Top Things to Know: Gene Therapy in Cardiovascular Disease
Published: November 11, 2024
- Many cardiovascular diseases, the leading cause of morbidity and mortality worldwide, are caused by damaging DNA variants and require lifelong treatments that mitigate but do not cure disease.
- Clinical genetic testing can precisely define disease-causing variants and enable the application of emerging genetic therapies to halt or cure disease.
- Gene therapies deliver exogenous genes to supplement insufficient protein levels or use gene editors to correct, delete, or modify sequences that cause monogenic disorders.
- Gene therapies do not currently aim to alter multiple common variants that cause polygenic disorders.
- Significant challenges remain for the effective delivery of gene therapies to specified cells.
- Non-infectious adeno-associated viruses are effective delivery agents for gene therapies but with distinct limitations. Non-viral delivery vectors overcome many issues, but uptake by cardiomyocytes remains limited.
- Many first-in-human gene therapy trials are in progress and anticipate important clinical risks, including tissue-specific targeting, vector-associated adverse events, off-target effects, and treatment durability.
- Ongoing trials offer transient treatments by supplementing protein-coding sequences for insufficient proteins such as LAMP2 and MYBPC3 in genetic cardiomyopathies and DNA therapies, which will cause permanent effects in recipient cells – providing a potential one-and-done intervention.
- Gene therapies raise societal and regulatory issues, including long-term monitoring, high cost, equitable access, and ethical concerns.
- Educating clinicians, patients, and society is critical to understanding genetic concepts, appropriately interpreting genetic test results, and advancing gene therapies to benefit patients and reduce the burden of cardiovascular disease.
Citation
Kim Y, Landstrom AP, Shah SH, Wu JC, Seidman CE; on behalf of the American Heart Association. Gene therapy incardiovascular disease: recent advances and future directions in science: a science advisory from the AmericanHeart Association. Circulation. Published online November 11, 2024. doi: 10.1161/CIR.0000000000001296