Gene Therapy for Cardiomyopathies Presents Promising Alternative to Current Treatment

Cardiomyopathies currently have no cures, but many of these disorders are prime candidates for gene therapies.

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Treatments for cardiomyopathy may address the symptoms of the disease or slow the progression of it but are not curative. In addition to pharmacological treatment options, patients can undergo surgery or make lifestyle changes to address their cardiomyopathy.

However, gene therapy may present a life-changing option for a cure. In a new review published in the International Journal of Molecular Sciences, authors from Italy reviewed the ongoing clinical trials and future goals.

“Traditional treatment modalities, including medications, lifestyle modifications, and, in some cases, surgical interventions, have offered varying degrees of success but fall short in addressing the underlying genetic causes of these disorders,” the authors wrote. “As our understanding of the genetic basis of cardiomyopathies increases, gene therapy emerges as a revolutionary approach with the potential to transform the landscape of cardiac care.”

Cardiomyopathy encompasses any disorder that affects the heart muscles. These conditions cause the heart to lose its ability to pump blood and can cause arrythmias. The condition tends to be progressive.

While more gene therapies gain approval, the cost of these therapies can be extremely high. The Institute for Clinical and Economic Review (ICER) noted in its report “Managing the Challenges of Paying for Gene Therapy: Strategies for Market Action and Policy Reform,” published earlier this year, that prices for gene therapies are now above $3 million with spend in the United States for these treatments estimated to be between $35 billion and $40 billion.

While small numbers of patients are currently being treated by gene therapies, larger populations are on the horizon, ICER noted. Heart disease is prevalent in the U.S. with as many as 1 in 500 adults potentially having a cardiomyopathy.

Among the cardiomyopathies, cardiac amyloidosis currently has gene therapies approved. Onpattro (patisiran), Amvuttra (vutrisiran), Tegsedi (inotersen) and Wainua (eplontersen) are all gene silencing agents that treat polyneuropathy caused by hereditary transthyretin-mediated amyloidosis.

The researchers conducted a literature search to identify research into the use of gene therapy in cardiomyopathies. Among the types of gene therapies being studied are gene replacement therapy, which would substitute a malfunctioning gene causing a loss-of-function mutation impacting cardiac function; genome editing, which could correct both gain-of function and loss-of-function mutations by altering the cell’s natural genomic sequence; and gene silencing, which modulates gene expression.

They also identified ongoing trials for rare heart diseases, including Friedreich ataxia, Danon disease, Fabry disease and Pompe disease.

• Danon disease — a gene therapy utilizing RP-A501 is ongoing with a small number of male subjects 8 years old and older. The trial is expected to complete in 2025.
• Fabry disease — there are several ongoing studies assessing the safety and effectiveness of gene therapy.
• Pompe disease — the goal of the 5 ongoing clinical trials is to provide a functional copy of the enzyme of acid alpha-glucosidase by using adenoviruses as vectors.
• Friedreich ataxia — there is one ongoing trial evaluating a gene therapy for. The trial is evaluating the treatment in approximately 25 patients and is expected to end in 2029.
• Arrhythmogenic cardiomyopathy — there are three trials that have started evaluating gene therapies with results expected as early as 2026.
• Hypertrophic cardiomyopathy — there is only one ongoing trial.

With gene therapies, it’s important that ethical issues are considered, the authors wrote. For instance, the patients receiving them have to fully understand the procedure, its risks, its advantages and the uncertainties. In addition, the price of gene therapies raises ethical concerns about accessibility.

“Gene therapy is constantly evolving and presents a highly promising therapeutic alternative in the field of cardiomyopathies,” the authors concluded. “With ongoing research, validation, and development, these advancements may lead to improved treatment effectiveness, customized therapies for individual patients, and ultimately enhance the quality of life for those affected by cardiomyopathies.”