Erratum: Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance (2018 J. Neural Eng. 15 025002)

Q2 · ENGINEERING & TECHNOLOGY

Article

Author: Patrick Smith ; Nicholas P. Ziats ; Grace Protasiewicz ; Vishnupriya Srivastava ; John K. Hermann ; Kyle Kovach ; Steven Sidik ; Dawn Marie Taylor ; Stephen M. Selkirk ; Jeffrey B. Capadona ; Chun Wong ; Andrew Shoffstall ; Jingle Jiang ; Robert H Miller ; Arielle Soffer ; Jeremy Chang ; Evon Ereifej ; Madhumitha Ravikumar

[This corrects the article PMC5818286.].

01 Apr 2018·Journal of Neural EngineeringQ2 · ENGINEERING & TECHNOLOGY

Inhibition of the cluster of differentiation 14 innate immunity pathway with IAXO-101 improves chronic microelectrode performance

Q2 · ENGINEERING & TECHNOLOGY

Article

Author: Patrick Smith ; Nicholas P. Ziats ; Vishnupriya Srivastava ; Grace Protasiewicz ; John K. Hermann ; Andrew J. Shoffstall ; Steven Sidik ; Dawn Marie Taylor ; Stephen M. Selkirk ; Jeffrey B. Capadona ; Chun Wong ; Jingle Jiang ; Robert H Miller ; Kyle M. Kovach ; Arielle Soffer ; Jeremy Chang ; Madhumitha Ravikumar ; Evon S. Ereifej

OBJECTIVENeuroinflammatory mechanisms are hypothesized to contribute to intracortical microelectrode failures. The cluster of differentiation 14 (CD14) molecule is an innate immunity receptor involved in the recognition of pathogens and tissue damage to promote inflammation. The goal of the study was to investigate the effect of CD14 inhibition on intracortical microelectrode recording performance and tissue integration.APPROACHMice implanted with intracortical microelectrodes in the motor cortex underwent electrophysiological characterization for 16 weeks, followed by endpoint histology. Three conditions were examined: (1) wildtype control mice, (2) knockout mice lacking CD14, and (3) wildtype control mice administered a small molecule inhibitor to CD14 called IAXO-101.MAIN RESULTSThe CD14 knockout mice exhibited acute but not chronic improvements in intracortical microelectrode performance without significant differences in endpoint histology. Mice receiving IAXO-101 exhibited significant improvements in recording performance over the entire 16 week duration without significant differences in endpoint histology.SIGNIFICANCEFull removal of CD14 is beneficial at acute time ranges, but limited CD14 signaling is beneficial at chronic time ranges. Innate immunity receptor inhibition strategies have the potential to improve long-term intracortical microelectrode performance.

Scientific ReportsQ3 · CROSS-FIELD

TLR4-Mediated Placental Pathology and Pregnancy Outcome in Experimental Malaria

Q3 · CROSS-FIELD

ArticleOA

Author: Murillo, Oscar Javier ; Lima, Maria Regina D'Império ; Bandeira, Carla Letícia ; Bevilacqua, Estela ; Peixoto, Erika Paula Machado ; Wunderlich, Gerhard ; Lima, Flávia Afonso ; Marinho, Claudio Romero Farias ; Costa, Fabio Trindade Maranhão ; Epiphanio, Sabrina ; Alvarez, José Maria ; Sardinha, Luis Roberto ; Barboza, Renato ; Gonçalves, Lígia Antunes ; Reis, Aramys Silva ; Fotoran, Wesley Luzetti

AbstractMalaria-associate pregnancy has a significant impact on infant morbidity and mortality. The detrimental effects of malaria infection during pregnancy have been shown to correlate with immune activation in the placental tissue. Herein we sought to evaluate the effect of Toll-like receptors (TLRs) activation on placental malaria (PM) development by using the Plasmodium berghei NK65GFP infection model. We observed that activation of the innate immune system by parasites leads to PM due to local inflammation. We identified TLR4 activation as the main pathway involved in the inflammatory process in the placental tissue since the absence of functional TLR4 in mice leads to a decrease in the pro-inflammatory responses, which resulted in an improved pregnancy outcome. Additionally, a similar result was obtained when infected pregnant mice were treated with IAXO-101, a TLR4/CD14 blocker. Together, this study illustrates the importance of TLR4 signalling for the generation of the severe inflammatory response involved in PM pathogenesis. Therefore, our results implicate that TLR4 blockage could be a potential candidate for therapeutic interventions to reduce malaria-induced pathology both in the mother and the fetus.

100 Deals associated with IAXO-101

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Indication	Highest Phase	Country/Location	Organization	Date
Inflammation	Preclinical	GB	Innaxon Therapeutics	-

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