A groundbreaking gene therapy has shown remarkable potential in reversing heart failure and improving cardiac function, as evidenced by an extensive study conducted on animals.
This cutting-edge treatment not only enhances the heart’s ability to pump but also leads to a significant increase in survival rates, a development that experts characterize as an unprecedented recovery of heart function.
Potential Revolution in Heart Failure Treatment
Historically, heart failure has been viewed as a permanent condition.
Medical approaches, especially in the absence of a heart transplant, have typically focused on relieving the heart’s burden and slowing the progression of the disease.
However, if clinical trials reflect the positive outcomes observed in this study, this gene therapy could revolutionize treatment options for the estimated one in four people likely to develop heart failure in their lifetime.
The research hones in on an essential cardiac protein called cardiac bridging integrator 1 (cBIN1).
Previous studies revealed that patients suffering from heart failure have significantly lower levels of cBIN1, and this decline correlates strongly with the severity of their condition. Dr. Robin Shaw, MD, PhD, who leads the Nora Eccles Harrison Cardiovascular Research and Training Institute at the University of Utah and is a co-senior author on the study, emphasized that diminished levels of cBIN1 often indicate poor prognoses for patients.
This realization propelled researchers to investigate the potential benefits of restoring cBIN1 levels.
Successful Gene Therapy in Animal Models
To tackle this issue, the team employed a harmless virus commonly used in gene therapy to deliver an extra copy of the cBIN1 gene directly to heart cells.
By injecting this virus into the bloodstream of pigs diagnosed with heart failure, they successfully targeted the gene to the necessary cardiac cells.
In their model of heart failure, untreated pigs generally do not survive beyond a few months.
However, all four pigs receiving the gene therapy thrived for the entire six-month duration of the study, an impressive outcome.
Moreover, the therapy not only halted the progression of heart failure but also facilitated improvements in critical indicators of heart function.
This finding points toward the possibility of recovery in the damaged heart tissue.
Dr. Shaw highlighted the rarity of such reversals in cardiac damage, describing the efficacy seen in this research as groundbreaking within the field of heart failure.
While prior treatments have achieved minor enhancements in heart function—between 5% and 10%—the cBIN1 gene therapy delivered a striking 30% improvement.
Looking Forward: Clinical Trials and Future Implications
As time went on, treated hearts exhibited greater efficiency in blood pumping, which is a key metric for assessing heart failure severity.
Although these measurements didn’t completely match those of healthy hearts, they showed significant improvement.
Additionally, the structure of the treated hearts began to resemble that of non-failing hearts, with less dilation and thinning.
Remarkably, even under the stress that originally led to heart failure, the gene therapy enabled the hearts to regain normal pumping functions.
According to Dr. TingTing Hong, MD, PhD, an associate professor of pharmacology and toxicology at the University of Utah and another co-senior author, despite the stresses associated with heart failure, the treated animals exhibited remarkable recovery and stabilization in their heart function.
This phenomenon, known as reverse remodeling, signifies a return to a healthier state.
The researchers believe that cBIN1’s ability to improve heart function is linked to its role as a structural scaffold that interacts with various proteins essential for cardiac muscle activity. Dr. Jing Li, a CVRTI associate instructor, explained that cBIN1 acts as a central signaling hub, coordinating multiple downstream proteins and thereby aiding in the restoration of crucial cellular functions within the heart.
On a microscopic level, the gene therapy appeared to improve cardiac function too, revealing better-organized heart cells and protein structures.
The research team is optimistic that the role of cBIN1 as a crucial regulator of heart cell architecture will enhance the efficacy of the gene therapy, potentially ushering in a transformative approach to treating heart failure.
Partnering with TikkunLev Therapeutics, the researchers are refining the gene therapy for human use and have plans to seek FDA approval for clinical trials by fall 2025.
While there is excitement surrounding these findings, the therapy will still need to undergo toxicology assessments and additional safety evaluations.
Additionally, it is unclear whether the treatment will be effective for individuals who have built natural immunity to the virus used.
Despite these uncertainties, the research team remains hopeful. Dr. Hong noted that findings from large animal studies closely resembling human physiology could lead to significant breakthroughs in managing a condition affecting over six million Americans.
They are optimistic that this innovative gene therapy could pave the way for a cure for heart failure.
Source: ScienceDaily