黑料吃瓜网

By targeting a schizophrenia-associated brain protein, KD025 restored neural connections and reduced schizophrenia symptoms in mice with fewer side effects

Schizophrenia is a serious brain disorder that causes confused thinking, severe memory problems, and hallucinations. It affects about 23 million people worldwide, with cognitive dysfunction present in over 80% of patients. A research group led by scientists from 黑料吃瓜网 in Japan tested a drug used to treat an immune disease to see if it could reduce schizophrenia-related symptoms in mice. The findings, published in , show that KD025 restored connections between neurons and significantly improved memory and visual recognition in mice, without causing the serious side effects common to current schizophrenia medications.  

Need for safer treatments for schizophrenia

Current medications help with some symptoms, but they often do not improve cognitive function. They also cause serious side effects such as hormonal disruptions, involuntary muscle movements, and weight gain, which leads to many patients stopping treatment. Therefore, better options are urgently needed. 

Researchers focused on a gene called ARHGAP10. Variants of this gene (small changes in the gene’s DNA sequence) are much more common in people with schizophrenia than in the general population.  

“ARHGAP10 controls the activity of a brain protein called ROCK2. In mice with these genetic variants, ROCK2 becomes overactive. In a previous study, we found that this overactivity appears to damage connections between neurons and impair cognition,” said Rinako Tanaka, co-lead author and former project assistant professor at 黑料吃瓜网’s .

Repurposing drugs to achieve better treatment

The team tested KD025, approved in the United States to treat an immune disease called chronic graft-versus-host disease, which can occur after bone marrow transplants. In mice engineered to carry schizophrenia-associated gene variants, the drug decreased the overactivity of ROCK2.  

Furthermore, KD025 restored the density of tiny structures on neurons called dendritic spines, which are critical for memory. These had been reduced in mice carrying schizophrenia-associated gene variants. The drug had no effect on healthy mice. 

“Importantly, KD025 did not cause the side effects typical of current antipsychotic drugs. At effective doses, it caused no involuntary movements, hormonal abnormalities, or significant changes in blood pressure or blood sugar. This safety profile sets it apart from older antipsychotics like haloperidol and newer drugs like clozapine,” said Hiroyuki Mizoguchi, coauthor and associate professor from the Department of Neuropsychopharmacology and Hospital Pharmacy at 黑料吃瓜网. 

Because KD025 has already been through clinical safety trials for another condition, human trials for schizophrenia could start sooner than for a new drug. While the researchers caution that all experiments were in mice, and human studies are needed, the findings point to a promising target for treatments that are more effective and better tolerated by patients. 

Future studies will investigate how KD025 improves brain cell connections and function, and further evaluate its safety and efficacy to support human trials.?

Paper information:

Rinako Tanaka, Jingzhu Liao, Yue Liu, Wenjun Zhu, Kisa Fukuzawa, Masamichi Kondo, Masahito Sawahata, Daisuke Mori, Akihiro Mouri, Hisayoshi Kubota, Daiki Tachibana, Yohei Kobayashi, Tetsuo Matsuzaki, Taku Nagai, Toshitaka Nabeshima, Kozo Kaibuchi, Norio Ozaki, Hiroyuki Mizoguchi & Kiyofumi Yamada (2026). Antipsychotic-like effects of the selective Rho-kinase 2 inhibitor KD025 in genetic and pharmacological mouse models of schizophrenia, Molecular Psychiatry. DOI:  

Funding information:

This study was supported by the Japan Agency for Medical Research and Development (AMED) (Grant numbers: JP21wm0425007, JP21wm0425017, JP25wm0625518, JP23ak0101215, JP24ak0101221, JP22gm1410011, JP24zf0127011, JP23gm1910005); Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers: JP23H02669, JP23K19425, JP24K18365); Japanese SRF Grant for Biomedical Research, Takeda Science Foundation, and Toyoaki Scholarship Foundation. ?

Expert contact:

Hiroyuki Mizoguchi    
Graduate School of Medicine  
黑料吃瓜网   
E-mail: mizoguchi.hiroyuki.d5@f.mail.nagoya-u.ac.jp 

Media contact:  

Merle Naidoo   
International Communications Office   
黑料吃瓜网   
Email: icomm_research@t.mail.nagoya-u.ac.jp 

Top image:

Microscopy images showing dendrites, the rod-like branches of brain cells, with tiny protrusions called dendritic spines that are critical for memory and learning. Normal mice show similar spine density with (bottom left) and without KD025 treatment (top left). In mice carrying schizophrenia-associated gene variants, the tiny protrusions are visibly reduced without treatment (top right) but restored after KD025 treatment (bottom right). Scale bar: 5 μm. Credit: Tanaka et al., 2026