Ben-Gurion Researchers Develop Novel Method for Personalizing Clozapine Dose

Researchers at Ben-Gurion University of the Negev (BGU) have developed a novel method for accurately monitoring blood levels of the antipsychotic drug, clozapine, using a blood drop from a finger prick. The method, developed by Dr. Hadar Ben-Yoav, Department of Biomedical Engineering and Ilse Katz Institute for Nanoscale Science and Technology, BGU, is based on an electrochemical microsensor which enables, for the first time, clozapine detection in one drop of finger-pricked whole blood samples of schizophrenia patients without using any pretreatment steps.

Clozapine is considered the most effective antipsychotic medication for schizophrenia and the only antipsychotic currently approved for treatment-resistant schizophrenia but is also associated with harsh side effect. Both its efficacy and its side effects are strongly correlated with blood concentration levels, which can differ up to 20-fold between individuals prescribed identical doses, and can be greatly affected by age, gender, drug interactions and other parameters.

Despite the importance of monitoring clozapine blood levels, its current monitoring scheme is burdensome and involves frequent invasive blood draws, leading to sub-optimal treatment efficacy due to the poor ability to titrate its dose for maximal therapeutic benefit while minimizing side effects. As a result, clozapine is still one of the most underutilized evidence-based treatments in the field of mental health.

Dr. Ben-Yoav's team has invented a miniaturized microelectrode sensor that is able to accurately and immediately detect clozapine levels in a microliter-sample of whole blood such as obtained by a finger prick. A recent study carried out in collaboration with Prof. Deanna L. Kelly, Maryland Psychiatric Research Center (MPRC), University of Maryland, School of Medicine, showed good correlation between clozapine blood concentrations measured by the device compared to standard laboratory blood tests in schizophrenia patients.

"We were excited to see the promising initial results of our novel device, that can supply people with schizophrenia and their caretakers with instantaneous, accurate results of their blood clozapine levels. Clozapine plasma levels are helpful in improving response rates and minimizing unnecessary side effects. Our device can be the basis of rapid, accurate point-of-care monitoring of patients that will enable personalized medicine through close monitoring and adjustment of the dose of this important drug," Dr. Ben-Yoav, said.

"We hope that this innovative invention will help increase patient compliance and facilitate the use of clozapine for people living with schizophrenia," said Josh Peleg, CEO of BGN Technologies. "The medical research field is investing considerable efforts in simplifying and miniaturizing various blood tests, enabling patients to receive medical results immediately and at home, and the device being developed by the team of Dr. Ben-Yoav is an important contribution to this trend. Importantly, the technology underlying this novel clozapine sensor can be used as a platform for the detection of additional substances. After filing for patent protection, BGN Technologies is currently seeking a strategic partner for further developing and commercializing this device."

The novel sensor can be used as a platform for detecting other redox (reducing-oxidizing) chemicals in small quantities of untreated, whole blood samples. Redox molecules are involved in multiple significant chemical reactions, such as synthesis of various substances, biochemical processes in living organisms, diagnostics and medical procedures. Redox agents can be monitored by specific electrodes, but currently available methods of detection require pretreatment of the blood sample in order to separate the desired molecules from other, interfering substances. The sensor developed by Dr. Ben-Yoav's team can detect minute quantities of various redox molecules in untreated blood samples, thus paving the way for developing miniaturized, point-of-care devices that will be able to monitor various targets.