Gene Editing Moves Toward Common Diseases as Cardiologists Urge Stronger Safeguards

Gene therapy is no longer a distant promise of medicine; it is already part of clinical care. Treatments that replace, silence or edit genes are being used in patients today, and the early successes have come in rare genetic disorders such as spinal muscular atrophy and sickle cell disease. Yet researchers are now looking beyond these rare conditions. According to a new perspective published in JAMA Internal Medicine, the field is rapidly moving toward genomic therapies designed to treat common conditions, including high cholesterol, heart disease, obesity and diabetes.

That shift raises difficult questions, and two cardiologists from the University of Michigan Health Frankel Cardiovascular Center have set out to answer them. Eric D. Smith, M.D., and Venkatesh L. Murthy, M.D., Ph.D., who study gene therapy, proposed strategies for determining when genomic therapy is justified. Their perspective, titled “Clinical Framework for Durable Genomic Interventions,” outlines when the potential benefit of gene editing outweighs the possibility of permanent harm, and what safeguards must be in place before these therapies reach large populations.

One of the central distinctions the cardiologists draw is between conventional medications and genomic therapies. Smith explains that conventional medications work only while patients continue taking them, whereas genomic therapies can supply a functional copy of a gene, reduce the activity of a harmful gene, or directly edit a DNA sequence. Because they act at the level of genetic material, many are designed as single-administration, or “one-and-done,” treatments. But Smith cautions that this does not guarantee their benefits will last forever. Many of these therapies rely on viral delivery vehicles, and the body’s immune response often prevents a second dose from being given even if one were needed.

Smith also emphasizes an important boundary for the public to understand. Current gene therapies target somatic cells, meaning any genetic changes are not intended to be passed to future generations. This distinguishes them from germline editing, which would alter inherited DNA. The therapies now moving through research and clinical pipelines are designed to change the genetic material of the treated individual alone, a point the cardiologists argue is essential for framing public discussion as these treatments become more widely discussed.

If a single treatment could eventually prevent conditions like high cholesterol, heart disease, obesity or diabetes, why shouldn’t everyone receive one? Murthy’s answer is that the calculation differs sharply between rare and common diseases. For rare, severe diseases, he says, the case can be relatively straightforward: the unmet need is high, and patients may have few or no effective alternatives. For common conditions, the picture becomes more complex, because genomic therapies may compete with treatments that already work well and can be adjusted or stopped if problems arise.

The population-level mathematics of safety is another concern Murthy raises. Even extremely rare side effects could affect large numbers of people if millions receive treatment. As therapies move from rare diseases to common conditions, he argues, the safety bar must rise accordingly. A risk that might be acceptable for a patient with no other options becomes far harder to justify when the alternative is an effective, reversible daily medication taken by millions of otherwise healthy people.

To guide these decisions, Smith and Murthy have proposed five questions to consider before using a genomic therapy. How severe is the disease? Are effective, reversible alternatives already available? Is the target tissue suitable for a durable, one-time intervention? Is the risk of the delivery method proportionate to the condition being treated? And can safety and effectiveness be monitored over the long term once the therapy reaches large populations? Smith identifies that last question as perhaps the most difficult and urgent of the five, because it concerns what happens after a therapy leaves the controlled environment of clinical trials.

The problem, Smith notes, is that clinical trials are often too small and too short to identify rare complications or problems that emerge years after treatment. Those risks may become visible only after a therapy is used in a much larger population. Existing registries have demonstrated the value of long-term surveillance, but therapies used by millions of people will require independent, standardized systems capable of evaluating safety and effectiveness over time. In the cardiologists’ view, long-term safety monitoring must be built into the way a therapy reaches patients, and genomic medicine needs durable systems for long-term monitoring comparable to those that have proven their worth in other fields.

Are some diseases or biological targets simply not appropriate for permanent gene therapy? Murthy says possibly, arguing that the fact that we can develop a genomic therapy for a condition does not necessarily mean that we should. Many common conditions already have effective treatments that can be adjusted or stopped if problems occur. Because permanent interventions lack that flexibility, they may be poorly suited for targets that require frequent dose adjustments, have a narrow therapeutic window or carry substantial risks when over- or under-corrected. Future genomic therapies may include biological “off-switches” or other mechanisms for reversing their effects, but until those safeguards are proven reliable, the cardiologists argue that reversibility should be viewed as an important clinical benefit.

Cost and access form the final pillar of the framework. Some currently available gene therapies have list prices exceeding $1 million per patient, with several priced substantially higher. While a one-time therapy may make sense for a rare, life-threatening disease, similar pricing models would be difficult to sustain for conditions affecting millions of people. Before genomic therapies move into common diseases, the authors argue, the field must consider not only whether they work, but also whether patients can access them and whether health systems can afford them without worsening disparities. The possibility of a single genetic treatment preventing heart disease for decades is no longer purely hypothetical: early studies are already testing whether a single gene-editing treatment can produce long-lasting reductions in LDL, or “bad,” cholesterol. Before these therapies are used broadly, Smith says, researchers must demonstrate long-term safety, durability, affordability and appropriate safeguards. The goal, he stresses, is not to slow progress, but to ensure these therapies are introduced responsibly as they move from treating rare diseases to potentially millions of patients.

Subject of Research: A clinical framework for evaluating durable genomic therapies as gene editing expands from rare diseases to common conditions

Article Title: Gene editing is coming for common diseases. Are we ready?

Article References: Gene editing is coming for common diseases. Are we ready?. Original publication (Bibliographic details unavailable.)

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Keywords: gene editing, gene therapy, genomic medicine, cardiology, JAMA Internal Medicine, safety monitoring, rare diseases, common diseases, cholesterol, health policy, ethics, Michigan Medicine