‘Hopeless’ Huntington’s disease can be detected decades before it strikes, study says
Huntington’s disease is rare, only affecting about 30,000 people in the U.S., but its progression is painfully slow and combines debilitating symptoms from other diseases including ALS, Parkinson’s and Alzheimer’s.
Yet, there is currently no cure or treatment to slow or delay the disease’s development.
Now, new research revealed what could be the earliest sign of Huntington’s disease in the brain up to 24 years before symptoms such as impaired speech and limited movement appear.
The findings offer insight into what might be the critical window of treating the disease when a treatment becomes available, according to a study to be published in the June issue of The Lancet Neurology.
“Ultimately, our goal is to deliver the right drug at the right time to effectively treat this disease,” study lead author Dr. Sarah Tabrizi, a professor in the Huntington’s Disease Centre and Department of Neurodegenerative Disease at the University of College London (UCL), said in a news release.
“Ideally, we would like to delay or prevent neurodegeneration while function is still intact, giving gene carriers many more years of life without impairment,” she added.
People with Huntington’s disease (HD) carry a single mutation in their genes that was inherited from one or both parents, according to the Mayo Clinic. Symptoms often begin between age 30 and 40, with some rare cases appearing before age 20.
This mutation causes specific proteins called huntingtin to come together in toxic clumps in the brain that kill neurons necessary for normal brain function.
Luckily, there is a genetic test to check if someone has the mutation; all people need is one HD gene to have a 50% chance of developing the disease, which leads to death about 15 to 20 years after first symptoms appear, doctors say.
Symptoms include depression, irritability, muscle tremors and eventually the inability to speak and swallow. Other cognitive declines cause personality changes and dementia, according to the Mayo Clinic.
What did the study find?
The researchers recruited 64 individuals with this mutation and another 67 without it across the United Kingdom, with an average age of 29 years old.
The team then collected blood and spinal fluid samples from every participant, and conducted brain scans and cognitive tests, according to the study which received help from researchers at the University of Cambridge and University of Iowa.
The results showed that 47% of the mutation carriers had higher levels of a protein called neurofilament light (NfL) in their spinal fluid, which is often a sign of nerve cell damage: a common symptom in patients with HD.
What’s more, the mutation carriers were, on average, 24 years ahead of when HD typically develops, meaning scientists now have a better understanding of when the disease begins to appear— as silently as it does —in the brain.
The researchers did not find any “changes in thinking, behavior or involuntary movements commonly found in the disease, and there was very little evidence of brain scan changes,” the news release said.
It would be ideal to give future treatments to patients before symptoms such as muscle trembles and dementia take over, “but there may be a complex trade-off between the benefits of slowing the disease at that point and any negative effects of long-term treatment,” co-first author of the study Dr. Rachael Scahill said in the news release.
Clinical trial underway for potential treatment
The first human safety trial for a drug designed to slow and possibly stop the progression of HD began last year in January.
Only about 900 patients around the world were offered a spot in the highly desired trial, which is now in its final stage and is set to finish in September 2022.
But many were left to their own devices.
“We just wanted that opportunity to at least feel like we were fighting,” Heather Thurgood Wilmoth, whose husband was turned away from the trial because his body fat level was too high, told Stat in December 2019.
“The feeling like we’re able to fight, along with that hope— we felt like that was swept out from under us. And let’s face it: With Huntington’s, it’s a hopeless disease,” Wilmoth added.
However, the drug was found to lower the levels of the huntingtin protein responsible for cognitive decline in HD patients, which provides a glimmer of hope for the future of HD treatments.
