Understanding ATTR: The Challenges of Amyloidosis

Transthyretin amyloidosis (ATTR) is a complex medical condition that happens when a protein called transthyretin (TTR) does something different than what it’s supposed to do in the body. Normally, TTR is a four-piece protein produced mostly in the liver that helps carry important substances, like thyroxine (thyroid hormones) and vitamin A, throughout the body.  When someone has ATTR, the pieces of TTR fall apart, misfold, and change shape. These pieces bind together to form larger structures called amyloid fibrils, which do not break down normally. These amyloids can then build up in different parts of the body, including nerves, the heart and other organs. When this happens, it can cause problems because the amyloids interfere with the normal functioning of those body parts.  

ATTR can be divided into two types: hereditary or wild-type.  

Understanding The Differences Between Hereditary and Wild-Type ATTR

Hereditary ATTR (hATTR) Wild-Type ATTR (ATTRwt)
  • This type of ATTR is caused by a genetic mutation, meaning there is a gene that your family may be passing down from generation to generation
  • Age of onset is typically 30-50 years of age and older
  • While hATTR can affect and damage multiple organs and tissues, hATTR may predominantly affect the nerves (hATTR-PN), leading to symptoms like numbness, muscle weakness and problems with balance; or it can predominantly affect the heart (hATTR-CM)
  • A genetic test can help you determine if you carry the gene that causes hATTR
  • Nerve conduction studies and biopsies of affected tissues may be used to confirm the presence of amyloid deposits
  • ATTRwt is not linked to genetics. The exact cause of ATTRwt is not fully understood, but it is believed to be associated with the aging process and gradual misfolding of TTR
  • ATTRwt is more common in older adults. People with ATTRwt are usually 60 years of age or older and more commonly male
  • This type of ATTR mainly affects the heart (ATTRwt-CM), which can cause symptoms of shortness of breath but can also cause carpal tunnel syndrome, spinal issues, and may sometimes affect the nerves
  • Diagnosing ATTRwt may involve a combination of various tests (like heart ultrasounds, magnetic resonance imaging (MRI), computed tomography (CT) scans, and biopsies)

Living With ATTR

ATTR is a complex disease, and a lack of access to information about it can often leave patients in the dark.

“ATTR isn’t something a lot of people are talking about, which makes it harder for doctors to diagnose and for patients to understand. We need people to recognize that this condition exists, and we need more information out there for doctors and patients. Right now, patients need to be their own advocates because their lives are at stake. With more information and awareness, diagnosis could happen faster, and patients would feel more supported and seen,” said Mike, an ATTR patient.

To help provide people who have been diagnosed with ATTR and their loved ones with more information, AstraZeneca has launched www.MyATTRroadmap.com. This website was developed to provide resources and information for people living with ATTR so you can better understand your condition and find support from the amyloidosis community. After what was likely a long road to diagnosis, it’s important to have the information you need to continue on your ATTR journey.

To help increase awareness of ATTR among the healthcare community, AstraZeneca has launched a comprehensive disease education site for healthcare practitioners (www.seethepattrns.com) about the symptom patterns associated with ATTR to facilitate diagnosis. Our hope is that by increasing awareness and knowledge of these disorders, we can help empower health care providers to quickly and accurately diagnose ATTR to ensure patients are appropriately treated in a timely manner.

Why Is ATTR a Challenge to Diagnose?

The journey to an ATTR diagnosis has its challenges. People with ATTR often see multiple specialists before receiving an accurate diagnosis, and this can take an average of more than three years. There are many reasons why ATTR can be challenging to diagnose, including:

  1. Symptoms are similar to other more common medical conditions: Both hereditary ATTR and wild-type ATTR can cause symptoms like neuropathy (numbness, tingling, weakness), heart issues (heart failure, irregular heart rhythms), and gastrointestinal problems. These symptoms can be mistakenly attributed to other conditions, delaying an accurate diagnosis.
  2. Lack of disease awareness: Many patients and even some healthcare providers may not often encounter ATTR, as it is a relatively rare disease, and therefore have a lack of awareness and experience diagnosing the condition. A lack of awareness can lead to misdiagnosis or a delay in seeking appropriate evaluation.
  3. Specialized Tests: Specialized tests, such as genetic testing, nerve conduction studies, and/or advanced heart imaging, are needed for a definitive diagnosis. These tests may not be routinely ordered unless there is a strong suspicion of amyloidosis.

Due to these challenges, diagnosing ATTR often requires involving experts in various medical fields, including cardiology, neurology and gastroenterology. Early and accurate diagnosis is critical for appropriate management and treatment.

AstraZeneca in CVRM and ATTR
AstraZeneca is committed to making medicines available for the millions of people worldwide living with Cardiovascular, Renal and Metabolic (CVRM) diseases. We are committed to transforming amyloidosis treatment, helping patients with underdiagnosed diseases, such as ATTR and other amyloidosis conditions. Through advancing the science and understanding of these diseases, we aim to give patients more time and ability to do what matters most to them, offering hope of living longer with a higher quality of life.