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