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Advances in toponomics drug discovery: Imaging cycler microscopy correctly predicts a therapy method of amyotrophic lateral sclerosis
Author(s) -
Schubert Walter
Publication year - 2015
Publication title -
cytometry part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.316
H-Index - 90
eISSN - 1552-4930
pISSN - 1552-4922
DOI - 10.1002/cyto.a.22671
Subject(s) - drug discovery , in vivo , fluorescence microscope , robustness (evolution) , fluorescence lifetime imaging microscopy , computational biology , molecular imaging , microbiology and biotechnology , preclinical imaging , biophysics , biology , chemistry , computer science , bioinformatics , biochemistry , physics , fluorescence , quantum mechanics , gene
An imaging cycler microscope (ICM) is a fully automated (epi)fluorescence microscope which overcomes the spectral resolution limit resulting in parameter‐ and dimension‐unlimited fluorescence imaging. This enables the spatial resolution of large molecular systems with their emergent topological properties (toponome) in morphologically intact cells and tissues displaying thousands of multi protein assemblies at a time. The resulting combinatorial geometry of these systems has been shown to be key for in‐vivo/in‐situ detection of lead proteins controlling protein network topology and (dys)function: If lead proteins are blocked or downregulated the corresponding disease protein network disassembles. Here, correct therapeutic predictions are exemplified for ALS. ICM drug target studies have discovered an 18‐dimensional cell surface molecular system in ALS‐PBMC with a lead drug target protein, whose therapeutic downregulation is now reported to show statistically significant effect with stop of disease progression in one third of the ALS patients. Together, this clinical and the earlier experimental validations of the ICM approach indicate that ICM readily discovers in vivo robustness nodes of disease with lead proteins controlling them. Breaking in vivo robustness nodes using drugs against their lead proteins is likely to overcome current high drug attrition rates. © 2015 The Author. Published by Wiley Periodicals, Inc, on behalf of ISAC.