A recent study at Nagoya University in Japan found that a drug called fasudil effectively improved schizophrenia symptoms and brain changes in mice. Researchers looked at mice with specific gene mutations on the Arhgap10 gene. The mutation is believed to be associated with schizophrenia. The mice with these mutations exhibited key signs and symptoms of schizophrenia.
“Previous to this study, a certain gene mutation was found to occur in higher rates of people with schizophrenia than in people who don’t have that condition. In addition, it was found that in mice that had this mutation experimentally induced, the mutation resulted in increased activity of a certain enzyme, Rho-kinase.”, says Dr. David Feifel, psychiatrist and neuroscientist, who are one of the spectators to the study.
Testing of Fasudil
Researchers theorized that inhibiting the enzyme, Rho-kinase would result in a reduction of schizophrenia manifestation. And so they gave the drug fasudil to mice to test this hypothesis.
Fasudil is a drug that functions as a brain permeable Rho-kinase inhibitor. It’s effects are investigated via altered spine density in the medial prefrontal cortex (mPFC) and on methamphetamine-induced cognitive impairment in a touchscreen‑based visual discrimination task in Arhgap10 S490P/NHEJ mice.
Results of the study showed significant improvements in two key areas:
- Mice exhibited an improved spin density of a specific brain area that was previously reduced.
- Mice showed improvement in cognitive functions that were previously impaired.
These findings indicate that rho-kinase activity plays a key role in schizophrenia and that inhibiting it may lead to the improvement of the said condition.
“The [researchers] gave the mice with the genetic mutation a drug which reduces Rho-kinase and found, that indeed, the mice given the drug had less of the brain and cognitive abnormalities than similar mice injected with a neutral substance indicating that the increase in Rho-Kinase activity was responsible for the schizophrenia-like brain and cognition abnormalities,” Dr. Feifel explained.
Study Limitations
Despite significant findings, the researchers acknowledge the many limitations of the study including the fact that the study done in mice. Further research is necessary to understand how the information would apply to humans. Research also noted the need to understand the underlying mechanisms of fasudil and what molecules it specifically impacts. Fasudil may also affect other enzymes and that these reactions may have contributed to the results.
“Developing an actual treatment based on this study is, however, still a long way off because this study only demonstrated effectiveness in a mouse model of schizophrenia. Animal models of schizophrenia are highly imperfect representations of schizophrenia, and often treatments that work in animal models do not work in humans with schizophrenia,” Dr. Feifel noted.
What this means for the treatment of Schizophrenia
Regardless, the study is a large step toward the advancement of understanding schizophrenia and the possibility of developing another treatment option for it.
“This study may offer hope in the discovery of a biological mechanism involved in the cognitive symptoms of schizophrenia.”, says Dr. John Cotonne, a licensed psychologist specializing in schizophrenia who is also a spectator of the said study.
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