Mary* faced a tough decision: Should she undergo an extensive brain surgery as part of patient research to see whether a new gene therapy could keep her existing Huntington’s disease symptoms from worsening?
The catch?
She wouldn’t find out for a year whether she actually received the gene therapy during that 14-hour operation (nor would VCU, which is taking part in the clinical trial). At the same time, gene therapy becomes a permanent part of a patient’s DNA, unlike when an individual can stop taking a drug in a pharmaceutical trial. Those who consent to the surgery accept both potential rewards and risks of the treatment.
Mary chose to participate in the gene therapy trial.
As she waited for official word over the next 12 months, the Virginia mom said her symptoms of Huntington’s disease (HD) remained stable. While a rash of intense migraines followed shortly after the surgery, those headaches quickly dissipated, and the brief jerking movements she experienced because of the genetic disease remained unchanged — perhaps suggesting the progression of her disease had slowed.
HD is a hereditary disease that progressively destroys brain cells. As the disease advances, individuals living with HD experience difficulties in controlling their movements, as well as face issues with cognition and personality. Most patients begin to experience symptoms in their 30s or 40s.
While studies elsewhere are looking for a cure for HD, this VCU Parkinson’s and Movement Disorders Center trial is assessing whether a novel gene therapy can stop symptoms from progressing.
“When I first heard about this study, I thought it was crazy and that I never would do it,” said Mary, who is in her mid-40s. She’d participated in earlier research for a drug therapy that proved ineffective. “But what drove me to want to do this study was my own research that I did on the gene therapy. I was drawn to the fact that it could actually address things like my symptoms straight on, compared to a Band-Aid on the issue.”
Can HD be stopped in its tracks?
VCU is among several academic research hospitals participating in uniQure’s trial of an investigational gene therapy known as AMT-130. Its two key components are a vector, which acts as a delivery system, and microRNA (miRNA), small pieces of genetic material that will recognize, bind and “non-selectively” lower the human protein that causes HD. That untargeted approach means that both the normal huntingtin protein (HTT) and its disease-causing mutant (MHTT) will decrease. The trial includes study of both low- and high-dosed components.
Heather Ward, B.S., a senior clinical research coordinator in the VCU Parkinson’s and Movement Disorders Center, notes HD patients nationwide “are desperate for effective treatments,” and she fields regular calls from patients or family members wanting in on the trial. Even after learning the risks, of which death is a possibility, “they are willing to take the chance,” Ward says. Nationwide, 26 patients have participated in the AMT-130 trial, with 12 in the low-dose cohort and 14 in the high-dose one.
Mary said the prospects of participating were scary and intimidating, “but the surgery was my chance to possibly change my disease projection,’” she said.
After recovering for several days at her mother’s house and away from her preschooler after surgery, Mary was back to work full-time within two weeks.
When Mary was born, the family didn’t know HD was a hereditary disease. Her father died from HD when he was 50, and she was only 18. Eventually, she and her brother were tested and confirmed to have the disorder; her niece has more-advanced case of HD.
“I’m lucky to be able to do what I do,” said Mary, who still drives and handles full-time mom duties. She and her husband are building a new house with disability features to use should her symptoms worsen. “I’ve always lived my life knowing this was a possibility.”
Improving the moments with HD
Chris Hickok, 40, also sought to participate in the uniQure gene therapy trial. While he didn’t meet the criteria for the study, he was a candidate for a new drug aimed at easing the cognitive impacts of HD. “Sometimes I have issues where I can’t find the right word. Or I just say it wrong, or I forget what it is I’m reading about,” he said.
The clinical trial Hickok is participating in is studying how the Sage Therapeutics investigational drug, SAGE-718, might improve cognitive symptoms including impaired judgment, forgetfulness, difficulty paying attention and trouble thinking through multiple steps of an activity or complex problems.
Raised by his grandparents, Hickok learned later in his life that his father had HD. He was already in the U.S. Navy when he decided to get tested. “I could already feel balance issues and memory loss, and just sometimes getting really mad,” he said, noting that he also needed more time to complete all the paperwork that crossed his desk each day at work.
Delays in trying to get tested for HD almost prompted him to abandon the quest for a diagnosis. If only one parent has HD, then each child has a 50% chance of inheriting the genetic disorder.
Finally, after getting testing and waiting two months for results, Hickok received his diagnosis. In March, he retired from the from the military career he loved, though he is now trying to navigate the maze of securing compassionate allowance from the Navy for his HD.
At retirement, he also was three months into the Sage Therapeutics trial, traveling from his home in Suffolk for research appointments.
“My cognition is better when it comes to some stuff, and I feel like I am remembering some things a little bit more,” he said. “I don’t quite know how to say it, but I definitely feel more myself.”
“Our team is committed to participating in clinical trials of therapies that halt or significantly slow the worsening of Huntington’s disease,” says Matthew Barrett, M.D., an associate professor in the Department of Neurology’s Division of Movement Disorders. He serves as principal investigator on the AMT-130 and SAGE-178 trials. In the SAGE trial, he is joined by assistant professor Stephanie Bissonnette, DO, as sub-investigator. “Until these therapies are available, we will also be involved in research to identify better treatments for symptoms associated with the disease,” he says.
Hickok, who has two children with his wife, Lucy, feels blessed to be in the study. “I worry about my kids having this disease,” he said, “and I want there to be more progress by the time they get to be adults.”
For patients, VCU’s Ward says, participating in clinical trials is not just for extending their own lives, but the lives of their own children and family members at risk of the genetic condition.
“Some patients are really desperate to find a cure, but they're also in it to find a cure for their children and grandchildren,” she says. “They know it’s not just for them — they want to be part of the research, which is why we offer as much of these clinical trial opportunities as we can.”
*Note: “Mary” is a real patient who asked only to have her name changed. She consented to sharing her story.