Researchers at The Jackson Laboratory (JAX) have unveiled a new approach to drug discovery that could revolutionize the way we understand and treat diseases. Their recent commentary in the August 14 issue of Nature Biotechnology explains the limitations of studies using traditional mouse models and proposes using genetically diverse mice and mouse and human cells to better predict human responses to drugs and diseases.
For decades, scientists have relied on inbred mice to study human diseases and test new drugs. However, these mice often fail to accurately mimic human conditions, especially in complex diseases such as cancer and diabetes. The FDA’s recent decision to allow alternatives to animal testing through the Modernization Act 2.0 underlines the urgency of finding more reliable solutions.
JAX Mammalian Genetics Scientific Director Nadia Rosenthal, Ph.D., F.Med.Sci and colleagues make a bold claim: it’s not the mice that are the problem, but the lack of genetic diversity in the models used. Relying on a single inbred strain can lead to inconsistent and often unreliable results, creating unnecessary obstacles to finding better therapies for a variety of diseases.
A new, more accurate approach
The researchers propose an integrative solution: combine the use of genetically diverse mouse models with cell-based assays to more accurately match mouse and human data. This approach takes full advantage of the rich genetic resources already available in diverse mouse and human populations to create more accurate and relevant disease models.
“The use of various mouse models has already shown remarkable improvements in mimicking human disease,” says Rosenthal. “This method could revolutionize our understanding of disease progression and patients’ responses to different treatments.”
Real world impact
Studies with various mice have already provided valuable insights into diseases such as heart disease, cancer and diabetes. For example, recent research into chemotherapy side effects has identified genetic factors that influence how patients respond to treatment, leading to more personalized and effective therapies for cancer patients. And heart attacks in humans can lead to variable severity and different types of damage to the heart, such as scarring or dilation, caused by complex genetics that a single inbred mouse strain cannot replicate. However, a genetically diverse panel of mice showed a human-like diversity of results.
This new framework highlights the importance of combining mouse and human data. Although human cell-based tests are useful, they often fall short in capturing the full complexity of human disease. Cells from genetically diverse mouse models help fill this gap, making the findings directly applicable to patients in the real world.
A call to action
The authors argue for a new, balanced approach that respects ethical considerations while maximizing scientific benefits. They urge the community to embrace experimental designs that take into account genetic diversity and environmental factors, and move away from standardized but limited mouse and cellular models. By combining the strengths of both in vitro and in vivo systems, researchers will be able to develop more effective, humane methods for studying human diseases and testing new treatments.
