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From mice to man
BETHESDA, Md.—Researchers have discovered that a hormone, fibroblast growth factor 21 (FGF21), is extremely elevated in mice with liver disease that mimics the same condition in patients with methylmalonic acidemia (MMA), a serious genomic disorder.
Based on this finding, medical teams treating patients with MMA will be able to measure FGF21 levels to predict how severely patients' livers are affected and when to refer patients for liver transplants. The findings also might shed light on more common disorders such as fatty liver disease, obesity and diabetes by uncovering similarities in how MMA and these disorders affect energy metabolism and the function of mitochondria.
The study was conducted by researchers at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and published Dec. 6 in JCI Insight.
“Findings from mouse studies usually take years to translate into healthcare treatment, but not in this case,” said Dr. Charles P. Venditti, senior author and a senior investigator in the NHGRI Medical Genomics and Metabolic Genetics Branch. “We can use this information today to ensure that patients with MMA are treated before they develop severe complications.”
The NHGRI team created a new mouse model and used it to discover key pathways that were affected during a fasting challenge to model a metabolic crisis in a patient with MMA. It enabled them to identify markers that they could then measure in MMA patients to assess the severity of the dysfunction in their mitochondria, specifically in the liver.
The NHGRI team will use FGF21 measurements along with other tests presented in the study in the design of upcoming gene-based clinical trials that the lab has worked on for many years. The NHGRI team will next assess the role of FGF21 pathways in other symptoms seen in MMA.