Heart failure affects more than six million people in the United States. Some patients receive left ventricular assist devices (LVADs), mechanical pumps that reduce strain and allow the heart to rest. Although LVAD support can enable recovery, only a subset of patients regain meaningful heart function and the biological reasons for this difference have been unclear.
In a study published in the Journal of the American Heart Association, researchers including Junco Warren of Virginia Tech’s Fralin Biomedical Research Institute at VTC and Stavros Drakos of the University of Utah analyzed heart tissue from 19 patients. They compared samples taken before LVAD implantation with samples taken later during device removal or transplantation, using tissue from the left ventricular apex. Patients were classified as responders or non-responders based on improvements in heart function.
The team found that PERM1, a muscle-enriched protein that helps regulate how heart cells produce and use energy, was reduced in all patients before treatment. After LVAD support, PERM1 returned to near-normal levels only in the patients whose hearts recovered, while it remained suppressed in non-responders. The strong correlation between PERM1 levels and improved cardiac function suggests PERM1 is a useful molecular signal of recovery, although researchers do not yet know whether PERM1 drives recovery or simply reflects it.
Previous work from Warren’s lab showed that increasing PERM1 improved heart function in experimental models and prevented heart failure in preclinical studies. To advance potential treatments, Warren and colleagues have co-founded a company to develop PERM1-based gene therapies. Funders of the work included the National Institutes of Health, the American Heart Association, the US Department of Veterans Affairs, the Nora Eccles Treadwell Foundation, and internal Fralin funding.
Difficult words
- implantation — surgical placement of a device into the body
- transplantation — surgical transfer of an organ into a new body
- apex — the tip or pointed end of an organ
- responder — a patient whose condition shows measurable improvementresponders, non-responders
- regulate — to control or adjust a biological process
- suppress — to reduce or keep at a lower levelsuppressed
- gene therapy — medical treatment that alters cell function using DNAgene therapies
Tip: hover, focus or tap highlighted words in the article to see quick definitions while you read or listen.
Discussion questions
- What advantages and risks might arise from developing PERM1-based gene therapies? Give reasons.
- Why do you think PERM1 levels returned to near-normal in some patients but remained low in others? Suggest possible explanations.
- How could classifying patients as responders or non-responders influence future treatment choices for heart failure?
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