Researchers discovered the 100-fold accumulation of GAA occurs when tumors hyperactivate the enzyme that creates GAA. With cancer cells oversaturated, the GAMT enzyme can’t convert the extra GAA into creatine. Excess GAA is released into the tumor microenvironment and stimulates neurons that promote tumor growth.
GAA accumulation in these tumors mimics a known inborn error of metabolism called GAMT deficiency that—like high-grade gliomas—results in seizures and neurological symptoms.
“Our work addresses a long-standing question in cancer neuroscience. We knew there is increased activity of neurons in brain tumors, but we had an incomplete understanding of how brain tumors cause that increase in activity,” said study leader Samuel McBrayer, Ph.D., assistant professor in CRI and of pediatrics.