CA2273622A1 - Inhibition of nmda receptor signalling in reducing neuronal damage - Google Patents

Inhibition of nmda receptor signalling in reducing neuronal damage Download PDF

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Publication number
CA2273622A1
CA2273622A1 CA002273622A CA2273622A CA2273622A1 CA 2273622 A1 CA2273622 A1 CA 2273622A1 CA 002273622 A CA002273622 A CA 002273622A CA 2273622 A CA2273622 A CA 2273622A CA 2273622 A1 CA2273622 A1 CA 2273622A1
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CA
Canada
Prior art keywords
nmda receptor
precursor therefor
agent
neuron
neuronal
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002273622A
Other languages
French (fr)
Other versions
CA2273622C (en
Inventor
Michael Tymianski
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NoNO Inc
Original Assignee
Michael Tymianski
2056954 Ontario Ltd.
Nono, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Michael Tymianski, 2056954 Ontario Ltd., Nono, Inc. filed Critical Michael Tymianski
Priority to CA2273622A priority Critical patent/CA2273622C/en
Publication of CA2273622A1 publication Critical patent/CA2273622A1/en
Priority to US10/208,374 priority patent/US7595297B2/en
Priority to US10/930,192 priority patent/US7510824B2/en
Priority to US11/894,818 priority patent/US7846897B2/en
Priority to US12/392,988 priority patent/US8071548B2/en
Priority to US12/557,884 priority patent/US8648043B2/en
Priority to US13/286,071 priority patent/US20120302504A1/en
Application granted granted Critical
Publication of CA2273622C publication Critical patent/CA2273622C/en
Priority to US14/279,243 priority patent/US20150190459A1/en
Priority to US15/292,062 priority patent/US20170239316A1/en
Priority to US15/956,563 priority patent/US20180369319A1/en
Anticipated expiration legal-status Critical
Priority to US16/578,318 priority patent/US20200222492A1/en
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals

Abstract

A method of inhibiting the binding between N-methyl-D-aspartate receptors and neuronal proteins in a neuron the method comprising administering to the neuron an effective inhibiting amount of a peptide replacement agent for the NMDA receptor neuronal protein interaction domain or precursor therefor to effect the inhibition. The method is of value in reducing the damaging effect of injury to mammalian cells.

Claims (24)

1. A method of inhibiting the binding between N-methyl-D-aspartate receptors and neuronal proteins in a neuron said method comprising administering to said neuron an effective inhibiting amount of a peptide replacement agent for the NMDA receptor neuronal protein interaction domain or precursor therefor to effect said inhibition.
2. A method as defined in claim 1 wherein said neuron is damaged.
3. A method of reducing the damaging effect of ischemia or traumatic injury to the brain or spinal chord in a mammal, said method comprising treating said mammal with a non-toxic, damage-reducing, effective amount of a peptide replacement agent for the NMDA receptor neuronal protein interaction domain or precursor therefor.
4. A method as defined in claim 3 wherein said mammal is under the influence of neuronal cell damage.
5. A method as defined in any one of claims 1 to 4 wherein said NMDA receptor is bindable with membrane associated guanylate kinases.
6. A method as defined in claim 5 wherein said guanylate kinase is PSD-95.
7. A method as defined in claim 5 wherein said guanylate kinase is PSD-93.
8. A method as defined in claim 5 wherein said guanylate kinase is SAP102.
9. A method as defined in claim 5 wherein said guanylate kinase is SAP97.
10. A method as defined in any one of claims 1 - 9 wherein said replacement agent is a tSXV-containing peptide or precursor therefor.
11. A method as defined in claim 10 wherein said agent is KLSSLESDV or a precursor therefor.
12. A pharmaceutical composition comprising a peptide replacement agent for the NMDA receptor neuronal protein interaction domain in a mixture with a pharmaceutically acceptable carrier or a precursor therefor when used for reducing the damaging effect of an ischemic or traumatic injury to the brain or spinal chord of a mammal.
13. A composition as defined in claim 12 wherein said replacement agent is a tSXV-containing peptide or a precursor therefor.
14. A composition as defined in claim 13 wherein said agent is KLSSLESDV or a precursor therefor.
15. A composition as defined in any one of claims 12 - 14 further comprising antessapedia internalisation peptide.
16. A method of controlling the concentration of Ca2+ ions in the vicinity of ion channel pores of cells in vivo to prevent the diffusion of toxic amounts of said Ca2+ influx to prevent the triggering of neurotoxic phenomena, said method comprising administering an effective, non-toxic amount of a peptide replacement agent for the NMDA receptor neuronal protein interaction domain or precursor therefor.
17. A method as defined in claim 16 wherein said agent is a tSXV-containing peptide or precursor therefor.
18. A method as defined in claim 17 wherein said agent is KLSSLESDV or a precursor therefor.
19. A process for the manufacture of a pharmaceutical composition as defined in any one of the claims 12 - 15, said process comprising admitting said replacement agent with a pharmaceutically acceptable carrier therefor.
20. A method of inhibiting the binding between NMDA receptors and neuronal proteins in a neuron, said method comprising administering to said neuron an effective inhibiting amount of an antisense DNA to prevent expression of said neuronal proteins to effect inhibition of said binding.
21. A method of reducing the damaging effect of ischemia or traumatic injury to the brain or spinal chord in a mammal, said method comprising treating said mammal with a non-toxic, damage-reducing, effective amount of an antisense DNA to reduce the expression of NMDA receptor binding neuronal proteins and inhibition of binding between NMDA receptors and said neuronal proteins.
22. A method as defined in claim 21 wherein said neuron is damaged.
23. A method as defined in claim 21 and 22 wherein said antisense DNA reduces the expression of a membrane associated guanylate kinases bindable to said NMDA receptor.
24. A method as defined in claim 23 wherein said guanylate kinase is selected from PSD-95 and PSD-93.
CA2273622A 1999-06-02 1999-06-02 Inhibition of nmda receptor signalling in reducing neuronal damage Expired - Lifetime CA2273622C (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
CA2273622A CA2273622C (en) 1999-06-02 1999-06-02 Inhibition of nmda receptor signalling in reducing neuronal damage
US10/208,374 US7595297B2 (en) 1999-06-02 2002-07-30 Method of reducing injury to mammalian cells
US10/930,192 US7510824B2 (en) 1999-06-02 2004-08-31 Method of screening peptides useful in treating traumatic injury to the brain or spinal cord
US11/894,818 US7846897B2 (en) 1999-06-02 2007-08-20 Agents for reducing injury to mammalian cells
US12/392,988 US8071548B2 (en) 1999-06-02 2009-02-25 Method of reducing injury to mammalian cells
US12/557,884 US8648043B2 (en) 1999-06-02 2009-09-11 Method of reducing injury to mammalian cells
US13/286,071 US20120302504A1 (en) 1999-06-02 2011-10-31 Method Of Reducing Injury To Mammalian Cells
US14/279,243 US20150190459A1 (en) 1999-06-02 2014-05-15 Method Of Reducing Injury To Mammalian Cells
US15/292,062 US20170239316A1 (en) 1999-06-02 2016-10-12 Method Of Reducing Injury To Mammalian Cells
US15/956,563 US20180369319A1 (en) 1999-06-02 2018-04-18 Method of Reducing Injury to Mammalian Cells
US16/578,318 US20200222492A1 (en) 1999-06-02 2019-09-21 Method of Reducing Injury to Mammalian Cells

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CA2273622A CA2273622C (en) 1999-06-02 1999-06-02 Inhibition of nmda receptor signalling in reducing neuronal damage

Publications (2)

Publication Number Publication Date
CA2273622A1 true CA2273622A1 (en) 2000-12-02
CA2273622C CA2273622C (en) 2012-03-20

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
CA2273622A Expired - Lifetime CA2273622C (en) 1999-06-02 1999-06-02 Inhibition of nmda receptor signalling in reducing neuronal damage

Country Status (1)

Country Link
CA (1) CA2273622C (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001087285A2 (en) * 2000-05-12 2001-11-22 The Johns Hopkins University Inhibition of the interaction of psd93 and psd95 with the nnos and nmda receptors
US6942981B1 (en) 1999-05-14 2005-09-13 Arbor Vita Corporation Method of determining interactions with PDZ-domain polypeptides
EP1578365A2 (en) * 2002-11-14 2005-09-28 Arbor Vita Corporation Molecular interactions in neurons
US7494981B2 (en) 2000-05-12 2009-02-24 The Johns Hopkins University Inhibition of interaction of PSD93 and PSD95 with nNOS and NMDA receptors
US7510824B2 (en) 1999-06-02 2009-03-31 Nono Inc. Method of screening peptides useful in treating traumatic injury to the brain or spinal cord
US7595297B2 (en) 1999-06-02 2009-09-29 Michael Tymianski Method of reducing injury to mammalian cells
EP2385124A3 (en) * 1999-05-14 2012-06-27 Arbor Vita Corporation Peptides or peptide analogues for modulating the binding of a PDZ protein and a PL protein

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6942981B1 (en) 1999-05-14 2005-09-13 Arbor Vita Corporation Method of determining interactions with PDZ-domain polypeptides
US7432065B2 (en) 1999-05-14 2008-10-07 Arbor Vita Corporation Methods of identifying modulators of interaction between PDZ domain proteins and PL proteins
EP2385124A3 (en) * 1999-05-14 2012-06-27 Arbor Vita Corporation Peptides or peptide analogues for modulating the binding of a PDZ protein and a PL protein
US7514224B2 (en) 1999-05-14 2009-04-07 Arbor Vita Corporation Arrays of PDZ domain polypeptides
US7846897B2 (en) 1999-06-02 2010-12-07 Michael Tymianski Agents for reducing injury to mammalian cells
US20150190459A1 (en) * 1999-06-02 2015-07-09 Nono Inc. Method Of Reducing Injury To Mammalian Cells
US8648043B2 (en) 1999-06-02 2014-02-11 Nono Inc. Method of reducing injury to mammalian cells
US7510824B2 (en) 1999-06-02 2009-03-31 Nono Inc. Method of screening peptides useful in treating traumatic injury to the brain or spinal cord
US8071548B2 (en) 1999-06-02 2011-12-06 Nono, Inc. Method of reducing injury to mammalian cells
US7595297B2 (en) 1999-06-02 2009-09-29 Michael Tymianski Method of reducing injury to mammalian cells
US8148347B2 (en) 2000-05-12 2012-04-03 The Johns Hopkins University Inhibition of interaction of PSD93 and PSDS95 with nNOS and NMDA receptors
WO2001087285A2 (en) * 2000-05-12 2001-11-22 The Johns Hopkins University Inhibition of the interaction of psd93 and psd95 with the nnos and nmda receptors
US7494981B2 (en) 2000-05-12 2009-02-24 The Johns Hopkins University Inhibition of interaction of PSD93 and PSD95 with nNOS and NMDA receptors
WO2001087285A3 (en) * 2000-05-12 2002-08-15 Univ Johns Hopkins Inhibition of the interaction of psd93 and psd95 with the nnos and nmda receptors
EP1578365A4 (en) * 2002-11-14 2009-09-23 Arbor Vita Corp Molecular interactions in neurons
EP1578365A2 (en) * 2002-11-14 2005-09-28 Arbor Vita Corporation Molecular interactions in neurons

Also Published As

Publication number Publication date
CA2273622C (en) 2012-03-20

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