Methods of treating or preventing pruritis by blocking natriuretic polypeptide b
Inventors
Hoon, Mark A. • MISHRA, Santosh K.
Assignees
US Department of Health and Human Services
Publication Number
US-10583173-B2
Publication Date
2020-03-10
Expiration Date
2034-12-04
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Abstract
Disclosed is a method of treating, reducing, or preventing pruritis in a mammal, the method comprising administering at least one natriuretic polypeptide b (Nppb) blocking agent to a mammal in an amount effective to treat or prevent pruritis in the mammal. An in vitro method of identifying a compound that inhibits Nppb activity is also disclosed.
Core Innovation
Itch, also known as pruritis, is an unpleasant skin sensation that can lead to a chronic condition significantly reducing quality of life. Current treatments for pruritis are inadequate, particularly for chronic forms caused by various conditions such as psoriasis, atopic dermatitis, renal failure, liver disease, and some cancers. There is a need for improved compositions and methods for treating pruritis.
The invention provides a method of treating, reducing, or preventing pruritis in a mammal by administering at least one natriuretic polypeptide b (Nppb) blocking agent in an effective amount. Nppb is required for pruriception, and blocking its activity treats pruritis. The Nppb blocking agent can be any agent that inhibits or reduces Nppb biological activity, including antibodies, antisense nucleic acids, chemical inhibitors, and receptor/ligand fusion proteins, while excluding neurotoxic agents such as Nppb-saporin conjugates.
An in vitro method is also provided for identifying compounds that inhibit Nppb activity by measuring reporter gene expression in cells expressing the Nppb receptor and a constitutive reporter gene controlled by cyclic AMP. A reduction in reporter gene expression upon treatment with a test agent and Nppb indicates inhibition of Nppb activity.
Claims Coverage
The patent includes one independent claim that covers a method of treating or reducing pruritis in a mammal using an Nppb blocking agent, and several dependent claims specifying conditions and characteristics related to the method.
Method of treating or reducing pruritis using an antibody or antibody fragment
A method for treating or reducing pruritis in a mammal by administering at least one Nppb blocking agent in an amount effective to treat or reduce pruritis, wherein the Nppb blocking agent is an antibody or antibody fragment that specifically binds to Nppb or natriuretic polypeptide receptor A (Npra).
Specific pruritis associations and inducers
The method applies to pruritis associated with fungal or Trichomonas skin infections, eczema, psoriasis, renal failure, liver damage or disease, AIDS, polycythemia vera, diabetes, hyperthyroidism, cancer, chemotherapy, and pruritis induced by pruritogens such as histamine, chloroquine, endothelin (ET-1), 2-methyl serotonin (5HT), SLIGRL-NH2 (PAR2), compound 48/80, or mediated by interleukin (IL)-31.
Preferred mammal subject
The mammal treated by the method is preferably a human.
The claims cover the inventive feature of using an antibody or antibody fragment that specifically binds to Nppb or Npra as an Nppb blocking agent to treat or reduce pruritis in mammals, particularly humans, under various causes and associated conditions.
Stated Advantages
Administration of Nppb blocking agents effectively treats, reduces, or prevents pruritis in mammals.
The Nppb blocking agents can target a broad range of pruritogens and pruritis-associated conditions, including chronic itch.
The Nppb blocking agents can be non-neurotoxic, avoiding ablation of cells, providing safer therapeutic options.
The in vitro method facilitates identification of compounds inhibiting Nppb activity, enabling discovery of novel therapeutics.
Documented Applications
Treatment, reduction, or prevention of transient or chronic pruritis in mammals.
Treatment of pruritis associated with skin infections (e.g., fungal infections, Trichomonas), psoriasis, atopic dermatitis, renal failure, liver damage or disease, AIDS, polycythemia vera, diabetes, hyperthyroidism, cancer, and chemotherapy.
Treatment of pruritis induced by pruritogens including histamine, chloroquine, endothelin (ET-1), 2-methyl serotonin (5HT), SLIGRL-NH2 (PAR2), and compound 48/80.
Treatment of pruritis mediated by cytokines such as interleukin (IL)-31.
Use of the in vitro screening method to identify compounds that inhibit Nppb activity as candidate therapeutics for pruritis.
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