Isis Pharmaceutical trials have begun for a much-anticipated antisense drug, ISIS-HTTRx,. ISIS-HTTRx, aims to reduce the amount of mutant huntingtin protein made in the brain. The antisense oglionucleotide drug binds to the mRNA of the harmful huntingtin protein and physically prevents protein production. The drug also recruits an enzyme to degrade the mRNA. (For more information about antisense gene therapy, please see this article.) ISIS-HTTRx, is the first therapy to reach clinical development that targets the production of huntingtin protein.
The 1/2a study is designed to test the safety and tolerability of multiple doses of the drug in adult patients with early manifest HD. Each dose will be administered through a lower back injection, commonly known as a lumbar puncture or ‘spinal tap.’ During this procedure, a needle is inserted between two vertebrae in your lower back and the drug is injected. The study will be randomized so that 75% of the patients will receive ISIS-HTTRx,, and 25% will receive a placebo. This randomization will allow the study to meet the statistical standards required to assess drug safety.
The pharmaceutical trial will enroll 36 patients who pass the additional screening evaluations, and will take place at six centers in Canada, the United Kingdom, and Germany. Only patients who live within four hours ground-travel distance of a study center will be eligible. If the study finds that the drug is safe and well tolerated, further trials will be needed to test for its effectiveness in treating symptoms. Future clinical trials will likely include testing sites in the U.S.