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Title: US5834457: Method of modulating radical formation by mutant cuznsod enzymes
[ Derwent Title ]

Country: US United States of America

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14 pages

 
Inventor: Bredesen, Dale E.; Rancho Santa Fe, CA
Valentine, Joan S.; Los Angeles, CA
Wiedau-Pazos, Martina; Los Angeles, CA
Goto, Joy J.; Los Angeles, CA
Gralla, Edith B.; Los Angeles, CA

Assignee: The Regents of the University of California, Oakland, CA
The Burnham Institute, La Jolla, CA
other patents from UNIVERSITY OF CALIFORNIA, THE REGENTS OF (599425) (approx. 4,840)
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Published / Filed: 1998-11-10 / 1996-01-26

Application Number: US1996000592704
IPC Code: Advanced: A61K 31/05; A61K 31/13; A61K 31/145; A61K 31/175; A61K 31/198; A61K 31/325; A61K 31/355; A61K 31/375; A61K 31/40; A61K 31/4015; A61K 31/444; A61P 21/04; C12N 9/99;
Core: A61K 31/045; A61K 31/185; A61K 31/352; A61K 31/4427; A61P 21/00; more...
IPC-7: A01N 43/04;

ECLA Code: A61K31/13; A61K31/05; A61K31/175; A61K31/198; A61K31/325; A61K31/355; A61K31/375; A61K31/40+A; A61K31/4015; A61K31/444;

U.S. Class: Current: 514/188; 514/184; 514/499;
Original: 514/188; 514/184; 514/499;

Field of Search: 514/044,365,562,227.2,188,184,499

Priority Number:
1996-01-26  US1996000592704

Abstract:     Familial amyotrophic lateral sclerosis (FALS)-associated mutant CuZnSODs, A4V and G93A, have been discovered to catalyze the generation of hydroxyl radical from hydrogen peroxide at higher rates than that of wild type CuZnSOD. The copper chelator diethyldithiocarbamate (DDC) has been found to inhibit both radical generation and SOD activity of mutant CuZnSODs A4V and G93A at DDC concentrations significantly lower than those required to inhibit wild type CuZnSOD enzyme. In a neural cell culture model of FALS, DDC reverses the effect of four FALS-associated mutants, but does not alter the survival of cells expressing only wild type CuZnSOD. Thus, radical formation may be modulated and ALS treated in subjects with a mutant CuZnSOD enzyme by the administration of copper chelating agents. Treatment can also be affected by the administration of radical scavenging agents, or the administration of expression inhibitors specific for the mutant genes.

Attorney, Agent or Firm: Reiter, Stephen E.Gray Cary Ware & Freidenrich ; Raymer, Gregory P. ;

Primary / Asst. Examiners: Woodward, Michael P.; Brumback, Brenda G.
Maintenance Status: CC Certificate of Correction issued

INPADOC Legal Status: Show legal status actions          Buy Now: Family Legal Status Report

Designated Country: AL AM AP AT AZ BA BB BG BR BY CN CU CZ EE FI GE HU IL IS KE KG KP KR KZ LC LK  CH DE DK ES FR GB GR IE IT LI 

Family: Show 7 known family members
First Claim:
Show all 20 claims		 That which is claimed is:     1. A method of modulating radical formation in a subject previously determined to have a mutant CuZnSOD protein, said method comprising administering to said subject a copper chelating agent in an amount effective to modulate radical formation by said mutant CuZnSOD protein.

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Forward References: Show 2 U.S. patent(s) that reference this one

       
U.S. References: Go to Result Set: All U.S. references   |  Forward references (2)   |   Backward references (0)   |   Citation Link

       
Foreign References: None

Other Abstract Info: CHEMABS 127(12)156738Y

Other References:
  • Zhong et al., "bcl-2 inhibits death of central neural cells induced by multiple agents," Proc. Natl. Acad. Sci. USA, vol. 90, pp. 4533-4537, May 1993. (5 pages) Cited by 6 patents [ISI abstract]
  • Gurney et al., "Motor Neuron Degeneration in Mice That Express a Human Cu,Zn Superoxide Dismutase Mutation," Science, vol. 264, pp. 1772-1775, 17 Jun. 1994. (4 pages) Cited by 9 patents [ISI abstract]
  • Borchelt et al., "Superoxide dismutase 1 with mutations linked to familial amyotrohic lateral sclerosis possesses significant activity," Proc. Natl. Acad. Sci. USA, vol. 91, pp. 8292-8296, Aug. 1994. (5 pages) Cited by 8 patents [ISI abstract]
  • Rabizadeh, S., "Mutations associated with amyotrophic lateral sclerosis convert superoxide dismutase from an antiapoptotic gene to a proapoptoitic gene: Studies in yeast and neural cells," Proc. Natl. Acad. Sci. USA, vol. 92, pp. 3024-3028, Mar. 1995. (5 pages) [ISI abstract]
  • Nishida et al. "Characterization of three yeast copper-zinc superoxide dismutase mutatns analogous to those coded for in familial amyotrophic lateral sclerosis" Pro. Natl. Acad. Sci. USA. 91:9906-9910 (1994). (5 pages) [ISI abstract]
  • Pardo et al. "Superoxide dismutase is an abundant component in cell bodies, dendrites, and axons of motor neurons and in a subset of other neurons" Proc. Natl. Acad. Sci. USA 92: 954-958 (1995). (5 pages) [ISI abstract]
  • Misra. "Reaction of Copper-Zinc Superoxide Dismutase with Diethyldithiocarbamate" The Journal of Biological Chemistry 254 No. 22:11623-11628 (1979).
  • Collard et al. "Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis" Nature 375:61-64 (1995). (4 pages) Cited by 3 patents [ISI abstract]
  • Yim et al. "Enzyme Function of Copper, Zinc Superoxide Dismutase as a Free Radical Generator" The Journal of Biological Chemistry 268 No. 6:4099-4105 (1993). (7 pages) Cited by 2 patents [ISI abstract]
  • Conradi, et al., "Long-tme penicallamine-treatment in amyotrophic lateral sclerosis with parallel determination of lead in blood, plasma and urine", Acta Neurol. Scandinav., vol. 65, pp. 203-211, 1983.
  • Deng et al., "Two novel SOD1 mutations in patients with familial amyotrophic lateral sclerosis", Human Molecular Genetics, vol. 4, No. 6, pp. 1113-1116, 1995. (4 pages) [ISI abstract]


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