System for seizure suppression

• US 7,892,764 B2
• Filed: 11/21/2007
• Issued: 02/22/2011
• Est. Priority Date: 11/21/2006
• Status: Active Grant

• Current Assignee: Legacy Emanuel Hospital and Health Center
• Original Assignee: Legacy Emanuel Hospital and Health Center
• Inventors: Xiong, Zhigang, Simon, Roger P.
• Primary Examiner(s): Ulm; John D
• Application Number:
  US11/944,332
• Publication Number:
  US 20080242588A1
• Time in Patent Office: 1,189 Days
• Field of Search: None
• US Class Current: 435/7.2
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: C40B 30/06 by measuring effects on living organisms, tissues or cells
• CPC Class Codes: G01N 2800/2857 Seizure disorders; Epilepsy
• CPC Class Codes: G01N 33/5082 Supracellular entities, e.g. tissue, organisms
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

Systems, including methods and compositions, for seizure suppression, such as inhibition of epileptic seizures. In some embodiments, the methods may provide a screen for anti-seizure drugs. One or more compositions may be selected based on an ability to affect a response of biological cells to a change in extracellular pH and/or to affect an activity of at least one acid sensing ion channel (ASIC). Based on the one or more compositions selected, at least one drug candidate may be assayed for inhibition of seizure-like electrical activity and/or seizures. In some embodiments, the methods and compositions may, respectively, administer and provide an effective amount of PcTX1, a peptide derivative of PcTX1 amiloride, an amiloride derivative, or a combination thereof to a subject prone to seizures and/or having a seizure, in order to suppress seizure activity.

Claims

1. A method of screening for anti-seizure drugs, comprising:

testing a library of compounds for an ability to inhibit an ion channel activity of at least one acid sensing ion channel (ASIC) at a pH that activates the ASIC;

selecting one or more compounds from the library that have the ability to inhibit in a manner selective or specific for the ASIC relative to most or all ion channels that are not ASICs; and

assaying the one or more compounds for inhibition of seizure-like electrical activity and/or seizures.

2. The method of claim 1, wherein the step of selecting includes a step of selecting one or more compounds each capable of inhibiting acid sensing ion channel 1a (ASIC1a).

3. The method of claim 1, wherein the step of assaying includes a step of assaying at least one analog of at least one of the one or more compounds selected.

4. The method of claim 1, wherein the step of testing includes a step of performing optical assays, and wherein the step of selecting one or more compounds is based on results from the optical assays.

5. The method of claim 1, wherein the step of assaying includes a step of assaying the one or more compounds in a clinical trial.

6. The method of claim 1, wherein the step of assaying includes a step of assaying the one or more compounds on a tissue explant from brain.

7. The method of claim 1, wherein the step of assaying includes a step of using a patch-clamp technique.

8. The method of claim 1, wherein the step of assaying includes a step of administering a peptide analog of PcTX1 or an amiloride analog to a subject.

9. The method of claim 8, wherein the step of administering includes a step of administering an amiloride analog to the subject.

10. The method of claim 8, wherein the step of administering includes a step of administering an amiloride derivative with the structural formula

11. The method of claim 8, wherein the step of administering includes a step of administering parenterally.

12. The method of claim 8, wherein the step of administering includes a step of administering a peptide analog of PcTX1 to the subject.

13. The method of claim 8, further comprising a step of selecting a person with epilepsy, wherein the step of administering is performed on the person with epilepsy.

14. The method of claim 8, wherein the step of administering includes a step of administering while the subject is not having a seizure.

15. The method of claim 1 , wherein the step of testing includes a step of testing the library of compounds using biological cells modified to express the at least one acid sensing ion channel (ASIC).

16. The method of claim 15, wherein the step of testing uses biological cells that have been modified by introduction of a nucleic acid encoding acid sensing ion channel 1a (ASIC1a).

17. The method of claim 1, wherein the step of assaying includes a step of assaying the one or more compounds for an ability to inhibit an onset of seizure-like electrical activity and/or seizures.