Compositions and methods of using chondroitinase ABCI mutants
AssigneeAcorda Therapeutics, Inc.
InventorsAnthony O. Caggiano, Andrea Vecchione, Jennifer Iaci
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Abstract
The present invention relates to protein and nucleic acid mutants of chondroitinase ABCI. Such chondroitinase ABCI mutant enzymes exhibit altered chondroitin lyase activity or increased resistance to inactivation from stressors including UV light or heat. Methods of using chondroitinase ABCI mutant enzymes are also provided.
Claims32
An isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
A method of treating a central nervous system injury comprising administering a therapeutically effective amount of an isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
A method of promoting neuronal outgrowth comprising administering a therapeutically effective amount of an isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
A method of facilitating diffusion of an agent in a central nervous system comprising:
- administering the agent to the central nervous system;
- and
- administering to the central nervous system an isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
A method of enhancing uptake of an agent in a central nervous system, comprising administering the agent and at least one enzyme capable of cleaving chondroitin sulfate proteoglycans, wherein the at least one enzyme comprises an isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
A method for inhibiting extravasation of cells from blood vessels comprising administering to a patient an enzyme that cleaves a chondroitin sulfate proteoglycan, wherein the enzyme comprises an isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
A method of treating inflammation in a patient comprising administering to the patient an enzyme that cleaves chondroitin sulfate proteoglycans, wherein the enzyme comprises an isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
A method of treating inflammation in a patient comprising:
- extracting cells circulating in the blood stream of the patient;
- subjecting the cells to an enzyme that cleaves chondroitin sulfate proteoglycan ex vivo to modify the cells;
- and
- administering the modified cells to the patient,
- wherein the enzyme comprises an isolated mutant chondroitinase ABCI enzyme comprising the amino acid sequence of SEQ ID NO:
- 5.
Dependencies are inferred from the claim text.