In December 2017, a California company called Ionis released its preliminary results from a small Huntington’s disease study. These results have yet to be published or reported at medical meetings, but the findings so far are promising. They’ve developed a drug, called an antisense oligonucleotide, that reduced the production of an abnormal version of the huntingtin protein that could cause the disease.
Every four weeks for three months, 46 people from the United Kingdom, Germany, and Canada received an injection—of either the drug or a placebo—into their spinal fluid. Three to four months after their final dose, they returned to the lab for tests. The researchers then tallied up how much of the mutated huntingtin protein was present and found a reduced amount of protein in people who received the drug.
These results came as a surprise. While trials are often successful in Petri dishes or mice, it’s less common for human trials to be as promising. Here’s Esther Landhuis, reporting for Scientific American:
Neuroscientist John Hardy, a University College London colleague not involved in the study, found the results a complete surprise. “It’s all very well to give antisense therapies to a mouse with a 300-milligram brain,” he says. “But to give spinal fluid injections [in people] and have it spread through the brain to an extent great enough to knock down gene expression….” He adds: “Three or four years ago, I would not have expected that to work, and yet it does. This could be a whole new generally applicable type of drug.”
Huntington’s disease is a neurodegenerative disease—and like, Lou Gehrig’s, Parkinson’s, and Alzheimer’s, it has no cure. Symptoms like involuntary movement, slowness in speech or thinking, start appearing after a person’s 30th birthday. It’s an inheritable disease that can be traced to repetitions in a gene known as HTT. The brain cells convert this mutation into the protein that is thought to drive Huntington’s.
That’s where Ionis’s therapy comes in. Unlike other drugs, which target the symptoms, the company’s drug binds to RNA, which translates genes into proteins, and blocks the final set of instructions for making huntingtin.
While the results have been promising, there’s more work to be done before it becomes widely available. Researchers will need to conduct a larger trial, on the order of hundreds of patients, to see if lowering HTT slows the progression of Huntington’s disease. Then they would trial healthy people with the HTT mutation to see if antisense drugs could prevent it altogether.
This isn’t the first time an antisense drug has helped fight against disease. Two studies focusing on spinal muscular atrophy, an inherited neuromuscular disorder in children, were stopped in 2016 after kids taking the drug showed motor improvements so vast that it became unethical to keep giving other kids the placebo. Later that year, the U.S. Food and Drug Administration approved the drug.