Deadly Heart Condition Reversed in Three Men

Three men are now free of a heart muscle disease that can that was previously thought to be irreversible.

Transthyretin cardiac amyloidosis (ATTR-CM) is a life-threatening disease of the heart muscle that occurs when deposits of a misshapen protein called transthyretin (TTR) build up in the heart and stiffen the walls of the ventricle, making it unable to relax and fill with blood properly. ATTR-CM is a progressive disease that may ultimately lead to heart failure.

While the condition was previously thought to be irreversible, a new study, published as a letter in The New England Journal of Medicine, describes cases of three men aged 68, 76, and 82 who recovered from ATTR-CM.

The study started with a 68-year-old patient reporting his symptoms improving. This prompted the researchers to look through records of 1,663 patients diagnosed with the condition. Of those, two more recovering patients were identified.

CMR scans of the patients showed heart structure and function had returned to a near-normal state, and deposits (amyloid) of misshapen transthyretin completely cleared.

A heart muscle biopsy in one of the three patients revealed an atypical inflammatory response surrounding the amyloids, suggesting an immune reaction. No such inflammatory response was detected in 286 biopsies from patients with a typical clinical course.

The researchers found antibodies in the three patients that bound specifically to ATTR amyloid deposits in mouse and human tissue and synthetic ATTR amyloid. No such antibodies were present in 350 other patients in the cohort with a normal progression of the disease.

If these antibodies could be harnessed, they could be combined with new therapies being trialed that suppress TTR protein production. This would enable clinicians to clear away amyloid as well as prevent further amyloid deposition.

One such therapy is a single intravenous infusion of NTLA-2001, a novel gene-editing therapy based on CRISPR/Cas9. In a recent trial involving six patients with hereditary ATTR-CM, reduction in serum TTR protein concentration ranged from 52% to 87%, depending on the dose, during the first 28 days.

Currently, there is no cure for ATTR-CM or a drug that would reduce or clear existing amyloid deposits. However, medications can slow or stop the buildup of protein deposits.

There are two types of transthyretin cardiac amyloidosis:

• In hereditary ATTR-CM, there’s a variant in the TTR gene, which results in amyloid deposits in the heart, nerves, and other organs. Although symptoms of this type of ATTR-CM may start as early as 20 years old, being 50 and older is considered a risk factor. The disease primarily affects males and African Americans.
• Wild-type ATTR-CM does not involve a variant in the transthyretin gene. It most commonly affects the heart and starts after the age of 65.

Jon Spiers, chief executive of the Royal Free Charity, says: "This work not only represents a major breakthrough in our understanding of cardiac amyloidosis but crucially opens up new possibilities for more effective treatment options."