Use of caspase inhibitors as a therapeutic agent against radiation-induced injury
OwnerDaohong Zhou, Aimin Menginventors
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Abstract
The present invention provides methods for the treatment of radiation-induced injury by providing to a subject a caspase inhibitor. The caspase inhibitor may be provided before or after the radiation injury, and further may be provided in combination with a second caspase inhibitor, an anti-apoptotic molecule, a radioprotectant, a cytokine or a growth factor.
Claims46
A method of inhibiting apoptosis in a hematopoietic stem cell (HSC) comprising contacting said cell with a caspase inhibitor in an amount sufficient to inhibit apoptosis in said cell.
A method of inhibiting radiation-induced injury in a subject comprising administering to said subject a caspase inhibitor in an amount sufficient to inhibit radiation-induced injury.
A method of screening a caspase inhibitor for its ability to inhibit radiation-induced injury comprising:
- (a) providing a hematopoietic stem cell (HSC);
- (b) contacting said HSC with a dose of ionizing radiation sufficient to induce apoptosis in said HSC;
- (c) contacting said HSC with said caspase inhibitor;
- and
- (d) assessing one or more apoptotic characteristics in said HSC,
- wherein a reduction in the number or extent of apoptotic characteristics in said HSC, as compared to an HSC not treated with said caspase inhibitor, identifies said caspase inhibitor as an inhibitor of radiation-induced injury.
A composition comprising a radioprotectant and a second agent selected from the group consisting of an anti-apoptotic molecule (a p53 inhibitor or an anti-apoptotic protein, such as Bcl-XL, Bcl-2, c-IAP1, c-IAP2, and XIAP), a radioprotectant (amifostine, vitamin E, vitamin C, selenium, melatonin, 5-androstenediol, cucumin, α-phenyl-tert-butylnitrone, a flavinoid, or a nitroxide), a cytokine (IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7), or a growth factor (Flt3 ligand, c-Kit ligand, M-CSF, GM-CSF, G-CSF, VEGF, erythropoietin, leukemia inhibitory factor).
Dependencies are inferred from the claim text.