OHSU Tests CRISPR Gene Editing for Transthyretin Amyloidosis in Clinical Trial
Key Insights
Oregon Health & Science University (OHSU) is conducting a clinical trial using CRISPR gene-editing technology to treat transthyretin amyloidosis (search), a life-threatening heart condition.
The trial, named MAGNITUDE, aims to block the production of a protein that causes the disease, offering a potential one-time therapy.
The study treatment, NTLA-2001, involves molecules that enter the liver to halt the production of transthyretin (search) proteins damaging the heart.
A retired teacher from Grants Pass, Oregon, is the first person in the state to participate in a clinical trial testing gene-editing technology for a heart condition. The trial, led by Oregon Health & Science University (OHSU), is evaluating a technique that blocks the production of a protein responsible for transthyretin amyloidosis (search), a life-threatening condition.
On October 31, Ken Hawkins, 77, traveled to OHSU to participate in the trial. According to Ahmad Masri, M.D., principal investigator for the trial at OHSU, transthyretin amyloidosis (search) was once thought to be rare, but is now being diagnosed more commonly as people live longer and imaging technology improves. He added that he is optimistic that this leading-edge study treatment holds promise as a one-time therapy, potentially reducing a significant health care burden and transforming care for this life-threatening disease.
Understanding Transthyretin Amyloidosis
Transthyretin (search) is a protein mainly produced in the liver that transports thyroid hormone and vitamin A in the body. In transthyretin amyloidosis (search), the protein becomes structurally unstable and clumps together within cells of tissues and organs. This condition can lead to nerve pain, gastrointestinal issues, and, in severe cases, heart failure. While it is most common in older adults, a gene mutation can cause the protein to become unstable even in younger people.
The Clinical Trial: MAGNITUDE
Hawkins is participating in the MAGNITUDE trial, a Phase 3 randomized controlled study. The study treatment, known as NTLA-2001, involves molecules that enter the liver and form microscopic CRISPR-Cas9 enzymes. These enzymes are designed to seek out and halt the production of transthyretin (search) proteins that damage the heart. OHSU is one of 22 sites nationwide administering the clinical trial, and the only site in Oregon. The trial is ultimately intended to enroll 765 patients.
OHSU's Expertise in Gene Therapy
OHSU has been actively advancing scientific understanding of gene therapy techniques. In 2017, a study published in Nature demonstrated a method for repairing genes in human embryos to correct a gene mutation that causes hypertrophic cardiomyopathy (search). Unlike that study, which aimed to prevent disease development in the future, the current clinical trial tests a therapy designed to help people today.
Masri noted that while not everyone experiences significant symptoms of amyloidosis, the condition affects an estimated 5% to 10% of people who are 75 years old, causing severe effects in approximately 100,000 people in the U.S.