Compositions and methods for the treatment of carboxyhemoglobinemia
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsMark T. Gladwin, Jesus Tejero Bravo
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Abstract
Described herein is a new antidote for the rapid elimination of carbon monoxide from hemoglobin, including brain, heart, and red cell hemoglobin. The disclosed therapy involves the use of modified human globins, particularly neuroglobins modified at residue 64 and cytoglobins modified at residue 81, which bind carbon monoxide with extremely high affinity. The monomeric mutant globins are infused into blood, where they rapidly and irreversibly sequester carbon monoxide, and thus limit toxic effects of carbon monoxide on cellular respiration and oxygen transport and utilization.
Claims20
A method of treating carboxyhemoglobinemia in a subject, comprising:
- selecting a subject with carboxyhemoglobinemia;
- and
- administering to the subject a therapeutically effective amount of a recombinant globin molecule that binds carbon monoxide with high affinity, wherein the recombinant globin molecule comprises:
- a human recombinant neuroglobin with a H64Q, H64L, H64A or H64W mutation;
- or
- a human recombinant cytoglobin with a H81Q, H81A, H81L or H81W mutation, thereby treating carboxyhemoglobinemia in the subject.
A method of removing carbon monoxide from hemoglobin in blood or tissue, comprising contacting the blood or tissue with a recombinant globin molecule that binds carbon monoxide with high affinity, wherein the recombinant globin molecule comprises:
- a human recombinant neuroglobin with an H64Q, H64L, H64A or H64W mutation;
- or
- a human recombinant cytoglobin with an H81Q, H81A, H81L or H81W mutation,
- thereby removing carbon monoxide from hemoglobin in the blood or tissue.
A human recombinant globin molecule comprising:
- a human recombinant neuroglobin comprising a mutation at residue 64, and further comprising a C46G mutation, a C55S mutation and a C120S mutation;
- or
- a human recombinant cytoglobin comprising a mutation at residue 81, and further comprising a C38S mutation and a C83S mutation.
Dependencies are inferred from the claim text.