Trpm4 channel inhibitors for stroke treatment

a stroke and channel inhibitor technology, applied in the field of stroke treatment, can solve the problems of increasing the risk of stroke, the inability of most people to be fully functional, and the need for significant rehabilitation, so as to prolong the therapeutic time window for reperfusion, reduce the volume of infarcts, and increase the angiogenesis of subjects

Inactive Publication Date: 2019-07-18
SINGAPORE HEALTH SERVICES PTE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0027]In another preferred embodiment of the method of the invention, the treatment reduces infarct volume in the subject.
[0028]In another preferred embodiment of the method of the invention, the treatment extends the therapeutic time window for reperfusion.

Problems solved by technology

Stroke is a major health problem worldwide.
For those stroke patients who survive, most are likely to be left disabled and in need of significant rehabilitation.
After that, reperfusion greatly increases cerebral edema and the risk of hemorrhagic transformation which are mainly caused by vascular damage.
However, numerous attempts from both pharmaceutical companies and stroke research community have failed to achieve this goal.
Activation of TRPM4 in SCI and EAE results in unchecked ion influx and subsequently leads to oncotic cell death.
Cerebral edema following brain injury is bound to cell death.
Edema resulting from ischemic stroke leads to tissue damage and worsens neurological functions.

Method used

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  • Trpm4 channel inhibitors for stroke treatment
  • Trpm4 channel inhibitors for stroke treatment
  • Trpm4 channel inhibitors for stroke treatment

Examples

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examples

[0120]Standard molecular biology techniques known in the art and not specifically described were generally followed as described in Sambrook and Russell, Molecular Cloning: A Laboratory Manual, Cold Springs Harbor Laboratory, New York (2001).

Materials and Methods

Animal Model

[0121]This study was approved and performed in accordance with the guidelines of the Institutional Animal Care and Use Committee of the National Neuroscience Institute, Singapore. As per the approved protocol, male Wistar rats weighing approximately 300 g were subjected to permanent or transient middle cerebral artery occlusion (MCAO). Prior to surgery, the animals were anesthetized with ketamine (75 mg / kg) and xylazine (10 mg / kg) intra-peritoneally. Under an operating microscope, the left common carotid artery was exposed and temporarily ligated using a vascular clip (Aesculap, B. Braun, Germany). Next, the left external carotid artery (ECA) and internal carotid artery (ICA) were dissected from the surrounding t...

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Abstract

The present invention relates to methods for treating ischemic stroke including extension of the therapeutic time window for reperfusion. More particularly, the invention relates to a method of treating stroke in a subject by inhibiting the transient receptor potential melastatin 4 (TRPM4) channel. The present invention also provides uses of TRPM4 inhibitors, TRPM4 antibodies and kits for use in the methods of the invention.

Description

RELATED APPLICATIONS[0001]This application is a divisional of U.S. patent application Ser. No. 14 / 392,213, filed Dec. 23, 2015, which is a national stage filing under 35 U.S.C. 371 of International Application No. PCT / SG2014 / 000314, filed Jun. 30, 2014, which claims priority to Singapore Application No. 201305129-7, filed Jun. 28, 2013. The entire teaching of the above applications are incorporated herein by reference. International Application PCT / SG2014 / 000314 was published under PCT Article 21(2) in English.FIELD OF THE INVENTION[0002]The present invention relates to methods for the treatment of ischemic stroke including extension of the therapeutic time window for reperfusion. More particularly, the present invention relates to blocking the function of the TRPM4 channel to improve capillary integrity during the acute and chronic phase of stroke.BACKGROUND OF THE INVENTION[0003]Stroke is a major health problem worldwide. It is the 4th leading cause of death in Singapore. For thos...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K16/28C12N15/113A61K45/06A61K39/395A61K31/713
CPCC07K16/28C12N15/1138A61K45/06A61K39/3955A61K31/713C12N2310/14C07K2317/24C07K2317/77C07K2317/34C07K2317/74C07K2317/76A61K2039/505A61P25/00
Inventor LIAO, PINGLOH, KOK POH
Owner SINGAPORE HEALTH SERVICES PTE
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