A Scanning Approach to Detect Transthyretin Amyloid Buildup in the Heart

Accumulation of transthyretin amyloid is one of the root causes of aging. This is a form of protein misfolding that products harmful deposits, amyloids, in tissues. In recent years this type of amyloid has been identified as the major cause of death in supercentenarians, but it was not until very recently understood to also be a significant cause of heart failure in the earlier stages of old age. Researchers here demonstrate a scanning methodology to detect transthyretin amyloid in heart tissue, which should hopefully lead to more resources directed towards finalizing the development of an existing therapeutic approach to breaking down and clearing this amyloid. That approach has been trialed successfully in a few patients, but is currently languishing in the endless regulatory pipeline somewhere prior to clinical availability. It is madness that so little funding and urgency is given to this sort of development, especially given the existence of an approach that appears to work: transthryretin amyloid clearance should be undertaken every few years by pretty much every adult over the age of 40, and the outcome would be significantly less heart disease.

A type of heart failure caused by a build-up of amyloid can be accurately diagnosed and prognosticated with an imaging technique, eliminating the need for a biopsy. The technique may also detect the condition - called transthyretin-related cardiac amyloidosis (ATTR-CA) - before it progresses to advanced heart failure. "This is a huge advance for patients with ATTR-CA, which is under recognized and often misdiagnosed. This test will spare certain patients from having to undergo a biopsy in order to get a definitive diagnosis. Many people with ATTR-CA are frail and elderly, so being able to avoid a biopsy, even when it can be done with a less-invasive catheter-based procedure, is a significant step forward."

ATTR-CA is one of many types of amyloidosis, a condition in which a protein breaks down and forms fibrils that deposit in organs and tissues, eventually causing the organs to fail. In ATTR-CA, the transthyretin protein breaks down and forms amyloid fibrils, which mainly accumulate in the heart, disrupting its function. Different types of amyloidosis require different treatments, so obtaining an accurate diagnosis is critical. ATTR-CA was once thought to be rare, but it's now known that ATTR-CA resulting from a normal variant of the transthyretin protein has a prevalence of about 32 percent in patients with heart failure over age 75 years at autopsy. The prevalence in hospitalized patients with heart failure is about 13 percent.

The diagnostic tool evaluated in the study is derived from bone scintigraphy, a form of single-photon emission computed tomography, or SPECT, that is conventionally used to detect bone cancer. In bone scintigraphy, patients are injected with a radioactive isotope with a particular affinity for bone that has remodeled due to bone cancer. Early on, researchers noticed that the isotope, technetium 99m pyrophosphate (Tc 99m PYP), also gravitates to amyloid deposits in the heart, a defining characteristic of ATTR-CA. In this study, the researchers examined the diagnostic accuracy of the Tc 99m PYP test for ATTR-CA in a retrospective study of 179 amyloidosis patients (121 with ATTR and 50 with other types). The researchers found that the imaging test was able to correctly identify ATTR in 91 percent of those diagnosed with the disease, and was able to rule out ATTR-CA in 92 percent of those with other forms of amyloidosis or no amyloidosis.

Link: http://newsroom.cumc.columbia.edu/blog/2016/08/24/amyloid-related-heart-failure-now-detectable-with-imaging-test/


Well this looks like a huge advance. What gets measured gets done, and humanity can now measure TTR amyloid build up. I think this should actually help the treatment get out of clinical development hell, as the test should create a huge market of people needing the treatment?

Posted by: Jim at August 25th, 2016 10:12 AM
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