Transthyretin Cardiac Amyloidosis: Deadly 'Irreversible' Heart Condition Can Be Defeated, Study Shows

New findings by University College London (UCL) researchers show that a heart condition that was until now deemed irreversible could be effectively contained.

Heart Monitoring

The team in this new study found that symptoms of the condition were reversed in three men. Results from the research were published in The New England Journal of Medicine.

Prior to this study, most researchers had believed that this form of amyloidosis – transthyretin cardiac amyloidosis – was irreversible. Around 50 percent of patients die within four years of diagnosis.

“We have seen for the first time that the heart can get better with this disease,” said Professor Marianna Fontana, the study’s lead author. “That has not been known until now and it raises the bar for what might be possible with new treatments.”

Symptom reversal was not only based on reports by the subjects who recovered from the heart condition but was also confirmed with blood and imaging tests.

About the disorder

Transthyretin amyloidosis (ATTR) is a rare but severe heart condition. The progressive disorder is caused by an abnormal buildup of amyloid deposits. These deposits are made up of a blood protein known as transthyretin (TTR), which forms clumps or becomes misfolded. ATTR can either be hereditary/inherited or non-hereditary.

The accumulation of misfolded TTR proteins in the heart is more precisely referred to as ATTR amyloid cardiomyopathy (ATTR-CM). This condition has for many years been underdiagnosed. However, recent advances in imaging techniques have led to more diagnoses compared to two decades ago.

Improved imaging has not only resulted in higher diagnoses but has also enabled better monitoring of the condition’s state.

Treatments available for ATTR-CM at this time only aim at relieving its symptoms, such as fatigue and abdominal swelling. They do practically nothing to the amyloid protein buildup in the heart.

Reversing transthyretin cardiac amyloidosis

Following the report of improving symptoms by a 68-year-old patient, the UCL researchers proceeded to examine records of ATTR patients numbering 1,663. These helped them to identify two more people that also recovered from the condition.

Blood tests and multiple imaging techniques, including cardiovascular magnetic resonance (CMR) scans and scintigraphy (a nuclear medicine test), confirmed that the three men had indeed recovered. CMR scans showed that amyloid buildup cleared out almost completely.

Further investigations revealed an immune response that appeared to mainly target amyloid in the three men. The antibodies involved were found to be absent in other patients whose conditions did not improve. This may not prove that the antibodies were wholly responsible for the recoveries, however, as per the researchers.

“However, our data indicates that this is highly likely and there is potential for such antibodies to be recreated in a lab and used as a therapy,” said Professor Julian Gillmore, the study’s senior author. “We are currently investigating this further, although this research remains at a preliminary stage.”

If they can be harnessed, the observed antibodies could be combined with new therapies currently being worked on to effectively suppress the production of TTR proteins. One such therapy, NTLA-2001, is showing early promising results for halting disease progression.

References

Gillmore, J. D., Fontana, M., Gilbertson, J., Verona, G., Riefolo, M., Slamova, I., Leone, O., Rowczenio, D., Botcher, N., Ioannou, A. I., Patel, R. K., Razvi, Y., Martinez-Naharro, A., Whelan, C. J., Venneri, L., Duhlin, A., Canetti, D., Ellmerich, S., Moon, J. C., Kellman, P., Al-Shawi, R., McCoy, L., Simons, J. P., Hawkins, P. N. (2023). Antibody-Associated Reversal of ATTR Amyloidosis–Related Cardiomyopathy. New England Journal of Medicine. https://doi.org/10.1056/NEJMc2304584

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