NARSAD Grantee Finds Experimental Compound Reverses Schizophrenia Symptoms in Mice

Akira Sawa, M.D., Ph.D., expert on schizophrenia research
Akira Sawa, M.D., Ph.D.

In new research led by 2011 NARSAD Distinguished Investigator Grantee Akira Sawa, M.D., Ph.D., an experimental anticancer medication has been found to reverse symptoms of schizophrenia and to restore some lost brain cell function associated with the illness in animal models. Working with adolescent mice, Dr. Sawa and colleagues at The Johns Hopkins University School of Medicine found that a compound called FRAX486 stopped an out-of-control biological process in the brain (a so-called “pruning” process) that destroys essential connections of brain cells in schizophrenia.

"By using this compound to block excess pruning in adolescent mice, we also normalized the behavior deficit," said Dr. Sawa, Professor of Psychiatry and Behavioral Sciences. “Drugs aimed at treating a disease should be able to reverse an already existing defect as well as block future damage," and, he says, "this compound has the potential to do both."

The new study, funded in part by Dr. Sawa’s NARSAD Grant, was reported online on March 31st in the Proceedings of the National Academy of Sciences. The researchers report that the administration of FRAX486 stopped the excess pruning and resulted in the restoration of vital parts of neurons called spines, which help neurons communicate with one another.

To measure the impact on behavioral symptoms, the researchers tested the mice for their reaction to noises, to determine if there was a lessening impact of a startling noise if the mice first heard a weaker noise. This is a common phenomenon in schizophrenia: whereas healthy people will respond less to a startling noise after hearing a weaker one first, in schizophrenia, the first noise makes no impact on the reaction to the second one. The mice treated with FRAX486 in the study showed improvements in their reactions to the startling noise after heeding the warning from the first weaker noise.

Dr. Sawa cautions, however, that there is much work to be done before this compound can be confirmed as an effective treatment for schizophrenia in humans.

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