Clozapine Sensors for Improving Therapeutic Treatments of Schizophrenia

描述（由申请人提供）：精神分裂症是一种慢性和使人衰弱的脑部疾病，在特定年份影响约1.1%的美国18岁及以上人口，占美国所有疾病负担的5%。据估计，20%至60%的患者患有难治性精神分裂症。尽管存在毒副作用的风险，氯氮平仍然是治疗难治性精神分裂症唯一有效的抗精神病药物。氯氮平的毒性很难控制，部分原因是氯氮平代谢的高度人际变异性和不可预测性。因此，为了增加氯氮平的使用，改善氯氮平的治疗效果，防止潜在的危及生命的副作用，通过调整剂量来监测血浆药物浓度的治疗药物被提倡。利用Lucerna创始人开发的专利传感器开发技术，我们将开发小型便携式设备，用于快速、无创、廉价地检测唾液中的氯氮平及其药理活性代谢物去氯氮平水平。该装置将允许氯氮平剂量被仔细滴度，以确保患者维持治疗和安全的氯氮平水平。这个第一阶段的SBIR应用描述了开发、表征和优化氯氮平传感纳米器件的灵敏度、选择性和动力学的概念验证实验。第一阶段的成功完成将支持我们的核心假设，并将导致第二阶段的实验，包括将氯氮平传感纳米装置调整到便携式读出平台，并根据FDA标准评估当前氯氮平检测和验证方法的原型传感器装置。由此产生的产品在治疗药物监测市场的关键领域（如家庭、精神科医生办公室和门诊护理设施）具有很高的用户接受潜力。！

DESCRIPTION (provided by applicant): Schizophrenia is a chronic and debilitating brain disorder that affects about 1.1 percent of the US population age 18 and older in a given year and account for 5% of all disease burden in the US. It is estimated that 20% to 60% of patients have treatment-resistant schizophrenia. Clozapine remains the only effective antipsychotic for treatment-resistant schizophrenia despite the risks of toxic side effects. The toxicities of clozapine are difficult to manage, in part, because of the high interpersonal variability and unpredictability in clozapine metabolism. Thus, therapeutic drug monitoring of plasma drug concentrations through dose adjustments has been advocated in order to increase the use of clozapine, improve clozapine treatment outcome, and prevent potential life- threatening side effects. Using a patented sensor development technology developed by Lucerna founders, we will develop small portable devices for rapid, non-invasive, and inexpensive detection of clozapine and its pharmacologically active metabolite, norclozapine, levels in saliva. This device will allow clozapine dosage to be carefully titered to ensure that patients maintain a therapeutic and safe clozapine level. This phase I SBIR application describes proof-of-concept experiments for developing, characterizing, and optimizing the sensitivity, selectivity, and kinetics of a clozapine- sensing nanodevice. Successful completion of phase I will support our core hypothesis and leads to Phase II experiments that involve adapting the clozapine-sensing nanodevice to a portable readout platform and assessing the prototype sensor device against current methods of clozapine detection and validation according to FDA standards. The resulting product has a high potential for user acceptance in key segments in the therapeutic drug monitoring market such as homes, psychiatrist's offices, and outpatient care facilities. ! PUBLIC HEALTH RELEVANCE: It is estimated that about one million Americans have treatment-resistant schizophrenia, for which clozapine is the most effective antipsychotic drug. However, high interpersonal variability and unpredictability in clozapine metabolism, as well as toxic side effects make doctors reluctant to prescribe this otherwise remarkably effective medication. We will develop a sensitive and simple clozapine-sensing nanodevice that will facilitate routine therapeutic drug monitoring, enabling optimized dosing and efficacy for this important antipsychotic drug. !