nervous system.

After over a decade in pre-clinical development, this first human trial of huntingtin-lowering drug began in late 2015, led by Professor Sarah Tabrizi (UCL Institute of Neurology) and sponsored by Ionis Pharmaceuticals.

The trial involved enrolling 46 patients with early Huntington’s disease at 9 study centres in the UK, Germany and Canada.

Each patient received four doses of either IONIS-HTTRx or placebo, given by injection into the spinal fluid to enable it to reach the brain. As the phase 1/2a trial progressed, the dose of IONIS-HTTRx was increased several times according to the ascending-dose trial design.

Patient safety was monitored throughout the study by an independent safety committee.

Today’s announcement at completion of the trial confirms that IONIS-HTTRx was well-tolerated by the trial participants and its safety profile supports further testing in patients.

“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. The key now is to move quickly to a larger trial to test whether the drug slows disease progression.” Professor Tabrizi, Director of the UCL Huntington’s Disease Centre and IONIS-HTTRx Global Chief Investigator

A major unknown was whether the trial would show that IONIS-HTTRx could lower the level of mutant huntingtin protein in the nervous system. Using an ultra-sensitive assay, concentrations of the protein were measured in each patient’s spinal fluid before and after treatment.

As hoped, IONIS-HTTRx­ produced significant, dose-dependent lowering of the level of mutant huntingtin – the first time the protein known to cause Huntington’s has been lowered in the nervous system of patients.

As a result of these successful outcomes, Ionis’ partner, Roche, has exercised its option to license IONIS-HTTRx and assumes responsibility for further development, regulatory activities and commercialization activities. Meanwhile, Ionis announced in June that all patients in the completed trial would be offered a place in an open-label extension to receive IONIS-HTTRx.

The results of the trial and plans for the ongoing IONIS-HTTRx programme will be presented in detail at forthcoming scientific meetings and prepared for peer-reviewed publication.

The research is supported by The National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research CentreThe centre is a partnership between UCL and University College London Hospitals NHS Foundation Trust funded by the NIHR to translate scientific breakthroughs into better patient treatments.

“I am delighted to see these encouraging results which, for the first time, show a clear therapy induced reduction in mutant Huntingtin in the central nervous system.  I want to congratulate Sarah Tabrizi and the entire Huntington’s Disease Centre research team at the UCL Queen Square Institute of Neurology.  These findings open a new chapter in therapy development for Huntington’s Disease. In addition this important proof of concept  study points to the huge potential of the antisense oligonucleotide approach in single gene disorders affecting the nervous system. It has clear relevance for the subset of other devastating neurodegenerative disorders including dementia, Parkinson’s disease, ataxias and neuromuscular diseases including motor neurone diseases (ALS) that are caused by single gene mutations. The unique clinical academic and translational neuroscience environment at the UCL Queen Square Institute of Neurology, including the Leonard Wolfson Experimental Neurology Centre, is the perfect setting to lead the world in this next exciting phase of antisense therapy development for patients”. Professor Michael Hanna, Director of UCL Institute of Neurology

Further information: