Investigating the mechanism of action of a new gold based therapeutic with re-myelinating properties

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Vandana Garikipati (Creator)
The University of North Carolina at Greensboro (UNCG )
Web Site:
Christopher Kepley

Abstract: The focus of this thesis is on in vitro studies of a new therapeutic gold nanocrystal CNM-Au8, manufactured under cGMP process using a patented electro-crystal-chemistry process by Clene Nanomedicine, Inc (, a clinical-stage biopharmaceutical company. A highly concentrated suspension of gold nanocrystals (CNM-Au8) has demonstrated significant effects on myelin preservation and/or remyelination in vitro and in vivo, proven safe in phase 1, and is under Phase 2 clinical trials as a new way to promote remyelination and repair damaged nerves. Herein, the mechanism of action and kinetics of cellular uptake of CNM-Au8 was examined in human oligodendrocytes. Gold nanocrystals were observed in mitochondria, Golgi, and lysosomes with peak uptake at approximately 96. A marked increase of intracellular gold nanocrystals was observed at the cell periphery at 168 hours after application. Protein microarray analyses of oligodendrocytes treated with CNM-Au8 for 10 minutes revealed upregulation of several signal transduction pathways including those involved in bioenergetics (MAPK14/ERK1,2) and myelin basic protein (MBP) production (ERK1-2/cAMP) which are both critical factors in myelin sheath function. CNM-Au8 upregulated MBP expression in oligodendrocyte was confirmed using immunohistochemistry. These results suggest the gold nanocrystals of CNM-Au8 penetrate oligodendrocyte cell membranes and reside temporarily within cells to stimulate energetic and anabolic pathways to myelin production. The potential of CNM-Au8 in regulating intracellular signals that influence the underlying repair mechanisms to preserve and/or enhance remyelination after CNS damage cannot be ruled out. [This abstract has been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]

Additional Information

Language: English
Date: 2019
Demyelination, Gold nanocrytals, Multiple Sclerosis, Myelination, Oligodendrocytes, Proteomics
Nanocrystals $x Therapeutic use
Multiple sclerosis

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