Hereditary transthyretin (hATTR) amyloidosis is a rare disease caused by mutations (changes) in the transthyretin (TTR) gene. These changes lead to proteins that don’t fold properly and stick together. The sticky proteins build up in organs and tissues throughout the body, which can cause serious health problems. hATTR amyloidosis tends to get worse over time, so most people need ongoing treatment to help manage it.

Since the late 2010s, doctors have developed new medications to treat hATTR amyloidosis. These treatments work in different ways — some prevent the body from making the harmful proteins, while others help the proteins keep their proper shape. Thanks to better tools and growing awareness, more people are getting diagnosed earlier. An early diagnosis can make treatments more effective.

Doctors and scientists now have a deeper understanding of the genetic mutations that cause this disease. This has led to the development of targeted therapies that often work better and have fewer side effects.

Research is ongoing. Scientists continue to discover new gene variants and treatment approaches that may lead to better outcomes. These advances are bringing new hope to people living with hATTR amyloidosis.

How hATTR Amyloidosis Affects the Body

In hATTR amyloidosis, your body makes a protein called transthyretin. When TTR proteins don’t fold correctly, they stick together and form clumps. These clumps can build up in organs, such as the heart, nerves, kidneys, and digestive system, causing damage over time.

Symptoms and disease progression can vary widely from person to person. Some people may experience polyneuropathy (nerve pain and numbness), others may develop serious heart problems like cardiomyopathy (a stiff or weakened heart muscle), and some have a combination of both. Because symptoms can be subtle or look like other conditions, diagnosis often takes years. That’s why awareness of hATTR amyloidosis is so important.

Today, more treatment options are available than ever before. Your doctor will suggest a treatment based on your specific symptoms and how far the disease has progressed. Often, a team of specialists — including a neurologist (a nerve specialist), cardiologist (a heart specialist), and geneticist — works together to manage care.

Researchers are still studying how well these treatments work over time. That’s why it’s important to stay in touch with your doctor and keep up with new research and clinical trials. Ongoing monitoring can help track whether your treatment is working and catch any new issues early. This personalized approach to care helps make sure your treatment continues to meet your changing health needs.

Treatments for hATTR Amyloidosis

For many years, the main treatment for hATTR amyloidosis was a liver transplant, because the liver produces the TTR protein. When TTR doesn’t fold correctly, it clumps together and can harm important organs.

These sticky proteins often affect the heart, nerves, and digestive system. People living with hATTR amyloidosis may experience:

• Heart problems — The heart may struggle to pump blood properly, causing symptoms like extreme fatigue and shortness of breath. This is often referred to as heart failure.
• Autonomic neuropathy — This type of nerve damage affects automatic body functions, such as blood pressure (which can cause dizziness) and digestion (which can lead to stomach problems).
• Peripheral neuropathy — This causes numbness, tingling, or pain in the hands, feet, or legs, which can make walking or doing daily tasks more difficult.
• Digestive symptoms — These may include stomach pain, nausea, loss of appetite, or diarrhea.

Treatments aim to manage symptoms and slow down disease progression. Some therapies stop your body from making abnormal TTR proteins, while others help keep the proteins from clumping. The overall goal is to protect your organs and improve quality of life by reducing pain and fatigue and helping you stay active and independent.

Although liver transplantation was once the main option, it comes with challenges, including limited availability, surgical risks, and the need for lifelong immunosuppression. These factors are important to consider when deciding whether to pursue a transplant or explore newer medical therapies.

So, what is the best treatment for hATTR amyloidosis? There’s no one-size-fits-all answer. Some people may benefit from a combination of therapies, or they may need to switch treatments over time based on how their condition responds. Each person’s treatment plan is personalized, depending on which organs are affected and how quickly the disease is progressing.

TTR Stabilizers and Their Long-Term Use

In hATTR amyloidosis, the TTR protein doesn’t fold properly. When this happens, the misfolded proteins clump together and build up in the body, damaging organs. Doctors may prescribe TTR stabilizers, a group of medications that help keep these proteins in the correct shape.

Tafamidis and Tafamidis Meglumine

Tafamidis (Vyndamax) and tafamidis meglumine (Vyndaqel) are approved by the U.S. Food and Drug Administration (FDA) for transthyretin amyloid cardiomyopathy, including both hATTR and wild-type forms. These stabilizers prevent TTR proteins from clumping, which helps slow disease progression — especially when treatment begins early.

Long-term studies show that tafamidis can improve heart function and help people live longer. Tafamidis is taken by mouth, once daily. Many people taking tafamidis long-term report improved stamina, including better ability to walk, exercise, and manage daily tasks.

Acoramidis

Another stabilizer, acoramidis (Attruby), was approved in 2023 to treat ATTR cardiomyopathy. Studies show it can improve heart function and how people feel day to day. It is also taken once daily by mouth, offering a convenient option for long-term treatment. Because it’s newer, researchers are still tracking how well it works and how safe it remains over time.

Off-Label Treatments

Diflunisal is sometimes prescribed off-label, meaning it’s not specifically approved for hATTR but may still be used when doctors believe it could help. It’s a nonsteroidal anti-inflammatory drug (NSAID) that also has TTR-stabilizing effects.

Because diflunisal can affect the stomach and kidneys, it requires close monitoring. People who take this medication usually need regular checkups and lab tests to make sure it’s safe for them to continue.

Gene Silencers and How They Work Over Time

Gene-silencing therapies target the underlying cause of hATTR amyloidosis by stopping the body from making abnormal TTR protein. These medications work by blocking the genetic instructions (messenger RNA) that tell cells to make TTR. They use two main approaches: RNA interference (RNAi) and antisense oligonucleotides (ASOs).

These treatments go after the root of the disease and are showing strong results, especially when started early.

Following are FDA-approved gene-silencing drugs for hATTR.

Patisiran

Patisiran (Onpattro) was the first gene-silencer approved for hATTR amyloidosis. It uses a lipid nanoparticle delivery system to transport RNA interference molecules into cells. Patisiran is given through an IV and is designed to slow nerve damage.

Because it’s delivered through an IV, there’s a risk of infusion-related side effects, so people are monitored during and after treatment. In long-term studies, patisiran has been shown to improve nerve function and slow disease progression.

Inotersen

Inotersen (Tegsedi) is an ASO therapy that also works to slow nerve damage. It’s given as a once-weekly subcutaneous (under the skin) injection and is often used by people who have primarily nerve-related symptoms.

Regular blood tests are required to monitor platelet levels, as inotersen can affect blood clotting.

Vutrisiran

In 2025, the FDA approved vutrisiran (Amvuttra) for people with ATTR cardiomyopathy, in addition to its previous use for polyneuropathy. It’s an RNAi therapy that’s injected once every three months in a hospital or clinic.

Vutrisiran has been shown to improve heart function, reduce shortness of breath, and enhance quality of life in clinical trials. Its less frequent dosing schedule may be convenient for people needing long-term care.

Eplontersen

Another new gene-silencing treatment, eplontersen (Wainua), was approved in 2024 for treating nerve symptoms caused by hATTR amyloidosis. It’s given as a monthly injection people can give themselves. Early studies show that eplontersen improves nerve-related symptoms and slows disease progression.

Researchers are studying whether it may also help with heart symptoms in the future.

Long-Term Benefits and Flexibility

Gene-silencing therapies not only help slow the disease, but also provide ongoing benefits when used over time. These treatments offer more flexibility — some can be taken less often or even at home — making them a good option for people who want to manage their condition without frequent clinic visits.

As new data becomes available, researchers are working to reduce side effects and improve effectiveness. This allows doctors to better tailor treatment plans to each person’s health needs and lifestyle.

Weighing the Risks and Benefits of Treatment

Every treatment comes with potential side effects. Your doctor will work with you to find the option that fits best based on your age, overall health, symptoms, and personal preferences.

It’s important to talk openly with your doctor about what matters most to you, whether that’s reducing pain, preserving mobility, or minimizing side effects. Together, you can make a decision that supports your goals and values.

Ongoing follow-up visits are key. These check-ins allow your care team to monitor how well the treatment is working, make any necessary changes, and watch for new or changing symptoms.

Your treatment plan may also include physical therapy, nutrition support, and other services to help you stay strong, manage symptoms, and improve daily life.

Talk With Others Who Understand

MyAmyloidosisTeam is the social network for people with amyloidosis and their loved ones. Members come together to ask questions, give advice, and share their experiences with others who understand life with amyloidosis.

How did you make choices about your hATTR amyloidosis treatment? Share your experience in the comments below, or start a conversation by posting on your Activities page.