An international study led by researchers at the Sanford Burnham Prebys Medical Discovery Institute has uncovered the molecular mechanism behind lithium’s effectiveness in treating bipolar disorder.
The study, published in the influential journal Proceedings of the National Academy of Sciences, utilized human stem cells to map lithium’s response pathway. These results are the first to explain the molecular basis of the disease, and may support the development of a diagnostic test for the disorder as well as predict the likelihood of patient response to lithium treatment.
The discovery, announced Monday, may also provide the basis to discover new drugs that are safer and more effective than lithium.
“Lithium has been used to treat bipolar disorder for generations, but up until now our lack of knowledge about why the therapy does or does not work for a particular patient led to unnecessary dosing and delayed finding an effective treatment. Further, its side effects are intolerable for many patients,” said Evan Snyder, director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys and senior author of the study.
Using stem cells created from lithium-responsive and non-responsive patients, researchers discovered a difference in the regulation of CRMP2, a protein that in turn regulates neural networks. Lithium restored the normal activity of this protein.
“Importantly, our findings open a clear path to finding safe and effective new drugs. Equally as important, it helped give us insight into what type of mechanisms cause psychiatric problems such as these,” he added.
Bipolar disorder is a mental health condition causing extreme mood swings that include emotional highs and lows and affects approximately 5.7 million adults in the U.S. Only one-third of patients respond to lithium treatment, and its effect is only found through a trial-and-error process that takes months—and sometimes years—of prescribing the drug and monitoring for response.
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