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In the past, there were very few treatment options for transthyretin amyloidosis (ATTR amyloidosis). Today, several medications are available to help slow or even stop the disease from getting worse.
ATTR amyloidosis is a rare disease that occurs when a protein called transthyretin (TTR) changes shape. Misfolded TTR proteins then stick together and form harmful clumps called amyloid deposits. These deposits can build up in the nerves and other parts of the body, causing symptoms such as tingling, weakness, or pain in the hands and feet. When the nerves are mainly affected, the condition is called ATTR polyneuropathy (ATTR-PN).
However, it’s important to know that ATTR is a systemic disease — it can also affect the heart, kidneys, and eyes. There are two main types of ATTR:
Below is an overview of the main treatments for ATTR-PN, including how they work, how they’re given, and what makes each one different.
Patisiran (Onpattro) reduces the amount of TTR protein made by the liver. The drug uses a technology called RNA interference (RNAi), which “silences” the gene that makes the faulty protein.
This medication is given by IV infusion every three weeks at a clinic. Patisiran is approved for adults with hereditary ATTR polyneuropathy and has been shown to improve nerve function and walking ability. People who receive patisiran may also notice preserved heart and kidney health, since the treatment lowers TTR levels throughout the body.
Vutrisiran (Amvuttra) is a next-generation RNAi therapy, similar to patisiran but designed to be easier to take. It’s given as a small subcutaneous (under the skin) injection every three months. This medication is approved for hereditary ATTR polyneuropathy and ATTR cardiomyopathy.
Vutrisiran works by stopping the liver from making abnormal TTR, helping reduce amyloid deposits and nerve damage. In studies, vutrisiran improved nerve symptoms and helped people maintain strength and mobility over time.
Eplontersen (Wainua) uses a type of genetic technology called an antisense oligonucleotide. Like RNAi drugs, eplontersen helps the liver make less TTR protein, reducing the chance of amyloid deposits forming. It’s given once a month as a subcutaneous injection.
Clinical trials have shown that eplontersen improves nerve function and quality of life, with fewer side effects than older treatments. Eplontersen received U.S. Food and Drug Administration (FDA) approval for hereditary ATTR polyneuropathy in 2023 and is being studied for heart-related ATTR as well.
Before medications like those above became available, the main treatment for hereditary ATTR was liver transplantation. Because most TTR is made in the liver, replacing the liver with one that produces normal TTR can slow or stop disease progression.
However, this surgery carries major risks and requires lifelong medications to prevent rejection. Liver transplantation also isn’t helpful for wild-type ATTR, which doesn’t involve a genetic mutation (change). Thanks to newer drug options, liver transplantation is now no longer a first-line treatment. However, it may still be considered in select cases or in combination with other medications.
In addition to approved drugs, some treatments are used off-label to help reduce amyloid buildup or ease symptoms. Others may be available outside the U.S.
Tafamidis (Vyndaqel, Vyndamax) was one of the first medications designed specifically for ATTR amyloidosis. It helps stabilize the TTR protein, acting like a molecular glue to keep it in its normal shape so it doesn’t fall apart and form amyloid.
Tafamidis is taken once a day by mouth, making it convenient for many people. In the U.S., tafamidis is approved for both hereditary and wild-type ATTR cardiomyopathy (ATTR-CM). In some countries, it’s used for ATTR polyneuropathy — a use considered off-label in the U.S.
Research shows that tafamidis can slow nerve damage and improve quality of life when started early.
Inotersen (Tegsedi) was approved by the FDA in 2018. However, it was later discontinued in the U.S. due to low demand. It remains available in other countries. Inotersen is an antisense oligonucleotide that reduces the liver’s production of TTR protein, helping to prevent amyloid buildup.
This medication is self-injected once a week, usually in the thigh or abdomen. Because it may affect kidney function or lower blood platelet levels (important for blood clotting), people taking inotersen need regular blood tests to monitor for complications.
Studies show that inotersen helps maintain nerve health and supports daily functioning in people with hereditary ATTR polyneuropathy.
Doxycycline and tauroursodeoxycholic acid are sometimes used together to help break down amyloid and prevent new clumps from forming. These drugs aren’t officially approved for ATTR but have shown potential as a combination therapy in small studies. They’re rarely prescribed today because more effective medications are available.
Diflunisal, a nonsteroidal anti-inflammatory drug (NSAID), can help stabilize TTR in a way similar to tafamidis. Because diflunisal may cause stomach or kidney side effects, doctors typically reserve it for early-stage disease and use it with caution.
Most gene-targeting treatments — patisiran, vutrisiran, inotersen, and eplontersen — are approved only for hereditary ATTR polyneuropathy, since they’re designed to block the faulty gene that causes the problem.
For wild-type ATTR, which develops with age rather than genetics, stabilizers like tafamidis (and potentially acoramidis) are more commonly used. These treatments work directly on the TTR protein rather than the gene.
Although both types of ATTR involve amyloid deposits, their causes are different, so treatments need to target the right step in the process.
Researchers are studying combination therapies that use both a stabilizer and a gene-silencing drug to maximize benefits. There’s also growing focus on early diagnosis, since starting treatment before nerve damage becomes severe can lead to better outcomes.
New biomarkers and improved testing are helping doctors track how well treatments are working and catch changes sooner.
On MyAmyloidosisTeam, people share their experiences with amyloidosis, get advice, and find support from others who understand.
Are you looking to begin any of these promising treatments? Let others know in the comments below.
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