New Arena of Treatment Designed For Genetic Heart Disease Variant

Hybrid gene therapy holds therapeutic efficacy in a genetic heart condition where the heart rhythm can potentially cause fast and chaotic heartbeats.

Hybrid gene therapy holds therapeutic efficacy in long QT syndrome, as per the first preclinical, proof-of-concept study by researchers at Mayo Clinic, published in the journal Circulation.

Long QT syndrome is a genetic heart condition where the heart rhythm can potentially cause fast and chaotic heartbeats. These rapid heartbeats might trigger people to suddenly faint, have seizures, and can be fatal due to sudden cardiac death.

Long QT Syndrome - Causes, Symptoms, Diagnosis, Treatment & Prevention
Long QT syndrome is a rare congenital heart condition characterized by prolonged QT intervals and can cause sudden cardiac deaths.

‘Hybrid gene therapy holds therapeutic efficacy in long QT syndrome, a genetic heart condition where the heart rhythm can potentially cause fast and chaotic heartbeats. This therapy may be a promising strategy for long QT syndrome. This could also open the door for treatment formulation for almost any sudden death-predisposing autosomal dominant genetic heart disease.’

Type 1 long QT syndrome, or LQT1, is the most common subtype, caused by pathogenic variants in the KCNQ1 gene. The prevalence of long QT syndrome is about 1 in 2,000. High-risk patients, when untreated, have an estimated 10-year mortality of 50%.

Two Beating heart cells, reengineered from the blood samples of patients with type 1 long QT syndrome were included as in-vitro model systems by the study team. The potential efficacy of the gene therapy was studied.

Hybrid Gene Therapy in Long QT Syndrome

The whole KCNQ1 gene rather than specific LQT1-causative mutations was targeted. This makes the study applicable to all patients with long QT syndrome 1, regardless of their specific disease-causing variant.

"Gene therapy is an emerging area of interest for treating a variety of genetic heart diseases in general and long QT syndrome in particular. We designed and developed the first suppression and replacement KCNQ1gene therapy approach for the potential treatment of patients with type 1 long QT syndrome", says Michael Ackerman, M.D. Ph.D., Mayo Clinic genetic cardiologist and director of Mayo Clinic's Windland Smith Rice Comprehensive Sudden Cardiac Death Program and senior author of the study.

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Current therapies, like beta-blockers and defibrillators (a more invasive therapy), have their own limitations, risks and an array of unwanted side effects despite substantial improvements made in the management of the long QT syndrome over the past two decades.

Genes contain DNA that controls the body's form and function. Hence gene therapy offers the treatment of the diseases by altering the specific genes in a diseased patient's cells rather than using drugs or surgery. It replaces the faulty genes or adds a new gene to try to treat the disease.

Ectopic Heartbeat - Causes, Symptoms, Diagnosis, Treatment, Complications
Ectopic heartbeats are small changes in regular, normal heartbeats. These changes cause either a skipped or extra heartbeat.

This study for the first time creates the hybrid gene therapy (simultaneous out with the old, in with the new) for any form of genetic heart disease.

"If the therapeutic efficacy of this 'disease-in-the-dish' gene therapy trial with KCNQ1 can be replicated in a nonhuman, animal model of long QT syndrome, then suppression-replacement (hybrid) gene therapy may be a promising strategy for long QT syndrome in general and in theory almost any sudden death-predisposing autosomal dominant genetic heart disease. Of course, we still have a long way to go from nearly curing a patient's heart cells in the dish to effectively treating the whole person. Nevertheless, we are excited by this first critical milestone and look forward to the next step", says, Dr. Ackerman.

The approach to replace and fix mutated genes in a wide range of genetic disorders is also being investigated by the team.

Source-Medindia