FK866 treatment in DSS-induced colitis mouse model

Validation Score: 0.900 Price: $0.50 Inflammatory bowel disease (colitis) DSS-induced colitis mice Status: proposed

What This Experiment Tests

Validation experiment designed to validate causal mechanisms targeting NAMPT in DSS-induced colitis mice. Primary outcome: Colitis severity and inflammatory markers

Description

Investigation of the therapeutic effects of FK866, a NAMPT inhibitor, in a dextran sulfate sodium (DSS)-induced colitis mouse model. The study examined how FK866 treatment affects inflammatory markers, NAD metabolism, and disease severity in acute intestinal inflammation. The experiment demonstrated that FK866 ameliorated colitis symptoms by reducing mucosal NAD levels, inhibiting NAD-dependent enzymes (PARP1, Sirt6, CD38), decreasing NF-κB activation, and reducing inflammatory cell infiltration including monocytes, macrophages, and activated T cells. The mechanism was linked to altered macrophage polarization with reduced pro-inflammatory markers (CD86, CD38, MHC-II, IL-6) and increased anti-inflammatory markers (CD206, Egr2, IL-10).

TARGET GENE
MODEL SYSTEM
DSS-induced colitis mice
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
NAD salvage pathway, NF-κB signaling
SOURCE
extracted_from_pmid_28877980
PRIMARY OUTCOME
Colitis severity and inflammatory markers

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.900 composite

📖 Wiki Pages

NAMPT GenegeneNAMPT ProteinproteinNAD+ Boosters for NeurodegenerationtherapeuticNAD+ Precursors for NeurodegenerationtherapeuticCD38 Molecule (CD38)genePARP1 GenegeneNAD+ Precursors (NMN/NR) for Parkinson's DiseasetherapeuticCD38 Inhibition + NAD+ Precursor Synergy for NeuroideaPARP1 Inhibition for Parthanatos Prevention in NeuideaNAD+ Precursor Therapy for Neurodegenerative DiseatherapeuticNAD+ Bioenergetics Investment SynthesismechanismNAD+ Metabolism in NeurodegenerationmechanismNAD+ Metabolism Pathway in NeurodegenerationmechanismNAD Signaling in Neurodegenerationmechanismnad-augmentation-therapy-early-adgeneral

Protocol

DSS administration to induce colitis followed by FK866 treatment with assessment of mucosal NAD levels, enzyme activities, inflammatory cell infiltration, and cytokine production

Expected Outcomes

FK866 would reduce inflammation by depleting NAD and inhibiting inflammatory pathways

Success Criteria

Reduced colitis severity, decreased inflammatory markers, and altered immune cell populations

Related Hypotheses (3)

TREM2 R47H Variant-Driven Metabolic Dysfunction as the Primary Trigger for Failed DAM Transition0.862
Metabolic NAD+ Salvage Pathway Enhancement Through NAMPT Overexpression0.745
NAD+ Salvage Pathway Optimization0.455

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