US 8,026,217 B2 · Compositions and methods for treating neural anoxia and spreading depression

Abstract

Compositions and methods for protecting neural tissue (e.g., neurons) from anoxia and spreading depression (SD) involve inhibiting the cGMP-dependent protein kinase (PKG) pathway. It was discovered that the PKG pathway plays a crucial role in regulating SD and tolerance to anoxia in the central nervous system (CNS). Inhibition of the PKG pathway greatly reduces SD and increases tolerance to anoxia (i.e., hypoxia), while activation of the pathway exacerbates SD pathology. The compositions and methods can be used to treat any condition associated with SD or anoxia, including stroke, spinal cord injury, neurogenerative disease, dizziness, headaches, and migraines.

Claims6

Dependent claims

A method comprising administering a PKG pathway pharmacological inhibitor selected from the group consisting of:

KT5823;
(Rp)-8-bromo-PET-cyclic GMPS;
(Rp)-8-pCPT-cyclic GMPS, TEA;
Rp-8-Br-cGMPS, Na;
DT-3;
DT-2;
amino acid sequence RKRARKE (SEQ ID NO:
5);
Okadaic acid;
Microcystin;
Calyculin;
Cantharidin;
4H-8-Bromo-1,2,4-oxadiazolo(3,4-d)benz(b)(1,4)oxazin-1-one;
1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ);
and 6-Anilino-5,8-quinolinequinone to a patient having a medical condition selected from the group consisting of:
neuronal damage from spinal cord injury, neuronal damage from stroke, neural anoxia, spreading depression, and migraine, in an amount effective for preventing failure of neural function associated with one or both of neural anoxia and spreading depression in the patient.

13 more elements

Dependencies are inferred from the claim text.

Facts

Application

12/245,427Filed 3 Oct 2008 · us provisional application

Priority

3 Oct 2007

Published

US 2009/0124558 A114 May 2009

Granted

27 Sep 2011

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

A61K 31/351
Having six-membered rings with one oxygen as the only ring hetero atom: not condensed with another ring
A61K 31/4985
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrazines or piperazines…
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings
A61K 38/08
Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof: peptides having 5 to 11 amino acids

Compositions and methods for treating neural anoxia and spreading depression

Life of this patent

Compositions and methods for treating neural anoxia and spreading depression

Life of this patent

Abstract

Claims6