- Transthyretin cardiac amyloidopathy (ATTR-CM) is a rare but serious and progressive heart condition in which sticky, toxic proteins build up in the heart muscle and cause heart failure.
- Current treatments can relieve symptoms but cannot cure the disorder.
- Now, in an unprecedented discovery, scientists have reported that three patients have spontaneously recovered from the disease.
- They believe this discovery could lead to new treatments and perhaps even a cure.
Although rare, with approximately 5,000 to 7,000 cases Diagnosed in the United States every year, transthyretin cardiac amyloidopathy (ATTR-CM) is a devastating disease. Previously, symptoms were often thought to be due to aging, but improved imaging techniques have allowed diagnose the condition much simpler.
Transthyretin (TTR) is a highly conserved protein in the animal kingdom. TTR is made in the liver and transports the thyroid hormone thyroxine and retinol (vitamin A) throughout the body. However, mutations in this protein can cause it to form insoluble amyloid fibrils in heart muscle. These make the heart muscle stiff and rigid, leading to congestive heart failure.
In addition to heart failure, the condition, which is more common in men over 60, can cause irregular heartbeats (heart arrhythmias, atrial fibrillation) and other symptoms, such as carpal tunnel syndrome .
About half of people diagnosed with ATTR-CM die within four years of diagnosis. Early diagnosis and treatment can slow the progression of the disease, and people with the disease are treated to relieve symptoms of heart failure and arrhythmias and to slow the buildup of TTR.
However, so far no therapy has been found that can reverse the condition.
Now researchers led by scientists at University College London have, for the first time, reported spontaneous recovery from 3 patients with ATTR-CM. They think the recovery may be due to an immune response, suggesting that antibody treatments could be effective against the disease.
The conclusions are published in the New England Journal of Medicine.
“This communication in a New England newspaper represents the holy grail of amyloidosis treatment: proof of concept that a long-awaited cure for cardiac amyloidosis is not just speculation, but is achievable and possible. produced in nature.”
— Dr. Richard Wright, MDcardiologist at Providence Saint John’s Health Center in Santa Monica, California.
All three patients were unrelated elderly men. Patient 1 was 68 years old, patient 2 was 82 years old and patient 3 was 76 years old. They all presented class 2 heart failurewhich had been causing symptoms for more than six months.
Additionally, patients 1 and 2 had a history of bilateral carpal tunnel syndrome, patient 2 had atrial fibrillation, and patient 3 had recently been fitted with a pacemaker. After further investigations, all three were diagnosed with ATTR-CM.
They were followed at 1, 2 and 3 years. At follow-up, all three reported improvement in their symptoms, despite the absence of potentially disease-modifying treatments. Investigations – including blood tests, several imaging techniques including echocardiography (a type of ultrasound), cardiac magnetic resonance imaging (CMR) scans and scintigraphy (a nuclear medicine bone scan) – confirmed that amyloid was almost completely gone and heart function was back to almost normal.
“Cured is obviously a ‘big’ word, but the disease has reversed and they have few symptoms remaining.”
— Professor Julian Gillmorelead author, UCL Division of Medicine, director of the UCL Center for Amyloidosis
The researchers suggest that the improvement could be due to an immune response.
They found antibodies in all three men that specifically targeted amyloid deposits. These amyloid-targeting antibodies were not found in other patients who progressed normally.
A heart muscle biopsy from one of the patients showed an atypical inflammatory response surrounding the amyloid deposits. The researchers did not find this in biopsies from 286 patients with typical disease progression.
“Previous antibody treatment studies have confirmed that amyloid deposits can be cleared from abdominal viscera, but this is the first strong evidence that cardiac transthyretin deposits are likely to be cleared by exploiting the intrinsic manner of the body to get rid of unwanted invaders,” said Dr. Wright. Medical News Today.
The researchers suggest that if these antibodies can be exploited, they could be combined with new tested therapies that suppress TTR protein production. This would allow clinicians to remove amyloid and prevent further amyloid deposits.
Dr. Wright was excited about the potential of these findings:
“This is an amazing observation and one that should be reproducible with engineered antibodies or by ‘immunizing’ amyloidosis patients against their own amyloid protein.”
“Whether these antibodies caused the patients to recover has not been conclusively proven. However, our data indicate that this is very likely and that it is possible that such antibodies could be re-created in the laboratory and used as therapy.
— Professor Julian Gillmore
“As long as it can be undertaken safely, for example, without inducing serious heart inflammation, such treatment could remove all amyloid deposits and ‘cure’ amyloidosis, possibly for a long time. Given that amyloid takes years to settle, such an immune therapy might only need to be used once in a particular patient,” he added.
The UCL team is currently studying a therapy that could prevent the progression of this disease.
Professor Gillmore explained how the therapy works:
“This is a gene-editing therapy (the first of its kind) that knocks out the TTR gene, reduces the circulating concentration of TTR protein and thus slows down ongoing amyloid formation.”
Early results from their trial suggested it might be effective.
The findings of this study and early trial results may well lead to better treatments, giving hope to people with this progressive and deadly disease.
As Dr. Wright noted:
“The implications of this are vast and, if realized, could render all current amyloidosis therapies obsolete.”
