The Historeceptomics Platform Revealed the Cause of a Drug's Undesireable Side Effect– and Pointed to a Surprising Solution

​In 2015, GeneCentrix was awarded an NIH Lab to Marketplace SBIR grant and an NIH Early Stage Development of Technologies in Biomedical Computing, Informatics, and Big Data Science SBIR grant in 2017. 

 

We validated our method by determining the mechanism of action of clozapine, an atypical antipsychotic. The results were published in Nature Translational Psychiatry (see below). 

 

After running clozapine through our novel informatics algorithm for predicting drugs' adverse effects, we discovered a number of data points associated with psychosis, including serotonin receptors 5HT-2A in the prefrontal cortex and 5HT-2C in the caudate nucleus.

 

Interestingly, one of the high-ranking data points was not associated with known mechanisms of psychosis: Clozapine had strong activity with the histamine H1 receptor in the superior cervical ganglion (SCG). The SCG innervates the salivary glands in humans, which explains the common and distressing side effect of clozapine: hypersalivation.

 

This result is the only study to date that identifies histamine H1 in the SCG as being responsible for hypersalivation. Thus, our tool can not only explain and predict adverse effects of your drug candidates, but can also offer you mitigating solutions – such as the use of an antihistamine to reduce the symptoms of hypersalivation.

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