A retired teacher from Grants Pass is the first person in Oregon to participate in a new clinical trial testing the promise of gene-editing technology on a heart condition.
On Oct. 31, Ken Hawkins, a 77-year-old retiree from Southern Oregon, traveled to Oregon Health & Science University to participate in a clinical trial testing a technique that blocks the production of a protein that causes a life-threatening condition known as transthyretin amyloidosis.
"This condition was once thought to be rare, simply because it was missed. But we're seeing it more commonly as people live longer and as imaging technology has improved," said Ahmad Masri, M.D., principal investigator for the trial at OHSU and an associate professor of medicine (cardiovascular medicine) in the OHSU School of Medicine. "We're optimistic that this leading-edge treatment holds promise as a one-time therapy, thus reducing a significant health care burden and saving lives."
Transthyretin is a type of protein mainly produced in the liver that transports thyroid hormone and vitamin A in the body — normally a good thing.
In transthyretin amyloidosis, the transthyretin protein becomes structurally unstable such that it no longer functions normally and begins to clump together within cells of tissues and organs in the body.
Although this is most common in older adults, in some cases a gene mutation codes a misshapen protein prone to instability even in younger people. The condition, known as amyloidosis, can lead to nerve pain, gastrointestinal issues and, in severe cases, heart failure.
Even though Hawkins is taking another medication meant to stabilize the condition, he knows the protein has dangerously built up in his heart.
Because it's a randomized controlled trial, there is a chance that Hawkins received only an inert placebo. But he's hoping he gets the good stuff: the microscopic machinery to make billions of microscopic CRISPR-Cas9 proteins able to halt production of heart-damaging transthyretin protein in the liver.
Either way, he's willing to contribute to a clinical trial that he believes will make a difference in the lives of countless others.
"Here, I have a chance," he said. "Plus, somebody has to do these tests for them to know whether or not it really works. I'm willing to contribute to finding the answer."
Maintaining an active lifestyle
Hawkins had always relished an active lifestyle.
As a retired teacher and coach, he enjoyed outings with his wife, golfing with his friends and working in the yard of his home in Grants Pass. In recent years, he noticed he would tire out more easily — but he figured it was a normal sign of aging.
Then came the shortness of breath.
After a referral to a cardiologist in nearby Medford a year ago, he was diagnosed with transthyretin amyloidosis and recommended as a possible candidate for a clinical trial just getting underway at OHSU. He soon made the four-hour drive north to Portland, where Masri and clinical trial coordinators in the OHSU Knight Cardiovascular Institute conducted a series of tests over several subsequent visits to ensure he would be an ideal candidate.
"I can't tell you how happy I've been with how I've been treated up there," he said. "It's been amazing."
Hawkins is the first to be enrolled in the clinical trial, but he won't be the last. OHSU has one of the largest centers in the Pacific Northwest, treating about 350 patients with amyloidosis along with hundreds of other patients involved in clinical trials to treat other types of heart conditions. It draws patients from across the state, as well as California, Idaho, Montana and Alaska.
"We're excited to be one of the few centers offering access to this clinical trial on the West Coast," Masri said.
OHSU has an advanced multidisciplinary cardiomyopathy program. While this clinical trial is the first gene therapy applied to a disease that directly affects the heart muscle, OHSU is at the forefront of other therapies advancing toward clinical testing in people.
OHSU advances gene therapy techniques
OHSU has been active in advancing scientific understanding of gene therapy techniques, including a groundbreaking study published in 2017 that used CRISPR in early human embryos to correct a gene mutation that causes hypertrophic cardiomyopathy. In that case, the gene repair would prevent a disease from developing in the future.
In contrast, the new clinical trial tests a therapy designed to help people today.
"Not everyone experiences significant symptoms of amyloidosis, but we believe the condition affects 5% to 10% of people who are 75 years old," Masri said.
He said the condition causes severe effects in an estimated 100,000 people in the U.S.
OHSU is one of 22 sites nationwide administering the clinical trial known as MAGNITUDE, and the only site in Oregon. Following pilot study results published in 2021, Intellia Therapeutics Inc., announced in March that the first participant had enrolled in the phase 3 randomized controlled trial that's ultimately intended to enroll 765 patients.
The study treatment is known as NTLA-2001.
