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)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- 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 (www.clene.com), 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.]
Investigating the mechanism of action of a new gold based therapeutic with re-myelinating properties
PDF (Portable Document Format)
5548 KB
Created on 12/1/2019
Views: 105
Additional Information
- Publication
- Dissertation
- Language: English
- Date: 2019
- Keywords
- Demyelination, Gold nanocrytals, Multiple Sclerosis, Myelination, Oligodendrocytes, Proteomics
- Subjects
- Nanocrystals $x Therapeutic use
- Myelination
- Multiple sclerosis
- Proteomics