Surfactant protein D for the prevention and diagnosis of pulmonary emphysema
AssigneeChildren's Hospital Medical Center
InventorJeffrey A. Whitsett M.D.
Life of this patent
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Abstract
Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. The SP-D gene was targeted by homologous recombination in embryonic stem cells that were used to produce SP-D (−/−) mice. The SP-D (−/−) deficiency caused inflammation, increased oxidant production by isolated alveolar macrophages, abnormal surfactant structure and levels, and decreased SP-A expression. Therefore, disclosed is the SP-D (−/−) mouse as an excellent model for emphysema. Also included are models for testing emphysema therapies in the mouse model, methods for using SP-D protein or DNA as a treatment for emphysema and pulmonary infections, and diagnosis.
Claims28
A non-human mammal having an SP-D (−/−) null phenotype.
A method for the prevention and treatment of pulmonary disease comprising:
- introducing mammalian SP-D protein, or vectors expressing the mammalian SP-D protein into a human in an amount effective to reduce the symptoms of or prevent pulmonary disease.
A pharmaceutical composition effective in treating pulmonary disease in mammals comprising:
- SP-D protein in admixture with a pharmaceutically acceptable excipient.
A biologically active agent for treating pulmonary disease in mammals comprising an agent that up-regulates expression of SP-D.
A biologically active agent for treating pulmonary disease in mammals comprising a vector expressing SP-D.
A biologically active agent for treating pulmonary disease in mammals comprising an agent that interacts with the SP-D protein.
A method for diagnosing susceptibility to pulmonary disease comprising the steps of:
- identifying a mutation in the SP-D gene which results in deficient SP-D identifying said mutation in a test subject.
A method of purifying SP-D antibodies comprising:
- reaction of SP-D antibodies with a solid phase lung homogenate from any mouse with does not produce SP-D protein.
A method for the prevention and treatment of pulmonary disease comprising:
- introducing mammalian SP-D protein, or vectors expressing the mammalian SP-D protein into a human in an amount effective to reduce the symptoms of or prevent pulmonary disease, wherein the pulmonary disease is selected from the group consisting of:
- reactive oxygen-mediated disease, chemically induced lung injury, injury due to oxygen radicals, injury due to ozone, injury due to chemotherapeutic agents, inflammatory and infectious diseases, reperfusion injury, drowning, transplantation, and rejection.
A method for the prevention and treatment of viral disease comprising:
- introducing mammalian SP-D protein, or vectors expressing the mammalian SP-D protein into a human in an amount effective to reduce the number of viruses or symptoms of the viral disease.
A method of inhibition of metalloproteinase activity and reactive oxygen species in the lungs, comprising, administering SP-D to the lungs in an amount effective to inhibit metalloproteinase activity and reactive oxygen species.
Dependencies are inferred from the claim text.