Researchers at University of Michigan Health are proposing safety guidelines for gene therapies designed to treat common diseases like high cholesterol, heart disease, obesity, and diabetes.
Eric D. Smith and Venkatesh L. Murthy, cardiologists at the University of Michigan Health Frankel Cardiovascular Center, published a perspective in JAMA Internal Medicine outlining how doctors and researchers should evaluate genomic therapies. Gene therapies can introduce working copies of genes, silence harmful genetic activity, or modify DNA directly. Unlike daily medications, some genetic treatments are designed to work after a single administration.
Smith and Murthy explain that current gene therapies typically use modified viruses to deliver genetic instructions into cells. The immune system can recognize these delivery vehicles and mount a response, making it difficult to administer the same treatment again if benefits fade. Current therapies target somatic cells, not germline cells, so genetic changes are not inherited.
The researchers identify several challenges. Common diseases already have established treatments that doctors can adjust or discontinue if side effects develop. A permanent genetic change offers no such flexibility. Murthy notes that a rare serious side effect could still harm many patients if a therapy reaches millions of people.
Clinical trials typically involve small groups monitored for limited periods, which may miss rare complications or problems developing over years. Smith argues that long-term monitoring must be built into how gene therapies enter medical practice, requiring patient registries and standardized, independent monitoring systems operating at large scale.
Some conditions may be unsuitable for permanent treatment altogether. Murthy emphasizes that the ability to alter a genetic target does not automatically make doing so the best medical decision. Some diseases require careful dose adjustments over time, and the difference between effective treatment and harmful one can be extremely small.
Cost presents another barrier. Some existing gene therapies cost above $1 million per patient. Smith and Murthy argue that affordability and access must be part of discussions from the beginning to avoid creating healthcare inequalities.