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. !
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. !