治療抵抗性統合失調症の克服に向けた結合組織成長因子CTGFの役割と脳内デリバリー

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  • Potential role of connective tissue growth factor in overcoming treatment-resistant schizophrenia

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<p>Schizophrenia affects more than 20 million people worldwide, and approximately one third of patients have a limited response to antipsychotic medication treatment and are assessed to have treatment-resistant schizophrenia. Clozapine is the only drug with proven efficacy in schizophrenia that does not respond to other antipsychotics. However, potentially serious side effects such as agranulocytosis have limited clozapine treatment. Using comprehensive combined gene expression analysis and proteomics analysis, we have identified connective tissue growth factor (CTGF), a modular secreted protein, involved in the ameliorative effects of clozapine on cognitive impairments. CTGF, also known as CCN2, is a 38 kDa, cysteine-rich, extracellular matrix protein. We have found that coadministering peptides and proteins with the cell-penetrating peptide L-penetratin intranasally significantly increased transport to the brain and enhanced pharmacological effects. We thus demonstrated that chronic administration of intranasal CTGF with L-penetratin improved cognitive impairments. Additionally, concomitant treatment with intranasal injection of the neutralizing antibody against CTGF and L-penetratin blocked the effects of clozapine. In this symposium, we would like to discuss about new treatment perspectives in treatment-resistant schizophrenia.</p>

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