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Mind matters

Ken Kesey captured what is so frustrating about both schizophrenia and the primitive mental health system that is charged with treating it. The disease is characterized most visibly by “psychosis,” which is itself poorly defined, but generally means a break with reality, like hallucinations. But both in psychosis and in the other variable constellations of signs and symptoms, there is a lot of overlap with other treatable conditions. For example, a bad acid trip often looks exactly like schizophrenia, and even just getting bit manic about your favorite baseball team could raise some eyebrows outside the stadium.

That's what has made progress in drug development for schizophrenia so difficult. Not only is the disease poorly defined, but we need to map it to specific assays, animals and molecules used in drug development.

To this end, some time ago, GeneCentrix’ founding scientists applied our core technology–historeceptomics–to clozapine to shed some light on the mystery. We found that what clozapine has in common with its more pedestrian predecessors is the same target-tissue ensembles upon which LSD acts. Thus, mostly what the entire class of drugs do is alter psychosis. Not surprisingly, the main animal model of schizophrenia drug development is a psychosis model. Also not surprising, no drugs for the other symptoms of schizophrenia, e.g. flat affect (a negative symptom) and cognitive decline, have been developed. Clozapine at least seems to hint at cognitive improvement and has those mood effects. Indeed, historeceptomics revealed the drug targets and the region of the brain in which they act that might be responsible for these effects, opening new hypotheses in schizophrenia drug development.

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