In an exceptional medical event, three senior men with a formerly irreversible cardiac disease known as transthyretin cardiac amyloidosis, made a spontaneous recovery. Their remarkable turnaround, confirmed via medical imaging, has led the research team at University College London (UCL) and the Royal Free Hospital to discover an amyloid-specific immune response in these patients. This finding opens up possibilities for new treatments, including using these antibodies and gene-editing techniques to eliminate harmful protein accumulations in the heart and prevent future build-ups.
A research team from UCL and the Royal Free Hospital reported an extraordinary development where three men, previously suffering from heart failure due to the accumulation of harmful, sticky proteins, became asymptomatic after their condition spontaneously improved.
Amyloidosis, a progressive disease that was once considered irreversible, affects the heart. Until now, the outlook for individuals with this disease was bleak, with 50% of patients succumbing to the illness within four years of diagnosis.
The recent study, which took the form of a letter in The New England Journal of Medicine, focuses on three men aged 68, 76, and 82. All three were diagnosed with transthyretin cardiac amyloidosis and subsequently experienced an unexpected recovery. The men’s self-reported improvements were backed up by objective assessments such as cardiovascular magnetic resonance (CMR) scans that demonstrated a clearance of the amyloid proteins in their hearts.
Professor Marianna Fontana, the study’s lead author from the UCL Division of Medicine, expressed the ground-breaking nature of their findings. She stated, “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.”
Furthermore, the team identified an immune response in the three men that targeted amyloid specifically. These unique antibodies were not found in other patients whose disease progressed normally.
Senior author Professor Julian Gillmore, Head of the UCL Centre for Amyloidosis at the Royal Free Hospital, acknowledged that it’s not yet definitively proven if these antibodies prompted the patients’ recovery. However, he noted that their data suggest it’s highly probable and that there is potential for creating such antibodies in a lab for therapeutic use. This research is still in its early stages, though.
Transthyretin (ATTR) amyloidosis results from amyloid deposits composed of a blood protein known as transthyretin (TTR). This condition can be hereditary or non-hereditary, referred to as the “wild-type”. Current NHS treatments aim to alleviate symptoms of heart failure but do not specifically address the amyloid build-up.
The recent advancement in imaging technologies has led to an increase in diagnoses compared to two decades ago. These techniques allow for more precise monitoring of disease progression and can identify cases where the condition has improved, not just stabilized.
The recent study, funded by the Royal Free Charity, started when a 68-year-old man reported an improvement in his symptoms. This led the research team to review records of 1,663 patients diagnosed with ATTR-CM, and two additional cases of improvement were found.
Their recoveries were verified through blood tests, various imaging methods, and in one instance, an exercise capacity evaluation. Imaging scans revealed a near-normal heart function and structure, with nearly all amyloid cleared.
Reviewing the records of the larger patient group, the researchers confirmed that only these three men showed a reversal in their condition. Notably, one patient had a heart muscle biopsy, revealing an unusual immune response surrounding the amyloid deposits. This finding was not observed in biopsies from 286 patients with typical disease progression.
Further investigation revealed the presence of antibodies in these three patients that bound specifically to ATTR amyloid deposits in mouse and human tissue and synthetic ATTR amyloid. Such antibodies were not found in 350 other patients with a normal disease progression.
If these antibodies can be utilized effectively, they could be combined with emerging therapies that suppress TTR protein production. This could enable clinicians to both clear amyloid and prevent further amyloid deposits.
One such therapy is a single intravenous infusion of NTLA-2001, a novel gene-editing therapy based on CRISPR/Cas9. Early trial results, led by Professor Gillmore, indicate that it may halt disease progression.
The UCL Centre for Amyloidosis is one of the leading centers for amyloid research globally. It hosts the NHS National Amyloidosis Centre, the UK’s only amyloidosis-specific center.
Jon Spiers, CEO of the Royal Free Charity, stated, “As an NHS charity, we are proud to support this research. Our priority is to foster early-stage research that brings innovative treatments to patients sooner. This work not only represents a significant breakthrough in understanding cardiac amyloidosis but also opens up new treatment possibilities.”
The Royal Free Charity is the official charity partner of the Royal Free London NHS Foundation Trust, supporting the work of the National Amyloidosis Centre. This study marks the first-ever human trial in which CRISPR/Cas9, a Nobel Prize-winning technology that alters cells’ DNA to insert a new genetic code, has been administered intravenously as a medicine to deactivate a target gene in a specific organ – in this case, the liver, where the TTR protein is produced.
Frequently Asked Questions (FAQs) about Amyloidosis recovery
What is transthyretin cardiac amyloidosis?
Transthyretin cardiac amyloidosis is a progressive heart condition characterized by the accumulation of amyloid proteins in the heart. It was previously considered irreversible and associated with a grim prognosis.
How did the three men in the study recover from transthyretin cardiac amyloidosis?
The exact mechanism behind their recovery is still being investigated. However, the researchers identified a unique immune response in these patients that specifically targeted the amyloid proteins. This immune response may have played a role in clearing the toxic protein build-up and halting further deposition.
What are the implications of this study?
The study’s findings raise the potential for new treatments for transthyretin cardiac amyloidosis. By harnessing the amyloid-targeting antibodies and combining them with gene-editing therapies, it may be possible to clear amyloid and prevent its further accumulation in the heart.
Are there existing treatments for transthyretin cardiac amyloidosis?
Current treatments aim to relieve the symptoms of heart failure but do not directly address the amyloid build-up. However, promising therapies such as gene-silencing techniques that reduce TTR protein concentration in the blood are being trialed to slow down amyloid formation.
What is the role of the UCL Centre for Amyloidosis in this research?
The UCL Centre for Amyloidosis, along with the Royal Free Hospital, conducted this research. It is one of the leading centers for amyloid research globally and includes the NHS National Amyloidosis Centre, specializing in the diagnosis and treatment of amyloidosis.
How can this research benefit patients?
The research offers hope for improved treatment options for individuals with transthyretin cardiac amyloidosis. If the amyloid-targeting antibodies identified in the study can be recreated in a lab, they could potentially be used as a therapy to clear amyloid and prevent its progression. Additionally, gene-editing therapies like CRISPR/Cas9 show promise in stopping disease progression and may provide new avenues for treatment.
More about Amyloidosis recovery
- The New England Journal of Medicine: “Antibody-Associated Reversal of ATTR Amyloidosis–Related Cardiomyopathy”
- University College London (UCL)
- Royal Free Hospital
- UCL Centre for Amyloidosis
- NHS National Amyloidosis Centre
- Royal Free Charity