Compounds, compositions and methods for treating oxidative DNA damage disorders

Abstract

Compounds, compositions, and formulations, and accompanying methods useful for treating disorders arising from oxidative DNA damage, including oxidative DNA damage resulting from ionizing radiation or other therapy are described herein.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 61 / 493,169 filed Jun. 3, 2011. The disclosure of which is incorporated herein by reference.TECHNICAL FIELD[0002]The present invention relates to compounds, compositions and formulations useful for treating disorders arising from oxidative DNA damage, including oxidative DNA damage resulting from ionizing radiation or other therapy.BACKGROUND AND SUMMARY OF THE INVENTION[0003]Evidence in patients and in animal models demonstrates that cancer therapies are often accompanied by neurological side effects. Two major neurological side effects are cognitive dysfunction, also referred to as “chemobrain,” and chemotherapy-induced peripheral neuropathy (CIPN). Two such therapies that cause neurological side effects include ionizing radiation and drugs that act through mechanisms causing DNA damage, such as platinum-containing drugs, taxanes, and the li...

AI Technical Summary

Benefits of technology

This patent text discusses the discovery of a protein called APE1 and its role in protecting sensory neurons from damage caused by chemotherapy and radiation. The text describes how modulating the expression of APE1 can reduce neurotoxicity and how inhibiting its redox function can enhance its neuroprotective activity. The technical effects of this patent include the development of compounds and methods to protect and treat neuronal damage, which can improve the quality of life for cancer survivors.

Problems solved by technology

Evidence in patients and in animal models demonstrates that cancer therapies are often accompanied by neurological side effects.

Furthermore, there are no standard and effective treatments available to prevent or reverse such therapy-induced neurotoxicity.

It has also been reported that IR can produce significant neurotoxicity, especially upon direct exposure to central nervous system tissues [6, 7].

Although many IR neurotoxicity studies focus on the CNS, such radiation therapy may also cause significant toxicity to peripheral neurons (autonomic, motor, or sensory neurons).

However, the mechanisms by which IR produces neurotoxicity remain undetermined.

Further, but without being bound by theory, it is believed herein that, in situ, radiation-induced oxidative damage to DNA may subsequently alter neuronal function and cause cell death.

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