These models are crucial to understanding disease mechanisms and identifying new treatment opportunities.The National Institutes of Health has renewed a five-year grant for $1.8 million per year for the University of Alabama at Birmingham Center for Precision Animal Modeling, totaling more than $9 million.
CPAM serves as a resource dedicated to helping UAB researchers understand genetic changes in disease by developing precision disease models that span experimental, cellular and computational systems.
“CPAM gives us the ability to create precise experimental systems that reflect the same genetic alterations (variants) found in patients,” said Matt Might, Ph.D., professor in the Department of Medicine and director of the Hugh Kaul Precision Medicine Institute.
These models are crucial to understanding disease mechanisms and identifying new treatment opportunities.
“By developing more advanced and flexible model systems, we can identify new drug targets and biomarkers much more efficiently and cost-effectively,” said Bradley Yoder, Ph.D., professor and chair in the Department of Cell, Developmental and Integrative Biology and University of Alabama Health Services Foundation Endowed Chair in Biomedical Research. “These complementary platforms will make the pipeline more versatile, efficient and patient-focused, strengthening CPAM’s ability to serve researchers, clinicians and families seeking answers.”
Turning genetic variants into disease models
Since its launch in 2020, CPAM has received more than 185 nominations to study specific disease-associated genetic changes submitted by researchers, clinicians, patient foundations and sometimes patients.
According to Might, “Prior to CPAM, there was no real next step for many patients we now help. They might be told, ‘We think this is the cause, but we can’t be sure’ or ‘We think this could be a therapeutic approach, but we don’t have a way to test it.’”
So far, about 60 percent of these nominations have been selected for further study, with the resulting models generating new knowledge of disease and advancing therapies. These precision systems include whole-organism, cellular and computational models, forming a powerful framework for discovery.
“By studying how a specific genetic variant affects a biological system, from cells to whole organisms, we can connect genes to disease, understand complex, multi-organ effects and evaluate potential therapies,” said Elizabeth Worthey, Ph.D., associate professor in the Department of Genetics. “Running computational, cellular and — when necessary — animal systems helps connect genes to disease, identify complex, multi-organ symptoms and test potential treatments in ways that aren’t yet possible in cell-based systems alone.”
“At CPAM, in many projects, we start with cell-based and computational models to narrow down questions and prioritize hypotheses,” Yoder said. “We only bring in animal models when needed in the effort to improve safety and specificity of therapeutics.”
Advancing precision medicine through genetic modeling
CPAM supports the mission of precision medicine by delivering research models and data that help tailor treatments to an individual’s genetics. This includes helping patients with rare or hard-to-diagnose conditions by building models based on their specific genetic mutations to guide diagnosis and treatment.
“CPAM provides new resources for the scientific research community, forming a robust pipeline to explore disease mechanisms, test hypotheses and prioritize therapeutic strategies,” Yoder said. “These contributions align with and strengthen the broader goals of UAB and NIH — to gain knowledge regarding chronic as well as rare diseases and to improve patient care and health outcomes through innovation and collaboration.”
In a recent case, CPAM identified a new genetic variant linked to an extremely rare muscle disease called X-linked myopathy with excessive autophagy, or XMEA.
Through this discovery, researchers were able to generate new XMEA models, establish collaboration with another rare disease expert and identify a potential repurposed drug that is now being prepared for testing in a small clinical trial.
“This case and similar cases represent a mechanism by which a dearth of knowledge in a particular disease can be assisted by the generation of new precision animal models,” Yoder said.
The renewed funding ensures that CPAM will remain a vital resource for researchers, clinicians and patients seeking to unlock the genetic causes of disease.
“CPAM embodies the ethos of ‘science in the service of patients,’” Might said. “It serves as a source of hope for patients where science has become the next step in their clinical journey.”
CPAM is led by Yoder and co-directors Might and Worthey.