Genetika+: precision medicine solutions for mental health

Genetika+ is a fast-growing women-led company founded in 2018 in Israel with the mission of improving patient outcomes in mental health, with the first indication being major depression. Realizing that each patient is unique, Genetika+ has developed a truly personalized medical tool, a simple blood test that predicts which medication an individual will respond to and thus better treat depression and help physicians find the shortest route to healing for their patients. Dr Talia Cohen Solal, the CEO and founder of Genetika+, is an alumnus of Oxford University, University College London and Columbia University, and is bringing her expertise from the bench to this technology, together with her cofounder Dr Daphna Laifenfeld, previously the head of personalized medicine at Teva Pharmaceuticals. Together they lead a team of 17 scientists and professionals dedicated to providing a cutting-edge approach for solving one of the most widespread diseases.

The challenge

Major depressive disorder (MDD) is the largest contributor to the reduced of health-related quality of life [1], with up to 14 life years lost per patient. It is an extremely heterogeneous disease with varied clinical manifestations and treatment responsiveness stemming from complex genetic and environmental factors unique to each individual’s phenotypes [2]. Depression affects 300 million people globally and was the second leading cause of disability by 2020 [3], contributing to 917 accumulated years lost per 100,000 people [4]. Nevertheless, three out of four people suffering from depression do not receive adequate treatment [5]. The lack of information about the unique neuronal properties underlying each patient’s depressive disease has historically resulted in a prescription by the physician from a very broad drug selection, based only on patient clinical observation and a brief interview. As a result, 63% of patients try multiple medications, and a third of patients will not respond even after two rounds of drug testing [6]. With more than 70 antidepressants to choose from and with each antidepressant requiring weeks before response levels can be determined, the patient loses months to testing until the right treatment is found for them and, in the process, suffers the devastating effects of depression and potential side effects of disease comorbidities, job loss and social impacts.

The need: a truly personalized treatment

Clinical studies are typically conducted on broad populations, focusing on general patterns for common physiological mechanisms. However, individuals can exhibit different responses to the same medication. In extreme cases, an efficient drug for one patient causes life-threatening toxicity in another [7,8], or simply has no effect. Individual response to any medication depends partly on patient-specific drug metabolism, whereas antidepressant efficacy depends primarily on its effect on the patient’s brain. Therefore, although genetic variation of the enzymes responsible for drug metabolism influences drug response, the unique neuronal network of each patient will ultimately determine whether an antidepressant treatment will result in a clinical response. Consequently, a combination of both the genetic and the neurological background of the patient needs to be considered for an individualized and effective treatment. There is a significant need for an evidence-based personalized treatment approach that takes the target organ into to account and is able to reduce trial-and-error drug prescription.

The NeuroKaire solution

To address the needs of patients, physicians, and health care systems, Genetika+ provides a personalized treatment solution. NeuroKaire combines, on top of traditional pharmacogenetics, innovative stem cell technology, neurobiology, high-throughput screening and machine learning to test a broad spectrum of antidepressants, simulating drug effects in a patient-specific, ‘brain-in-a-dish’ model. A personalized drug recommendation is then delivered to the physician in a tailored report, supporting a doctor’s decision to prescribe the optimal treatment for the patient.

How does NeuroKaire work?

In a three-step procedure, NeuroKaire creates a personalized treatment recommendation using simple blood collection (Figure 1).

Our first product, NeuroKaire, focuses specifically on major depressive disorder treatment prediction, but our brain-in-a-dish model and predictive platform is applicable to treatment prediction for multiple psychiatric disorders, including bipolar disorder, attention-deficit/hyperactivity disorder and schizophrenia, in the future, in addition to current use for drug discovery, screening and validation.

Uniqueness of NeuroKaire: neuronal simulation

NeuroKaire innovates by using scaled simulation of neuronal responses

For the first time in antidepressant response prediction assays, we are using stem cell technology to convert patient blood cells into neurons to test the drug response on the patient’s target organ. NeuroKaire assesses a dynamic neuronal response to the drug at a functional level, underlying the patient clinical response to the drug. In vitro neuronal readouts have never been used as decision-support tools for depression personalized treatment.

NeuroKaire innovates using a novel proprietary algorithm for treatment prediction in depression

NeuroKaire uses artificial intelligence and machine learning to combine patient history, genetic background and neurobiology, side effect profiling and comorbidity analysis. The algorithms generated based on these data boost the power of our predictive platform. This allows for an accurate response prediction leading to technological advances in the field.