Unexpected patient recoveries from an untreatable heart condition have pointed to potential therapies, British doctors reported last night.
A team at UCL and the Royal Free Hospital, London, UK, have described the cases after their transthyretin cardiac amyloidosis, which is usually irreversible, spontaneously reversed.
The improvements of the patients, aged 68, 76 and 82, were confirmed by objective assessments including cardiovascular magnetic resonance (CMR) scans, which showed the build-up of amyloid proteins in the heart had cleared.
The findings were reported in the New England Journal of Medicine last night.
Lead author Professor Marianna Fontana, of UCL Division of Medicine, said: “We have seen for the first time that the heart can get better with this disease. That has not been known until now and it raises the bar for what might be possible with new treatments.”
The researchers found evidence of an immune response in the three men that specifically targeted amyloid, which were not found in other patients whose condition progressed as normal.
Senior author Professor Julian Gillmore, head of the UCL Centre for Amyloidosis at the Royal Free Hospital, said although there is conclusive evidence that the antibodies caused the patients’ recovery, its data indicates it is highly likely.
“There is potential for such antibodies to be recreated in a lab and used as a therapy. We are currently investigating this further, although this research remains at a preliminary stage,” he added.
Transthyretin (ATTR) amyloidosis is caused by amyloid deposits composed of transthyretin (TTR) and can be hereditary or non-hereditary.
Current treatments on the NHS aim to relieve the symptoms of heart failure, but do not tackle the amyloid. Advances in imaging techniques has meant more people being diagnosed with the disease than 20 years ago, which enables them to be monitored more closely.
The latest study, supported by the Royal Free Charity, began when a 68-year-old patient reported that his symptoms had improved.
This prompted the research team to look through records of 1,663 patients diagnosed with ATTR-CM and two more patients where patients reported improved symptoms were identified.
All three men had blood tests, several imaging techniques including echocardiography, CMR scans and scintigraphy, while one also had an assessment of exercise capacity.
CMR scans showed heart structure and function had returned to a near-normal state and amyloid had almost completely cleared.
One of the patients underwent a heart muscle biopsy, which showed an atypical inflammatory response surrounding the amyloid deposits, including macrophages, suggesting an immune reaction.
The research team also found in the three patients antibodies that bound specifically to ATTR amyloid deposits in mouse and human tissue and to synthetic ATTR amyloid.
They hope if these antibodies can be harnessed, they could be combined with new therapies that are being trialled that suppress TTR protein production, which could result in the clearing of amyloid and prevention of further amyloid deposition.
One promising therapy is a single intravenous infusion of NTLA-2001, a novel gene-editing therapy based on CRISPR/Cas9, which early trial results indicate may stop disease progression.
Fontana M et al. Antibody associated reversal of ATTR amyloidosis cardiomyopathy. NEJM 7 June 2023.
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