Nucleic acid constructs and cells, and methods utilizing same for modifying the electrophysiological function of excitable tissues

a technology of nucleic acid and constructs, which is applied in the field of nucleic acid constructs and cells, can solve the problems of damage to cells and/or channels of excitable tissues, no longer supporting normal electrophysiological functions, and severe effects on nerve signal function

Inactive Publication Date: 2004-02-12
GENEGRAFTS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since ion channels participate in numerous physiological processes, damage to cells and/or channels of excitable tissues can be a cause for numerous disorders.
For example, heart conditions, such as reentrant arrhythmia, are brought about by the damage or death of myocardial cells, which can no longer support normal electrophysiological function.
Secretion of factors from glandular ...

Method used

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  • Nucleic acid constructs and cells, and methods utilizing same for modifying the electrophysiological function of excitable tissues
  • Nucleic acid constructs and cells, and methods utilizing same for modifying the electrophysiological function of excitable tissues
  • Nucleic acid constructs and cells, and methods utilizing same for modifying the electrophysiological function of excitable tissues

Examples

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example 1

Cardiac Applications

[0133] Cardiac arrhythmias are rhythm disturbances that result from alteration of the electrophysiological substrate of the heart. These arrhythmias include bradyarrhythmias (slow heart rate) which result from abnormalities in impulse formation or conduction and tachyarrhythmias (high heart rate) which result from abnormalities in the electrophysiological substrate and which lead to the formation of tachyeardia via abnormal foci firing at high rate or via formation of reentry circuits.

[0134] Cardiac arrhythmia often results from damage to the electrophysiological tissue substrate of the heart. By transplanting cells transfected with various ionic channels of specific and predetermined properties, the methods of the present invention enable one to modify the electrophysiological properties of heart tissue and thus repair such arrhythmias. Thus, the present invention can be used to either increase excitability to treat bradyarrhythmias or modify the electrophysiolo...

example 2

Pancreas

[0166] Diabetes Mellitus is a metabolic disease in which carbohydrate utilization is reduced while utilization of lipid and protein enhanced. Diabetes Mellitus is caused by relative deficiency of insulin, and is characterized, in more severe cases, by chronic hyperglycemia, glycosuria, water and electrolyte loss, and various organ damage causing significant morbidity and mortality.

[0167] Gap junctions and junction-mediated cell-to-cell communications are obligatory features of gland cells, regardless of their secretory products. Studies on pancreatic islets and acinar cells indicate that cell-to-cell communication via gap junction channels is required for proper biosynthesis, storage and release of both insulin and amylase. However, the endocrine and exocrine portions of the pancreas show opposite connexin (Cx) and coupling changes in relation to the activation and inhibition of their secretory functions. These differences may be accounted for by the expression of connexin43...

example 3

CNS

[0174] Epilepsy

[0175] Epilepsy is a chronic disorder usually associated with some alteration of consciousness and characterized by paroxysmal brain dysfunction due to excessive neuronal discharge.

[0176] Astroglial cells contribute to neuronal maintenance and function in the normal and diseased brain. Gap junctions, formed predominantly by connexin43 between astroglias, provide important pathways which coordinate astroglial responses (Reuss et al, 2000, Glia May; 30(3):231-41). Neuronal-glial interactions play an important role in information processing in the CNS. Previous studies have indicated that electro-tonic coupling between locus ceruleus (LC) neurons is involved in synchronizing the spontaneous activity. Moreover, Spontaneous oscillations in the membrane potential were observed in a subset of glial cells. These oscillations were synchronous with the firing of neurons, insensitive to transmitter receptor antagonists and disrupted by carbenoxolone, a gap junction blocker. F...

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Abstract

A method of modifying the electrophysiological function of an excitable tissue region of an individual is provided. The method includes the step of implanting cells into the excitable tissue region. Each implanted cell is (a) capable of forming gap junctions with at least one cell of the excitable tissue region; and (b) capable of forming a functional ion channel or transporter, wherein the functional ion channel or transporter is capable of modifying the electrophysiological function of the excitable tissue region.

Description

FIELD AND BACKGROUND OF THE INVENTION[0001] The present invention relates to nucleic acid constructs and cells, and further to methods utilizing same for modifying the electrophysiological function of excitable tissues. More particularly, embodiments of the present invention relate to the use of cells having gap junctions and ion channels or transporters for modifying the electrophysiological function of excitable tissues.[0002] The biological cell membrane, the interface between the cell and its environment, is a complex biochemical entity one of whose major involvement is the directed transport of specific substances. A related major involvement of the cell membrane is the maintenance of chemical gradients, particularly electrochemical gradients, across this interface. These gradients are of great functional significance (e.g., in the production of action potentials in nerve and muscle cells).[0003] Ion channels are macromolecular protein pores, which span the cell membrane lipid ...

Claims

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Application Information

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IPC IPC(8): A61K38/00A61K48/00C07K14/705C12N5/02
CPCA61K38/00A61K48/00C07K14/705C12N5/0657C12N5/0697C12N2500/12C12Q1/6897C12N2502/1323C12N2502/1329C12N2502/99C12Q2565/631
Inventor FELD, YAIRGEPSTEIN, LIORMAROM, SHIMONFRANK, MEIRA
Owner GENEGRAFTS LTD
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