Treatment of Metal-Related Disorders and Amyloid- Aggregation

Case Number CH-049

Inventors: Hani Atamna, PhD

Patent No. Title Issue Date Country
Pending Polycarboxylated Porphyrins and Use Thereof in Treatment of Metal Toxicities   United States

Abstract
This invention provides a methods and compositions for preventing and treating Alzheimer's disease and other metal-related disorders.

All tissue types synthesize porphyrins and heme, although their capacities for regulation and biosynthesis vary. Heme and porphyrin metabolism are disturbed in Alzheimer's disease or after exposure to environmental toxins including metals. The mechanisms underlying these disturbances are not known, but porphyrin intermediates are excessively produced. No biological function has been ascribed for the porphyrins, other than as a precursor for heme, but the inventors found that endogenous porphyrins are excellent chelators for toxic (Al+++, Hg++ & Cd++) and physiological metals (Cu+, Mn+, Zn++), are capable of dismantling aggregated Amyloid- and are capable of preventing the aggregation of monomeric Amyloid-. The effect of porphyrins on Amyloid- is likely mediated by their ability to chelate metals.

In addition, it was found that heme itself will displace metals from the aggregated Amyloid- and disaggregate the complex. The inventors show that the changes in the biosynthesis of porphyrin and heme in Alzheimer's disease are a response to the pathological conditions of the brain and suggest that porphyrins can be used in prevention and treatment of Alzheimer's disease and other metal-related disorders.

Advantage
The invention provides a method for increasing an amount of metal-binding, polycarboxylated porphyrin in an individual comprising: (a) determining whether the individual is subject to or predisposed to such a metal-binding toxicity; (b) increasing the level of metal-binding polycarboxylated porphyrin in the individual; and (c) detecting a resultant increase in the amount of the metal-binding, polycarboxylated porphyrin in the individual.

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