Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare type of heart disease. It makes it hard for your heart to pump as much blood as your body needs. It can also affect your nerves and other organs. But in recent years, ATTR-CM research has made huge advances. Doctors now have better ways to manage your symptoms and improve your quality of life.
Here’s a look at the latest findings and new research that has doctors feeling hopeful.
TTR Stabilizers
ATTR-CM happens when a protein in your body called transthyretin (TTR) starts to fold in on itself. These clumps gather in your heart. When they make their way into your bloodstream, they also end up in other parts of your body.
There isn’t a way to break up these harmful protein deposits. But researchers have developed medications known as TTR stabilizers, which can prevent more TTR clumps from forming.
They include acoramidis (Attruby) and tafamidis (Vyndaqel), “[which] prevent protein misfolding and have shown impressive outcomes in clinical trials,” says Kevin Shah, MD, a cardiologist at MemorialCare Heart & Vascular Institute at Long Beach Medical Center in Long Beach, CA.
Researchers haven’t stopped there. They keep trying to better understand TTR. For instance, learning more about its complex, tangled structure could help drugmakers figure out new ways to target it.
Gene-Silencing Therapies
ATTR-CM is caused by a mutation (change) in a gene. Sometimes, it’s passed down through your family, but it can also happen for unknown reasons. A new class of drugs called gene silencers bind to TTR’s messenger RNA (mRNA), which is like its instruction manual, and damages it. This makes your body produce less TTR protein.
Vutrisiran (Amvuttra) is the first gene silencer approved by the FDA to treat ATTR-CM. In a clinical trial, 655 adults with ATTR-CM were followed for about three years. Some were given a placebo while others took vutrisiran. The participants treated with vutrisiran had fewer heart-related trips to the hospital and fewer deaths.
Other gene silencers that show promise in treating ATTR-CM include inotersen and patisiran.
Both TTR stabilizers and gene-silencing therapies “have demonstrated improvements in quality of life for patients,” Shah says. “Having multiple therapeutic options with different mechanisms allows for more personalized treatment strategies.”
Amyloid-Depleting Antibodies
These medications, which are still in clinical trials, approach ATTR-CM in a different way.
“[Amyloid antibodies] can target existing protein deposits and reverse some of the disease manifestation that already exists, as opposed to slowing down disease process,” says Mary Greene, MD, a cardiologist at Manhattan Cardiology in New York City.
For instance, an antibody called coramitug appears to be able to bind to TTR and “eat away” at clumps of amyloid. An early clinical study found that it was well tolerated in participants.
Another amyloid depleter, ALXN2220, is being tested against a placebo in a phase III clinical trial of people with ATTR-CM. Researchers developed the drug by studying the memory B cells in healthy older people. Memory B cells are specialized white cells that remember certain threats to your body so they can be found and attacked quickly by your immune system.
Gene Editing
Powerful technology, like CRISPR, is now able to make small, specific changes to genes. Among the ATTR-CM therapies being tested is NTLA-2001, a gene-editing agent that helps decrease the amount of TTR in your blood serum.
Some data suggests that gene editing therapy could do more than help manage your heart symptoms and extend your quality of life. It could be an effective one-time treatment for ATTR-CM.
Finding ATTR-CM Sooner
On average, it can take six years to be diagnosed with ATTR-CM. Experts are working to help doctors get better at spotting some of the early warning signs, including:
- Carpal tunnel syndrome in both hands
- Numbness, tingling, or pain in the hands or feet
- Spinal stenosis (narrowing of your spine)
- Ruptured biceps (upper arm) tendon
And when tests are ordered to get more information, “there’s better non-invasive imaging nowadays,” Greene says. “Bone scintigraphy [scan], cardiac MRI, and PET CT allow for earlier and more accurate diagnosis, which has led to less of a need for invasive biopsies to confirm the diagnosis.”
AI is starting to assist doctors in reading scan results, but it’s in its early stages.
Future Challenges — and How You Can Help Face Them
“The newer agents available for ATTR-CM are some of the mostly costly medications on the market, so this remains a great challenge for many patients,” Shah says. “The other primary challenge is we don't have great data on when to use which agent, like stabilizers and silencers, and in what order they should be combined.”
That leaves doctors to use their best judgment when choosing a treatment to use. In the future, you may end up being prescribed more than one of these medications.
“Ultimately, I think the ability to combine approaches will be beneficial to patients, but there are no specific guidelines as of yet,” Greene says.
One way that you can help with ATTR-CM advances, and perhaps benefit your own health, is by joining a clinical trial. These studies rely on volunteers to try out new ATTR-CM treatments.
“Clinical trials can be considered at various disease stages,” Shah says. “If you’re not improving on current treatment or are willing to participate in a treatment which is still in the investigational phase, ask your medical team about your options for clinical trials.”
