Methods of increasing endogenous erythropoietin (EPO)

Abstract

The present invention relates to methods for treating erythropoietin-associated conditions by increasing endogenous erythropoietin in vitro and in vivo. Methods for treating, pretreating or preconditioning, or preventing erythropoietin-associated conditions are also included. Compounds for use in these methods are provided, as are methods of identifying such compounds.

Description

[0001] This application claims the benefit of U.S. Provisional Application Serial No. 60 / 349,659, filed on 16 Jan. 2002; U.S. Provisional Application Serial No. 60 / 386,488, filed on 5 Jun. 2002; U.S. Provisional Application Serial No. 60 / 337,082, filed on 6 Dec. 2001; and U.S. Provisional Application Serial No. 60 / 359,683, filed on 25 Feb. 2002; each of which is incorporated by reference herein in its entirety.[0002] The present invention relates to methods for increasing endogenous erythropoietin, ex vivo and in vivo, and to compounds that can be used in the methods.[0003] Erythropoietin (EPO), a naturally occurring hormone, stimulates the production of red blood cells (erythrocytes), which carry oxygen throughout the body. EPO is normally secreted by the kidneys, and endogenous EPO is increased under conditions of reduced oxygen (hypoxia). All types of anemia are characterized by the blood's reduced capacity to carry oxygen, and thus are associated with similar signs and symptoms,...

AI Technical Summary

Benefits of technology

0099] The present methods can be used to increase endogenous EPO in a subject undergoing a specific treatment or procedure, prophylactically or concurrently, for example, an HIV-infected anemic patient being treated with azidothymidine (zidovudine) or other reverse transcriptase inhibitors, an anemic cancer patient receiving cyclic cisplatin- or non-cisplatin-containing chemotherapeutics, or an anemic or non-anemic patient scheduled to undergo surgery. Methods of increasing endogenous EPO can also be used to prevent, pretreat, or treat EPO-associated conditions associated with nerve damage or neural tissue degeneration including, but not limited to, stroke, trauma, epilepsy, spinal cord injury, and neurodegerative disorders.

0100] Additionally, the methods can be used to increase endogenous EPO levels in an anemic or non-anemic patient scheduled to undergo surgery to reduce the need for allogenic blood transfusions or to facilitate banking of blood prior to surgery. The small decreases in hematocrit that typically occur after presurgical autologous blood donation do not stimulate an increase in endogenous EPO or in compensatory erythropoiesis. However, preoperative stimulation of endogenous EPO would effectively increase erythrocyte mass and autologous donation volumes while

Problems solved by technology

All types of anemia are characterized by the blood's reduced capacity to carry oxygen, and thus are associated with similar signs and symptoms, including pallor of the skin and mucous membranes, weakness, dizziness, easy fatigability, and drowsiness, leading to a decrease in quality of life.

Subjects with severe cases of anemia show difficulty in breathing and heart abnormalities.

Various conditions can cause the destruction of erythrocytes (hemolysis), thus leading to anemia.

In addition, there are unusual situations in which the body produces antibodies against its own erythrocytes, resulting in hemolysis

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