Several therapies exist to suppress transthyretin (TTR) levels in patients with transthyretin amyloidosis, including those with transthyretin amyloid cardiomyopathy (ATTR-CM). However, the potential risks of long-term treatment remain uncertain, according to a review published in the Annals of Medicine.
“We must delve deeper into the physiologic functions of TTR and the consequences of prolonged alteration of TTR levels on patient outcomes,” the researchers wrote.
What is transthyretin?
Transthyretin (TTR) is a transport protein produced in the liver. Its role is to carry vitamin A (retinol) and thyroxine, a thyroid hormone, around the body. In ATTR-CM, it is faulty or unstable, causing it to misfold and become deposited in the heart, nerves and other internal organs.
Previous studies have established that TTR plays critical roles in several biological processes, including nervous system protection, cognitive function, fetal development, muscle regeneration and many more. In fact, high levels of TTR may lower the risk of a variety of diseases such as diabetes, dementia and osteoporosis.
Read more about ATTR-CM treatment and care
Many of the therapies aimed at treating ATTR focus on decreasing levels of misfolded TTR in the body, the cause of the disease. These include drugs that silence the TTR gene, those that clear out the buildup of amyloid fibrils and, more recently, gene editing therapies that inactivate the TTR gene.
Many of the existing treatments have been shown to significantly improve outcomes in patients with ATTR in clinical trials. Because of the diverse roles TTR plays throughout the body, though, more work needs to be done to understand how these therapies may impact patient health over the long term, the authors argue.
The researchers suggest that patients receiving TTR knockdown therapies should have periodic cognitive tests. Additionally, future studies should be conducted to monitor patients over time for changes in metabolism, along with bone and muscle health.
“Critical questions, such as whether chronically low TTR levels predispose patients with ATTR to other serious and fatal medical conditions, must be explored,” they concluded. “It is imperative to investigate the relationship between the duration and degree of TTR suppression and the associated risks of serious disease.”
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