Researchers
from Queen Mary University of London have found that a medication originally
developed for glycemic control can reverse serious heart damage—not by
controlling blood sugar as originally intended, but by retraining the immune
system to protect the heart from within.
The findings, published this month in Nature Cardiovascular
Research, reveal a previously
unknown link between immune dysfunction and the metabolic deterioration seen in diabetic hearts—and point
toward an entirely new class of cardiac treatment.
Diabetic cardiomyopathy is one of the most serious and
least-discussed complications of type 2 diabetes. It develops independently of
blocked coronary arteries, instead arising from a combination of chronic inflammation, metabolic dysfunction, and structural damage, which progressively
stiffens and weakens the heart muscle. Patients develop diastolic
dysfunction—meaning the heart struggles to relax and fill properly—leaving them
increasingly vulnerable to heart failure and far more likely to suffer severe
damage if they have a heart attack.
Despite its prevalence, no approved therapies specifically target metabolism of diabetic hearts. Standard diabetes treatments regulate blood sugar levels, but largely leave the heart's underlying deterioration untouched.
How an abandoned diabetes drug helps
The drug AZD1656 was originally developed by Astra Zeneca to improve blood
sugar control in people with type 2 diabetes, but didn't work well for that
purpose. Rather than targeting blood sugar, subsequent research revealed that
the drug can rebalance the immune system by helping regulatory T (Treg)
cells (a type of protective immune cell) move around the body more
effectively.
This discovery prompted an international team of researchers, led by
Professor Dunja Aksentijevic of the William Harvey Research Institute at Queen
Mary University of London, to investigate whether AZD1656's immune effects
could be used to advantage in the diabetic heart.
The team found that AZD1656 corrects the Treg cell imbalance and can
reverse serious heart damage in diabetic patients, a completely different
mechanism than any described to date. They show that AZD1656 boosts the ability
of protective immune Treg cells to travel into the heart, where they calm
inflammation, reduce post-infarct scarring, and—remarkably—allow the heart's
disrupted energy systems to recover almost to normal.
Heart function gains beyond blood sugar
The study also showed that treatment dramatically improved heart function,
cut heart attack damage, and restored the heart's metabolic profile to
near-healthy levels. Crucially, none of this was explained by changes in blood
sugar, body weight, liver, fat or muscle metabolism.
Dunja Aksentijevic, Professor of Cardiovascular Physiology and Metabolism
at Queen Mary University of London and a Wellcome Trust Research Fellow, said,
"This work stems directly from my Wellcome Career Re-Entry Fellowship and
establishes aberrant
immunometabolic signaling as a promoter of cardiac remodeling in type 2
diabetes. Targeting this axis by enhancing the migratory capacity of regulatory
T cells improved diabetic cardiomyopathy, thus opening a new therapeutic
direction for the treatment of hundreds of millions of people worldwide living
with type 2 diabetes."
Source: Drug that targets immune cells shows potential as new treatment for diabetic heart disease


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