Med Hypotheses. 2004;62(4):542-5. 

Intrathecal therapy with trastuzumab may be beneficial in cases of refractory schizophrenia.
Sastry PS, Sita Ratna W.

Jaslok Hospital and Research Centre, 15, D G Deshmukh Road (Pedder Road), Mumbai 400 026, Maharashtra, India. psrksastry2000@yahoo.com

Refractory schizophrenia has limited therapeutic options. Schizophrenia can be considered to be a disease of abnormal synaptic plasticity. Neuregulin is a member of the epithelial growth factor family, which induces growth and differentiation of epithelial, glial and muscle cells in culture. Neuregulin has been documented to be important in synaptic plasticity. The important role of neuregulin in synaptic plasticity as well as its developmental role have increasingly been documented recently. The actions of neuregulin are mediated through ERB receptors. Neuregulin can bind directly to erbB3 and erbB4 receptors and receptor heterodimerization allows neuregulin dependent activation of erbB2. The role of Erb 2 could make it possible to use the monoclonal antibody against it for improving the synaptic plasticity through the action on neuregulin. The use of trastuzumab (Her2 antibody) as targeted therapy is well documented in metastatic carcinoma of breast. Also intra-thecal administration of trastuzumab has been reported to be safe in carcinomatous meningitis. Here it is being hypothesized that intra-thecal administration of trastuzumab would improve synaptic plasticity there by making refractory schizophrenia amenable to treatment.

译文：
难治性精神分裂症极大的限制了治疗的选择。精神分裂症可以被考虑为一种突触可塑性出现异常的疾病。Neuregulin是表皮生长因子家族的一员，它可以诱导培养的上皮细胞、胶质细胞和肌肉细胞的生长和分化，并有文献报道在突触可塑性过程中具有重要作用。近来，Neuregulin在突触可塑性和发育中的作用屡有报道。Neuregulin的作用是通过ERB受体而发挥的。Neuregulin直接与erbB3和erbB4这两种受体相结合，并且通过这两种受体与erbB2受体异二聚化而激活erbB2受体。erbB2受体的单克隆抗体trastuzumab可以模拟Neuregulin的作用而提高突触可塑性。文献中详细描述了trastuzumab在乳腺转移癌的靶位定向治疗的使用。同时有报道认为鞘内注射trastuzumab治疗癌性脑膜炎是安全的。因此本文提出假说认为：鞘内注射trastuzumab会提高突触可塑性，进而使难治性精神分裂症易于治疗。

转自  zhangdi