Method for identifying novel treatments of inflammatory disease in the gut
OwnerPaul Goldsmith, Angeleen Fleminginventors
Life of this patent
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Abstract
Model fish and use thereof for screening for the presence of gut inflammatory disease, especially in zebrafish. Induction of the disease state and visualization of the gastrointestinal tract in living zebrafish. Visualization of the inflammatory state in vivo facilitates screening for compounds that can be used in treatment of inflammatory disease of the gut or genetic mutations that rescue or suppress the disease phenotype.
Claims29
A fish model for gut inflammatory disease, wherein a pro-inflammatory agent trinitrobenzene sulfonic acid (TNBS) or dextran sulphate sodium (DSS) is administered to medium containing embryonic fish to induce the disease state in the fish gut.
A fish model for screening for gut function and/or disease phenotype, wherein a non-toxic, non-absorbed fluorescent dye is administered to medium containing embryonic fish that are optically clear to allow visualization of the fish gut following swallowing of the dye by the fish.
A method of generating a fish model for gut inflammatory disease, the method comprising administering a pro-inflammatory agent trinitrobenzene sulfonic acid (TNBS) or dextran sulphate sodium (DSS) to medium containing embryonic fish to induce the disease state in the fish gut.
A method of generating a fish model for screening for gut function and/or disease phenotype, the method comprising administering a non-toxic, non-absorbed fluorescent dye to medium containing embryonic fish that are optically clear to allow visualization of the fish gut following swallowing of the dye by the fish.
A method for assessing nausea, vomiting and/or an anti-emetic, an emesis inducing compound, the method comprising:
- administering to a fish that is optically clear a non-toxic, non-absorbed fluorescent or otherwise labeled compound which is ingested,
- administering to the fish the emesis inducing compound and/or inducing nausea through pipetting or rapid movement,
- assessing movement of the labeled compound through the gut of the fish, or its re-emergence from the mouth of the fish.
A method for assessing gut motility, IBS, diarrhea or constipation, the method comprising:
- administering to a fish a fluorescent- or otherwise-labeled compound which is ingested or directly visualizing the gut,
- optionally administering to the fish a motility modifying compound,
- assessing movement of the labeled compound through the gut, or movements of the gut itself, or emergence of the labeled compounds or of feces from the anus, and/or assessing quantity and quality of the feces.
A method for assessing stem cell activity, the method comprising:
- visualizing cell turnover and differentiation in a fish gut through:
- direct visualization of gut architecture through in vivo assessment or histological analysis, and/or BRDU labeling, or other labeling of mitotic activity,
- in the normal state, or following administration of a chemotoxin, cytotoxin or radiotherapy.
A method for assessing the effects of cancer therapies, the method comprising:
- visualizing cell turnover and differentiation in a fish gut through:
- direct visualization of gut architecture through in viva assessment or histological analysis, and/or BRDU labeling, or other labeling of mitotic activity
- in the normal state, or following administration of a chemotoxin, cytotoxin or radiotherapy.
A fish model for gut damage, wherein a chemotoxic agent sudan black in ethylene glycol or a cytotoxic agent is administered to medium containing embryonic fish to induce the disease state in the fish gut.
A method of generating a fish model for gut damage, the method comprising administering a chemotoxic agent sudan black in ethylene glycol or a cytotoxic agent to medium containing embryonic fish to induce damage in the fish gut.
Dependencies are inferred from the claim text.