by A groundbreaking study conducted by researchers at NYU Grossman School of Medicine and scientists at Rocket Pharmaceuticals has shown that gene-based therapy has the potential to prolong survival in individuals with arrhythmogenic right ventricular cardiomyopathy (ARVC), a rare inherited heart disorder. ARVC is characterized by the progressive weakening of the muscular walls of the heart, which puts patients at risk of dangerous irregular heartbeats. The loss of function of the plakophilin-2 (PKP2) gene has been identified as a significant contributor to the development of ARVC.
The PKP2 gene is responsible for producing a protein that holds heart tissues together. When the gene is defective and fails to produce a functional protein, fibrous and fatty tissue accumulates within the heart’s walls, ultimately leading to their weakening. In addition, individuals with ARVC may experience irregular heartbeats or, in severe cases, heart failure. While current treatments can help manage the symptoms and restore normal heart rhythm, there is no cure for ARVC.
The researchers discovered that mice engineered to lose PKP2 gene function died within six weeks when left untreated. However, those mice that received a single dose of gene therapy, which involved the replacement of the defective gene with the healthy version, lived for more than five months. Furthermore, the mice that received the gene therapy showed a significant reduction in the buildup of fibrous tissue, ranging from 70% to 80%, depending on the dosage administered.
According to Chantal van Opbergen, Ph.D., a postdoctoral research fellow at NYU Langone Health and co-lead author of the study, “Our findings offer experimental evidence that gene therapy targeting plakophilin-2 can interrupt the progression of a deadly heart condition.”
The advanced stages of ARVC often involve irreversible heart damage, and in some cases, a heart transplant may be necessary. Therefore, researchers have long been searching for ways to slow the progression of the disease and minimize tissue loss.
In a previous study by the NYU Langone team, they explored the mechanisms by which defects in the PKP2 gene can lead to life-threatening irregular heartbeats (arrhythmias), which are observed in some individuals with ARVC.
For this new study, the researchers utilized a mouse model of ARVC, in which the PKP2 gene was modified to be non-functional. The researchers used an adeno-associated viral vector as a delivery mechanism to introduce the healthy gene into the cardiac cells, providing the necessary PKP2 protein therapy.
Adeno-associated viral vectors are non-replicating particles that utilize the natural infection process to deliver the desired gene into target cells. Once inside the cell, the viral vectors do not multiply but enable the heart cells to produce the normal protein with the healthy gene in place. The viral vector used in the study was designed and developed by Rocket Pharmaceuticals.
This groundbreaking study provides hope for individuals with ARVC, as gene-based therapy shows great potential in slowing the progression of this life-threatening heart condition. Further research and clinical trials are needed to fully assess the efficacy and safety of this treatment, but it represents a significant step forward in the field of gene therapy for heart diseases.
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1. Source: Coherent Market Insights, Public sources, Desk research
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