Plate Nº 25 · recorded October 13, 2026
Health & Medicine ResearchReported finding
Blocking One Enzyme Reawakens Heart Repair in Mice
A Sanford Burnham Prebys team used malonate to block succinate dehydrogenase in mouse hearts, reawakening dormant regeneration across muscle and scar-forming cells.
By James Calloway3 min read629 words
In brief
- More than 800,000 Americans experience a heart attack each year, per the research team.
- The study appeared in Nature Cardiovascular Research in 2026, DOI 10.1038/s44161-026-00881-9.
- Malonate works by blocking an enzyme called succinate dehydrogenase in heart cells.
- Blocking that enzyme in cardiac fibroblasts, not just heart muscle cells, drove the biggest functional gains.
- Newborn mice can regenerate heart tissue for about a week after birth.
A single injected metabolite reawakened dormant repair programs in adult mouse hearts, Sanford Burnham Prebys researchers report. The treatment cut scar tissue and improved cardiac function after induced heart attacks — a finding aimed at the more than 800,000 Americans who suffer one each year.
What does the treatment actually do?
The adult human heart is famously bad at fixing itself. Newborn mice, however, can regenerate heart tissue for about a week after birth. Beyond that window, the repair machinery goes quiet — but it isn't gone.
The researchers used a metabolite called malonate to block an enzyme, succinate dehydrogenase, in mouse heart cells. That flip re-set the cells' energy production to something resembling the newborn state. The cells started dividing again.
"Normally, mice lose the ability to regenerate their hearts just like humans and other mammals," said Ahmed Mahmoud, Ph.D., the senior author and interim director at Sanford Burnham Prebys' Center for Cardiovascular and Muscular Diseases. "After our treatment, we observed cardiac cells proliferating once again along with the formation of new blood vessels and a reduction in scar tissue that normally follows a heart attack."
Which cells actually matter?
Here's where the result gets interesting — and complicates the team's own expectations. The investigators first assumed heart muscle cells, cardiomyocytes, were the main event. Blocking succinate dehydrogenase there produced a short burst of proliferation. That alone didn't improve function.
Blocking the enzyme in cardiac fibroblasts — the connective tissue cells that lay down scar — was different. Those cells stayed quieter. Scar shrank. Heart function improved.
"We were somewhat cardiomyocyte-centric in our initial hypotheses," said co-first author Dakota Nuttall, a Ph.D. student in the Mahmoud lab. "The results demonstrated the importance of both cell types for successful regeneration and recovery."
"It is a multicellular effect that's driving regeneration, which is something we couldn't fully appreciate until we isolated the effects of metabolic reprogramming in different cell types," Mahmoud added.
What did the cells actually change?
The team used sequencing to measure gene expression and DNA accessibility in treated mice. In heart muscle cells, regions of DNA tied to regeneration and cell-cycle genes opened up. In fibroblasts, scar-forming programs got dialed down.
"We found that regions of DNA associated with pro-regenerative and cell cycle genes became more accessible in heart muscle cells, making it easier for the cells to activate these programs," said co-first author Yi Fan, Ph.D., a postdoctoral associate in the Mahmoud lab. "The other most pronounced change was a suppression of scar-forming programs in connective tissue cells known as cardiac fibroblasts."
DNA is wound on biological spools called histones. Tags on those spools determine which genes stay readable. In cardiomyocytes, an activating mark lit up regeneration genes. In fibroblasts, silencing marks turned down scarring genes.
What does this change for patients?
For now: not much. This is mouse work. The 2026 Nature Cardiovascular Research paper builds on the same team's earlier findings and traces the mechanism more carefully. No human trials are underway.
Mahmoud's group aims there. "Our long-term goal is to translate this concept toward clinical testing and ultimately develop a therapy for the more than 800,000 people in the U.S. who experience a heart attack each year," he said.
A few caveats worth flagging. Malonate is a research tool, not a drug. The therapy temporarily inhibits succinate dehydrogenase, then wears off. Sustained genetic disruption of the enzyme did not help — and might harm — mature heart function. The team hasn't tested the treatment in larger animals.
The takeaway: dormant repair in the adult heart looks real. A metabolic lever can wake it. Whether that lever pulls cleanly in people is the next decade's question.
via Medical Xpress (Source)
More from James Calloway
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Staff writer covering regulation, policy and their impact on general science news at SciBeat.
224 articles
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