Gene Therapy Breakthrough Shows Promise for Heart Repair
Heart attacks remain a major global cause of death and long-term disability. A key issue is the permanent loss of heart muscle cells (cardiomyocytes), as the adult heart has minimal capacity to regenerate. Most current treatments focus on managing symptoms rather than reversing the actual tissue damage, often leading to chronic heart failure.
Researchers at the Lewis Katz School of Medicine at Temple University have unveiled a promising new strategy to repair damaged heart tissue using a gene known as PSAT1, which is typically inactive in adults. Their findings, published in Theranostics, demonstrate how delivering PSAT1 through synthetic modified messenger RNA (modRNA) can jumpstart regeneration in the heart following a heart attack.
Under the leadership of Dr. Raj Kishore, the research team reactivated PSAT1 in mice by injecting PSAT1-modRNA directly into the heart after injury. Results showed significant improvements, including increased heart muscle cell growth, reduced scarring, better blood vessel formation, and improved heart function compared to untreated mice.
Mechanistically, PSAT1 activates the serine synthesis pathway (SSP)—a key metabolic route linked to cellular survival and stress resistance. It also promotes β-catenin signaling, essential for heart cell regeneration. Interestingly, PSAT1 itself is controlled by YAP1, a known driver of tissue repair. Blocking SSP eliminated the benefits, confirming its central role.
Unlike viral gene therapies, modRNA doesn’t integrate into the DNA, reducing risks of long-term complications. Having already transformed vaccine development, this technology now offers new hope for cardiac healing.
While still in early testing, this approach may shift the future of heart disease treatment—from managing damage to actively repairing the heart at its source.
