Experimental Cancer Drug FRAX486 'Reverses Schizophrenia in Mice'

An experimental cancer drug appears to be able to reverse schizophrenia in mice, researchers at Johns Hopkins Medicine have found.

The team say an experimental anticancer compound can reverse behaviours associated with schizophrenia in adolescent mice with the rodent version of the disease.

They also discovered some of the lost brain cell function was restored in mice being administered the cancer drug.

Published in the Proceedings of the National Academy of Sciences, the researchers discovered the compound - FRAX486 – appears to halt a pruning process in the schizophrenic brain in which vital neural connections are destroyed.

The drug is one of a class of compounds called PAK inhibitors which provide some protection from brain damage caused through inherited disease. There is also evidence to show the drug could be used to treat Alzheimer's, while previous studies have found the PAK protein can initiate cancer and cell growth, meaning inhibitors could be developed to fight cancers.

The team said they were able to restore disabled neurons in adolescent and young adult mice with schizophrenia through FRAX486.

Study leader Akira Sawa said: "By using this compound to block excess pruning in adolescent mice, we also normalised the behaviour deficit. That we could intervene in adolescence and still make a difference in restoring brain function in these mice is intriguing."

In their experiments, the researchers reduced the expression of a gene called Disrupted-in-Schizophrenia 1 (DISC1), which appears to regulate the fate of neurons involved in higher order functions like information processing.

The deficit in DISC1 caused deterioration of parts of the brain that help neurons to communicate with one another. It also means the regulation of another protein, Rac1, cannot be controlled. Excess Rac1 leads to excess PAK in mice.

By reducing the activity of PAK, the team was able to protect the mice against the effects of having too little DISC1.

It is not yet known if PAK is elevated in the brains of humans with schizophrenia, meaning further research is needed before the drug is considered for use in humans.

"Drugs aimed at treating a disease should be able to reverse an already existing defect as well as block future damage," Sawa said. "This compound has the potential to do both."