Huntington’s Drug That Silences Gene at Root of Disease Now in Phase 1 Clinical Test

A drug targeting the cause of Huntington’s disease (HD) was found effective and safe in animal tests, and clinical studies in humans are beginning, according to newly released data that will be presented at the American Academy of Neurology‘s 68th Annual Meeting in Vancouver, Canada, on April 15–21, 2016.

The drug, IONIS-HTTRx, is a so-called antisense drug that inhibits the expression of the huntingtin gene and therefore reduces the production of huntingtin protein in patients with HD. “It is very exciting to have the possibility of a treatment that could alter the course of this devastating disease,” Blair R. Leavitt, the study’s principal investigator from the University of British Columbia in Vancouver, said in a press release. “Right now we only have treatments that work on the symptoms of the disease.” Leavitt added that the drug is still a far cry away from being applied in routine clinical practice.

Early studies found that animal models of HD treated with antisense drugs showed slower disease progression and demonstrated a sustained reversal of the disease phenotype.

In transgenic mouse models of HD (YAC128 mice), motor deficits started to improve a few weeks after the antisense treatment and normal levels were achieved two months after treatment termination. Another transgenic mouse model of HD (BACHD mice) showed improved motor skills in eight weeks after the initiation of antisense drug treatment, which lasted for a minimum of nine months after treatment termination.

In monkeys, reduction of HTT mRNA and Htt protein levels in the central nervous system was found after treatment with the antisense drug in a dose-dependent manner. Further studies of IONIS-HTTRx in rodents and monkeys revealed that the antisense drug was well-tolerated lacking any dose-limiting side effects.

The drug, currently in Phase 1/2a clinical trials, is administered into the cerebral spinal fluid through an intrathecal injection on the lumbar space, since antisense drugs cannot cross the blood-brain barrier. The current clinical study will evaluate the drug’s safety and tolerability, in addition to its pharmacokinetic characterization, in ascending doses. The drug’s effects on specific biomarkers and overall clinical outcomes will also be investigated.

Ionis Pharmaceuticals in collaboration with CHDI Foundation, Roche Pharmaceuticals and University of California, San Diego, developed the antisense drug. The preclinical studies were conducted by Ionis Pharmaceuticals and the clinical study is supported by Ionis Pharmaceuticals and, partly, by Roche Pharmaceuticals.

More information on the clinical trial now getting underway in Canada, Germany, and the United Kingdom is available at its clinical trials.gov site (NCT02519036).