Bringing about a brighter future for patients and their families
Studies of nature and of human genetics have guided our approach to address repeat expansion disorders at the deepest level — halting the ongoing damage to DNA. We are working to improve the future outlook for families affected by Huntington’s disease, myotonic dystrophy and many other disorders.
We have initiated a natural history study of Huntington’s disease (HD), called SHIELD HD, to assess clinical outcomes and biomarkers that will inform planning for upcoming interventional clinical trials. SHIELD HD will enroll approximately 60 Huntington’s disease gene expansion carriers and follow them for up to two years at clinical sites in North America and Europe. The study includes both early manifest and premanifest individuals, with enrichment for premanifest subjects who have begun to show signs or symptoms. Patients and families interested in learning more about SHIELD HD should contact Triplet directly. The study is registered at ClinicalTrials.gov.
Making every moment count: Living with Huntington’s disease
On the wall above the couch is a sign that reads, “Time is precious. Waste it wisely.”
Jonathan has adopted that saying as his mantra. His father died from Huntington’s disease (HD). So did his older brother. And Jonathan has felt certain for years that he is living with HD, too. He recently turned 21 and had the genetic testing that confirmed the diagnosis.
So he knows time is precious — and he’s not wasting any of it.
Although living with HD has put his dream of joining the Navy out of reach, Jonathan remains an ardent thrill-seeker. He loves downhill skiing and gathering with his many cousins for paintball. He recently went ziplining for the first time, and bungee jumping and skydiving are at the top of his to-do list. As a passionate student of history with a particular interest in WWII, Jonathan hopes to visit Germany and Italy in the coming years.
And he has recently added another life goal: Working with the HD community to support research into new treatments.
When it comes to raising awareness for HD, he puts it simply: “I’m down for anything.”
A long family history
HD is a genetic disorder caused by a mutation in the HTT gene, which is responsible for making a protein called huntingtin that plays a role in brain development and function. Individuals with HD inherit an HTT gene with “DNA repeats” — short genetic sequences that repeat over and over — in the HTT gene. The presence of all these repeats is believed to be toxic — and wreak havoc on cells in the body, including the brain’s neurons, affecting mood, cognition and motor skills. The greater the number of inherited repeats, the greater the toxic effects, and the earlier the age that symptoms begin.
Thanks to the contributions of thousands of HD patients, whose participation in genetic research has built a fundamentally new understanding of the cause of repeat expansion disorders, we know today that the number of repeat sequences expands over time. As repeats become longer, expansion accelerates, increasing the toxic impact on cells and specifically neurons in the brain.
As a history buff, Jonathan has been over his own family tree many times and knows that HD emerged generations ago, on his father’s side. Growing up, he was aware that he might carry the HD gene.
The first symptoms emerged in high school, when Jonathan’s classmates nicknamed him “Bricks” because he ran like he had bricks in his shoes — heavily and out of control. “I know I have it,” Jonathan remembers thinking.
Jonathan’s mother, Gina, recognized the symptoms she had already lived through with her husband and elder son. “We knew, he’s just not the same kid he was,” she says. “He was always chatty. Now he’s quiet. He was always smiling. Now he doesn’t smile anymore. Or doesn’t smile nearly as much. I knew beyond a shadow of a doubt that he had it.”
HD causes the relentlessly progressive degeneration of nerve cells in the brain. Adult onset of HD generally begins in the 30s or 40s, and people typically live with the worsening disease for 10 to 20 years after diagnosis, ultimately becoming bedridden and unable to care for themselves. When symptoms begin to develop before age 20 — as with Jonathan and his older brother — the disorder is considered juvenile HD, which is characterized by longer inherited DNA repeats and greater expansion of DNA repeats in brain neurons.
“We knew, he’s just not the same kid he was. He was always chatty. Now he’s quiet. He was always smiling. Now he doesn’t smile anymore. Or doesn’t smile nearly as much. I knew beyond a shadow of a doubt that he had it.”
– Gina, Jonathan’s mother
Gina, of course, knows all of this. When she and Jonathan’s father, Patrick, met in the 1980s, they were already aware that Patrick was at risk of developing HD due to family history of the disease, but at that time, a genetic test was not available. The two of them visited a genetic counselor, who encouraged them not to have children due to the risk that Patrick would pass on the HD gene.
For Gina and Patrick, this never felt like a real option. Nodding toward the quote on the wall in her home in Dracut, Mass., Gina says, “Life is precious. That’s why we had kids. We don’t know how much time we have, and we didn’t want to waste it.”
Patrick-Anthony, their oldest son, was born into a happy family. But as he grew, his father’s symptoms worsened. Patrick started having trouble at his job. He experienced dramatic weight loss, although this didn’t immediately register as a concern. “He had been trying to lose weight — his pants were too tight,” Gina remembers. “I didn’t realize that it was the first symptom.”
Gina got pregnant again, still unaware of the severity of her husband’s troubles. On the day Jonathan was born, their family doctor came to visit Gina in her hospital room. He’d been seeing Patrick for many years, and the symptoms were clear. “He told me, ‘Gina, I know he has HD. He needs to go in to get tested,’” Gina recalls.
A feeling of isolation
Patrick’s diagnosis left Gina and Patrick feeling very much alone. “Google didn’t exist. All you could read about Huntington’s was a sentence or two that they would hand you. It told you that Huntington’s was the worst disease,” Gina says.
The next few years were tumultuous. Patrick’s HD symptoms continued to worsen. He moved out of the family’s home and into his own apartment, then later into assisted living and to hospice care. He passed away at 46 years old.
Patrick-Anthony was diagnosed at age 11. An aspiring veterinarian, he had a fiercely independent personality. “I don’t think he let anybody help him,” Gina says. Patrick-Anthony lived at home and attended school up until his death at age 13.
The quote on the wall, which Gina first learned about while attending an HD awareness walk with Patrick-Anthony, is one of many tributes to her eldest son. Much of the wall space in the family’s house is dedicated to pictures of Patrick-Anthony and his father. “We like to play a game, find Patrick-Anthony,” Gina says. “But he’s in every room.”
‘We’re not afraid of HD’
Gina teaches the first grade; her class pet, Mr. Turtle, lives in a terrarium in their kitchen during school holidays. She’s also a licensed practical nurse who spends weekends working as a supervisor at a nursing home. Her son shares her work ethic: He waits tables and washes dishes at his aunt’s restaurant most weekdays.
Though he takes a certain pleasure in washing dishes — “he’s meticulous,” Gina says — Jonathan admits with a grin that his favorite part of the job is the free food. Especially the steak tip subs. And the pizza.
He has had some challenges from HD: He has fallen down the stairs a few times and experiences involuntary muscle movements, which can be severe during sleep. But he considers them minor inconveniences.
Jonathan and his younger sisters — Brianna, 15, and Natalia, 13 — regularly participate in awareness walks through the Huntington’s Disease Society of America (HDSA). And Jonathan is eager to raise funds, promote research and support other families living with HD.
Today, thanks to a growing pipeline of research programs and a wealth of internet resources, there’s a lot of help out there — and hope. “There’s no way to cure HD now, but maybe in the future,” Gina says.
A few years ago, Jonathan spoke at an event at Boston’s State House about living with HD. In sharing his experience, Jonathan’s primary goal is to make others with HD feel like they are not alone, and to ease their fears of what’s to come.
“We’re not afraid of HD,” says Gina, turning to Jonathan for confirmation.
He’s ready with a confident answer. “No.”