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HCM is a condition where the heart muscle becomes abnormally thick, making it harder for the heart to pump blood. It affects 1 in 250 people and is a leading cause of sudden cardiac death. The thickening is often caused by mutations in genes related to the heart’s muscle fibres, and over time can lead to scarring (fibrosis), heart failure, or even death.
The genetic roots of HCM have been understood for years, but we are yet to understand why the heart gets so scarred. The new study suggests that part of the answer lies in the body’s immune response.
The immune system’s surprising role
When researchers examined the hearts of deceased HCM patients and animal models with the disease, they found that immune cells had gathered in scarred areas of the heart, particularly in later stages of the disease.
‘These cells, usually known for fighting infections, were playing complex roles in either enhancing or limiting inflammation and scarring,’ said the Radcliffe Department of Medicine’s Ying-Jie Wang, first author of the paper.
‘In particular, we found that immune cells called macrophages, and other myeloid cells were highly active in diseased hearts, but another type of immune cell, called regulatory T cells (or Tregs), appeared to help limit the fibrosis and inflammation.’
Turning the body against the disease
The research team ran a series of experiments using mouse models that closely mimic human HCM. Mice that lacked lymphocytes developed even worse heart scarring and function loss, but when researchers transferred healthy Treg cells into these mice, the heart scarring was significantly lessened, and function was improved.
Even more promising, when the team expanded Treg cells in vivo using a special low-dose immune treatment (involving the molecule interleukin-2), they protected the diseased heart from developing further fibrosis, inflammation was reduced, and further deterioration of heart function was prevented.
Targeting disease progression
Current HCM treatments focus mainly on symptoms - like reducing heart strain or, in some cases, surgical interventions. Some drugs target the heart’s contractile function, but they don’t address the underlying inflammation and scarring. This new approach could complement existing therapies by directly targeting the disease’s progression and possibly reversing scarring.
'This could open up a completely new avenue of treatment for patients who are past the early stages of HCM and starting to develop serious heart scarring and reduced heart function,' said senior author Professor Hugh Watkins, Radcliffe Professor of Medicine and lead of the CureHeart project.
‘It builds a strong case for testing Treg-based therapies in human clinical trials. Such therapies are already being explored for autoimmune diseases and transplant rejection, so repurposing them for HCM could be a quicker path to patient use.
‘If successful in humans, this treatment could offer hope to thousands living with HCM—and possibly change how we treat heart disease more broadly.’
CureHeart is a cutting-edge research project funded by the British Heart Foundation which aims to develop cures for cardiomyopathies using advanced genetic therapies.
The paper, ‘Regulatory T cells attenuate chronic inflammation and cardiac fibrosis in hypertrophic cardiomyopathy’, is published in Science Translational Medicine.