The first human drug for Huntington's disease is safe and effective in mice and monkeys

The first drug that directly targets the cause of Huntington’s disease (HD) has been found safe and effective in tests in mice and monkeys, according to results to be presented April 16, 2016 at the American Academy of Neurology’s (AAN) annual meeting in Vancouver, Canada.

Based on these animal studies, researchers have begun a clinical trial to test the drug in humans with Huntington’s disease.

“It is very exciting to have the possibility of a treatment that could alter the course of this devastating disease,” said clinical study principal investigator Blair R. Leavitt, MD, of the University of British Columbia in Vancouver, who will present the results at the upcoming AAN meeting’s plenary session. “Right now we only have treatments that work on the symptoms of the disease.”

The new drug, IONIS-HTTRx, is an antisense drug—a “gene silencer”—that targets HTT mRNA to inhibit production of the huntingtin protein, produced by the HTT gene. Because antisense drugs can’t cross the blood-brain barrier, IONIS-HTTRx has to be delivered into the cerebrospinal fluid by injection into the lumbar space once a month for 4 months.

In the animal studies, the drug was not only well tolerated with no dose-limiting side effects, but it delayed disease progression and reversed the disease phenotype. In one transgenic mouse model, the drug improved motor skills in 8 weeks—an effect that continued for at least 9 months after the drug was stopped.

The researchers administered the drug in monkeys the same way as in humans, and found that it reduced HTT mRNA and Htt protein throughout the central nervous system in a dose-dependent manner. The drug lowered cortical huntingtin levels by 50% in the monkeys, which correlated with a 15% to 20% reduction in the caudate nucleus.

Guided by these animal studies, the researchers announced in 2015 that they had begun a phase I/IIa clinical trial of IONIS-HTTRx in human patients with Huntington’s disease.

“I’m thrilled that this antisense drug has now been safely administered to the first patients. Families ravaged by Huntington’s disease have been waiting for this milestone for decades,” said the global chief clinical investigator of the trial, Sarah Tabrizi, MBChB, PhD, Director of the Huntington’s Disease Centre at University College London’s Institute of Neurology, in London, United Kingdom.

The ongoing clinical study is supported by Ionis Pharmaceuticals, which has collaborated with Roche to develop IONIS-HTTRx.