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February 6, 2015

Screening and personalizing nootropic drugs and cognitive modulator regimens in silico. Front Syst Neurosci.

Written and published by Biogerontology Research Foundation staff in collaboration with University of Tennessee Health Science Center (Department of Genetics, Genomics, and Informatics), Insilico Medicine, Inc. and Pathway Pharmaceuticals Ltd.

Screening and personalizing nootropic drugs and cognitive modulator regimens in silico. Front Syst Neurosci. 2015 Feb 6;9:4.

Jellen LC(1), Aliper A(2), Buzdin A(3), Zhavoronkov A(4).

(1) Department of Genetics, Genomics, and Informatics, University of Tennessee Health Science Center Memphis, TN, USA.

(2) Aging Research, Insilico Medicine, Emerging Technology Center, Johns Hopkins University Eastern Baltimore, MD, USA.

(3) Personalized Medicine, Pathway Pharmaceuticals Ltd Wan Chai, Hong Kong.

(4) Aging Research, Insilico Medicine, Emerging Technology Center, Johns Hopkins University Eastern Baltimore, MD, USA ; Research, Biogerontology Research Foundation Truro, UK.

Abstract: The go-to cognitive enhancers of today are those that are widely available rather than optimal for the user, including drugs typically prescribed for treatment of ADHD (e.g., methylphenidate) and sleep disturbances such as narcolepsy (modafinil). While highly effective in their intended therapeutic role, performance gains in healthy populations are modest at best and profoundly inconsistent across subgroups and individuals. We propose a method for in silico screening of possible novel cognitive enhancers followed by high-throughput in vivo and in vitro validation. The proposed method uses gene expression data to evaluate the the collection of activated or suppressed signaling pathways in tissues or neurons of the cognitively enhanced brain. An algorithm maps expression data onto signaling pathways and quantifies their individual activation strength. The collective pathways and their activation form what we term the signaling pathway cloud, a biological fingerprint of cognitive enhancement (or any other condition of interest). Drugs can then be screened and ranked based on their ability to minimize, mimic, or exaggerate pathway activation or suppression within that cloud. Using this approach, one may predict the efficacy of many drugs that may enhance various aspects of cognition before costly preclinical studies and clinical trials are undertaken.

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