In last week’s episode of The Genetics Podcast, Patrick Short spoke with Dr. Eric Adler, Professor of Medicine at UC San Diego and Chief Medical Officer at Lexeo Therapeutics. Dr. Adler’s work bridges the gap between cutting-edge gene therapy research and patient-centered cardiology, particularly for those with genetic heart diseases like Danon disease.
The path to gene therapy in cardiomyopathy
Dr. Adler has spent the last two decades studying cardiomyopathy, a disease that affects the heart muscle and can lead to heart failure. His career first began with a focus on regenerative medicine, specifically pluripotent stem cell research. Then, Dr. Adler saw the opportunity to use patient-derived stem cells to model rare cardiovascular diseases in the lab.
This approach led him to study Danon disease, a rare genetic cardiomyopathy. Many of his early patients were misdiagnosed with other conditions, prompting work on stem cell models and sequencing techniques to confirm their diagnoses. As more patients reached out to him, desperate for answers and treatment, Dr. Adler’s work turned toward developing a targeted gene therapy for the condition.
The role of gene therapy in treating heart disease
Gene therapy is opening new possibilities for treating genetic forms of cardiomyopathy. In Danon disease, where a single genetic mutation causes a loss of function, replacing the missing gene with gene therapy offers a direct path to treatment.
Dr. Adler and his team initially used viral vectors to introduce genetic material into patient-derived stem cells. The breakthrough moment came when they realized that these viral vectors could not only correct disease phenotypes in a dish but also serve as the basis for a potential therapy. This realization led to the development of a gene therapy treatment aimed at replacing the faulty gene in Danon disease patients.
One of the key advantages of gene therapy in cardiology is that heart cells do not divide frequently. Once a gene therapy is delivered to the heart using an adeno-associated virus (AAV), it has the potential to remain active for years, providing a long-term therapeutic effect.
Expanding genetic therapies to other cardiovascular diseases
Dr. Adler’s work has expanded beyond Danon disease to include other genetic cardiomyopathies. As he continued to genetically test his patients, he discovered that many individuals labeled as having “idiopathic” (cause unknown) cardiomyopathy actually had underlying genetic mutations.
This revelation has outlined the need for more widespread genetic testing in cardiovascular medicine. By identifying the genetic drivers of heart disease earlier, physicians can intervene before irreversible damage occurs.
The broader challenges in cardiovascular health
Beyond genetic disease, cardiovascular healthcare faces significant challenges. While lots of progress is being made in reducing heart disease mortality through public health measures—such as smoking cessation programs and cholesterol-lowering medications—the past two decades have seen worsening trends.
Dr. Adler attributes this to a combination of factors, including obesity rates, poor dietary habits, and increasing drug and alcohol use. He also points to growing distrust in medicine, which has led some patients to avoid preventive care and evidence-based treatments.
Polygenic risk scores, which assess a person’s genetic predisposition to heart disease, could offer another avenue for improving outcomes. By integrating genetic risk factors with lifestyle changes, doctors could provide more personalized recommendations for heart disease prevention.
The future of gene therapy in cardiovascular medicine
At the end of the episode, Dr. Adler talks about a future where gene therapy is not just used to treat rare genetic heart diseases but also plays a role in preventing common forms of heart failure. While we are not yet at the point where gene therapy can be used as a preventive, advancements in precision medicine continue to push the field closer to that reality.
He also highlighted the need for greater engagement between the medical community and the public. Misinformation about medical treatments, including gene therapy, is a growing concern. To ensure that patients have access to life-changing therapies, it is essential for doctors and researchers to communicate transparently and effectively with the public.
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