Wild-type ATTR Amyloidosis (ATTRwt) is age related and mainly affects the heart.
Transthyretin (TTR) is a natural protein mostly made in the liver. Its role is to transport a hormone and vitamin A (thyroxine and retinol) around the body, which is why it’s called transthyretin. In ATTR amyloidosis, this protein becomes unstable. When that happens, it folds the wrong way, attaches to, and builds up in different organs and tissues as amyloid.
This can lead to a type of heart disease called cardiomyopathy. ATTRwt is most often found in men over 60. We believe that wild-type amyloidosis is massively under-diagnosed and is often the underlying cause of heart failure.
Watch this 3D animated overview of ATTR amyloidosis:
You can download and print our Wild-Type ATTR Overview packet by clicking here.
In this video, Omar Siddiqi, MD from the Boston University Amyloidosis Center explains what Wild-Type ATTR (ATTRwt) amyloidosis is and how it affects the body.
You can download the slides from Dr. Siddiqi’s video above by clicking here.
Diagnosis, Symptoms, and Treatment
If ATTR amyloidosis is suspected, a number of tests are carried out including an abdominal fat pad biopsy to confirm the presence of amyloid deposits.
Tests are also done to determine the effect of the amyloid deposits on the heart, nerves and other organs. These tests include blood, nerve and muscle tests, echocardiogram, MRI and other types of scans. In some cases, organ biopsies may also be completed to determine organ involvement. Some scans can help identify the type of amyloidosis and distinguish ATTR from AL amyloidosis in the heart. Doctors also use other tests, called immunohistochemistry and mass spectrometry, to differentiate between ATTR and AL amyloidosis.
To distinguish between wild-type and hereditary ATTR amyloidosis, a blood test to screen for genetic mutations causing hATTR is necessary. The absence of these genetic mutations will confirm a diagnosis of wild-type ATTR amyloidosis.
Symptoms usually start after the age of 60 and are mostly associated with cardiomyopathy. Amyloid deposits in the heart make the heart wall stiffen and work inefficiently. Eventually this leads to congestive heart failure with symptoms such as shortness of breath, leg swelling, fatigue, nausea and an irregular heartbeat or palpitations.
Recent studies have shown that other symptoms unrelated to the heart may also exist and in some cases often are present 8-10 years before heart-related symptoms, the most commonly reported is carpal tunnel syndrome.
In ATTR amyloidosis there are several different therapeutic approaches, which aim to do one of the following:
- Stabilizing the TTR protein
- Stopping the production of TTR protein
- Removing the amyloid deposits
Stabilizing the TTR protein: The approach of TTR stabilizers is to stop the TTR protein from forming amyloid deposits. There are several drugs which aim to treat ATTR in this manner:
- Vyndamax (tafamidis) – Approved on May 3, 2019 for the treatment of transthyretin amyloidosis cardiomyopathy (ATTR-CM) – view factsheet
- Attruby (acoramidis) – Approved by the FDA for use in the U.S., Attruby is a TTR stabilizer developed for treating patients with transthyretin amyloidosis (ATTR) who have heart involvement (cardiomyopathy) – view factsheet
- Diflunisal – Approved in the U.S. by the FDA as a non-steroidal, anti-inflammatory drug (NSAID) that has shown to bind to the TTR protein in the blood and may thereby prevent the formation of amyloid.
Stopping the production of TTR protein: The approach in stopping production of TTR proteins is through ‘gene silencing.’ Novel treatments known as “gene silencers” have shown promising results in clinical studies. They prevent TTR protein production by blocking the TTR gene. The gene silencing drug Vutrisiran (Amvuttra) has been approved for use for ATTR cardiomyopathy and ATTR polyneuropathy.
Drug factsheet:
- Vutrisiran (Amvuttra) — view factsheet
Removing amyloid deposits: The approach in removing amyloid deposits aims to make amyloid fibrils easier for the body to identify and remove from organs. There are currently no approved drugs aimed at removing amyloid deposits in wild-type ATTR.
Drug status report:
- Coramitug (PRX004) – Currently being tested in clinical trials.
Supportive treatment: Although they do not address the underlying cause, supportive treatments are important to help alleviate symptoms and improve quality of life. Overall, factors such as age, general health and extent of organ damage are taken into account when deciding on treatment.
In this video, Omar Siddiqi, MD from the Boston University Amyloidosis Center gives an overview of Wild-Type ATTR (ATTRwt) amyloidosis treatments.
You can download the slides from Dr. Siddiqi’s video above by clicking here.
My Amyloidosis Pathfinder
Find, compare, and contact the treatment centers that fit your personal needs with ARC’s online My Amyloidosis Pathfinder (MAP) tool. Your personalized MAP profile will connect you to the centers and clinical trials that match what you’re looking for.
Additional Support
Finding the right support is important to help you manage your care. Talking to people who listen and answer your questions is a key part of feeling well. At ARC, we’re here to provide resources and information to guide you on your journey—you don’t have to face this alone. There are also many support groups around the world where you can connect with others who understand. Find a support group and find out more about our PEER Link program.
