Nitroxide Radical as a Treatment for Neurodegeneration

Background:
The Human Iron Metabolism Section of the National Institute of Child Health and Human Development (NICHD) is seeking statements of capability or interest from parties interested in collaborative research to obtain pre-clinical data to be used to further develop, evaluate, or commercialize nitroxide radicals as a treatment for neurodegeneration and other neurological disorders related to iron-deficiencies.

Technology:
Over 22 million people suffer from neurodegenerative diseases worldwide, and in 2050, this number could triple due to increased life expectancy and an increased aging population.

This invention describes the use of a nitroxide radical to treat or prevent the progression of neurodegeneration characterized by a deficiency in iron regulatory protein 2 (IRP 2) function. The inventors discovered that mice with adult-onset neurodegeneration and microcytic anemia caused by deletion of IRP 2 regain activity of iron regulatory protein 1 (IRP 1), a second iron regulatory protein, after eating food formulations containing specific nitroxide radicals. This discovery lends credibility to the idea that human patients who have neurodegeneration from a similar cause could be treated with the same dietary supplement and/or an oral formulation to restore proper iron balance to the brain. The inventors discovered that the nitroxide agent prevents the progression of neurodegeneration by attacking inhibitory iron-sulfur clusters found on IRP 1 thereby allowing IRP 1 to bind to iron responsive elements found on transcripts that encode iron metabolism proteins that regulate cellular iron homeostasis in the brain.

In addition to adult-onset neurodegeneration, nitroxide radicals have the potential to be used in the treatment of other neurological disorders caused by abnormal brain iron metabolism, including Alzheimer's and Parkinson's disease, erythropoietic protoporphyria, neuronal brain iron accumulation (formerly known as Hallevorden Spatz disease)and Friedreich ataxia. Additionally, nitroxide radicals could be used to treat refractory anemias caused by abnormal iron metabolism.

Further R&D Needed:
The inventors plan to search for humans with IRP2 mutations by sequencing genetic samples from patients with anemia, neurodegeneration and erythropoietic protoporphyria. When such patients are identified, they will be treated early in the course of disease to prevent neurodegeneration and disability.

R&D Status:
Pre-clinical discovery

IP Status:
U.S. Provisional Application No. 60/894,134 filed 09 Mar 2007

Value Proposition--Solution:

• Versatile method of treating adult-onset neurodegeneration that can be administered as a dietary supplement or as an oral formulation.
• Ability to treat numerous, debilitating neurological disorders.

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #612 JC

Updated 02/01/2008