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Stimulation for treating and diagnosing conditions

a technology for diagnosing conditions and stimuli, applied in the field of medical procedures and electronic devices, can solve the problems of affecting the treatment effect of cns metastases, the ineffective or less effective of certain non-surgical brain treatments based on systemic introduction of compounds through the bloodstream, and the bbb affecting the passage of many agents, so as to improve the oxygen supply to neurons and other tissues, improve the effect of cortical blood flow and reduce the effect of bbb

Inactive Publication Date: 2005-07-21
BRAINSGATE LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0121] The SPG is a neuronal center located in the brain behind the nose. It consists of parasympathetic neurons innervating the middle cerebral and anterior cerebral lumens, the facial skin blood vessels, and the lacrimal glands. Activation of this ganglion is believed to cause vasodilation of these vessels. A second effect of such stimulation is the opening of pores in the vessel walls, causing plasma protein extravasation (PPE). This effect allows better transport of molecules from within these blood vessels to surrounding tissue.
[0682] configure the signal so as to cause an increase in molecular passage between cerebrospinal fluid (CSF) of the subject and a tissue of the subject, so as to facilitate the diagnosis of the CNS condition.

Problems solved by technology

Because of the BBB, certain non-surgical treatments of the brain based upon systemic introduction of compounds through the bloodstream have been ineffective or less effective.
For example, chemotherapy has been relatively ineffective in the treatment of CNS metastases of systemic cancers (e.g., breast cancer, small cell lung cancer, lymphoma, and germ cell tumors), despite clinical regression and even complete remission of these tumors in non-CNS systemic locations.
Therefore, based both on their lipid solubilities and molecular masses, the passage of many agents is impeded by the BBB.
Non-surgical treatment of neurological disorders is generally limited to systemic introduction of compounds such as neuropharmaceuticals and other neurologically-active agents that might remedy or modify neurologically-related activities and disorders.
Such treatment is limited, however, by the relatively small number of known compounds that pass through the BBB.
Even those that do cross the BBB often produce adverse reactions in other parts of the body or in non-targeted regions of the brain.
However, due to the inherent limitations of each of the aforementioned procedures, there is still a need for more generic, effective, and predictable ways to cross the BBB.
Despite this emerging perspective, insufficient effort has been made in identifying factors responsible for Aβ accumulation in the brain.
Nevertheless, this evidence is far from definitive, and it is clear that other factors are involved.
Although the neuronal and synaptic loss is universally recognized as the primary cause of the decline of cognitive functions, the cellular, biochemical, and molecular events responsible for this neuronal and synaptic loss are subject to fierce controversy.
On the other hand, a number of studies showed that amyloid can be directly toxic to neurons, resulting in behavioral impairment (Ma et al., Neurobiol Aging 17: 773-780, 1996, which is incorporated herein by reference).
In spite of these compelling genetic data, it is still unclear whether Aβ generation and amyloid deposition are the primary cause of neuronal death and synaptic loss observed in AD.
Moreover, the biochemical events leading to Aβ production, the relationship between APP and the presenilins, and between amyloid and neurofibrillary tangles are poorly understood.
Thus, the picture of interactions between the major Alzheimer proteins is very incomplete, and it is clear that a large number of novel proteins are yet to be discovered.
The diagnosis of Alzheimer's disease during life is more difficult than at autopsy since the diagnosis depends upon inexact clinical observations.
The necessity for repeated evaluation is costly, generates anxiety, and can be frustrating to patients and their families.
Furthermore, the development of an appropriate therapeutic strategy is hampered by the difficulties of rapid diagnosis, particularly in the early stages where early intervention could leave the patient with significant intellectual capacity and a reasonable quality of life.
However, nerve growth factors are usually too large to cross the blood-brain barrier (BBB), a protective shield that restricts passage of molecules to the brain.
This relatively impermeable barrier has some drawbacks, however, when considering the therapeutic delivery of a molecule to the CNS.
The delivery of therapeutic molecules across the BBB has proven to be a major obstacle in treating various brain disorders.
Therefore, the BBB is a major impediment to the treatment of CNS diseases as many drugs are unable to reach this organ at therapeutic concentrations.
Many new neurotherapeutic agents are being discovered, but because of a lack of suitable strategies for drug delivery across the BBB, these agents are ineffective.
Such drugs will only become effective if strategies for brain delivery are developed in parallel.
These neurotoxic compounds are therefore not metabolized and removed from the body to the extent desired, and therefore continue to have undesired effects in the CNS.

Method used

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  • Stimulation for treating and diagnosing conditions
  • Stimulation for treating and diagnosing conditions
  • Stimulation for treating and diagnosing conditions

Examples

Experimental program
Comparison scheme
Effect test

example 1

Therapeutics (Glutamate Inhibitors)

[0810] Excitotoxicity is related to excessive activation of glutamate receptors which results in neuronal cell death. The physiological function of glutamate receptors is the mediation of ligand-gated cation channels with the concomitant influx of calcium, sodium and potassium through this receptor-gated channel. The influx of these cations is essential for maintaining membrane potentials and the plasticity of neurons which in itself plays a pivotal role in cognitive function of the central nervous system (Li, H. B. et al., Behav. Brain Res. 83: 225-228, 1997; Roesler, R. et al., Neurology 50: 1195, 1998; Wheal, H. V. et al., Prog. Neurobiol. 55: 611-640, 1998; Wangen, K et al., Brain Res. 99: 126-130, 1997). Excitotoxicity plays an important role in neuronal cell death following acute insults such as hypoxia, ischemia, stroke and trauma, and it also plays a significant role in neuronal loss in AIDS dementia, epilepsy, focal ischemia (Coyle, J. T....

example 2

Therapeutics β / γ Secretase Inhibitors

[0813] In a preferred embodiment of the present invention, methods for treatment of Alzheimer's disease target the formation of β-amyloid through the enzymes involved in the proteolytic processing of β-amyloid precursor protein. Compounds that inhibit β or γ secretase activity, either directly or indirectly, are used, in accordance with this embodiment, to control the production of β-amyloid. Advantageously, compounds that specifically target γ secretases, could control the production of β-amyloid. Typically, such inhibition of β or γ secretases reduces production of Aβ, which, in turn, reduces or prevents the neurological disorders associated with Aβ protein.

[0814] Compelling evidence accumulated during the last decade revealed that Aβ is an internal polypeptide derived from a type I integral membrane protein, termed b amyloid precursor protein (APP). P APP is normally produced by many cells both in vivo and in cultured cells, derived from var...

example 3

Therapeutics (NMDA-Receptor Blocker)

[0822] U.S. Patent Application Publication 2002 / 0035145 to Tsai et al., describes a method to treat various neuropsychiatric disorders, including Alzheimer's disease. Their description relates that neuropsychiatric disorders characterized by a deficit in neurotransmission via the NMDA receptor can be alleviated by a compound that acts as an agonist of the glycine site on the NMDA receptor or an inhibitor of glycine uptake. The compound is either a partial agonist such as D-cycloserine, which can be used at a dosage of 105-500 mg, or a full agonist (e.g., D-serine or D-alanine) that is selective for the NMDA receptor (compared to the inhibitory glycine receptor and other receptors), or a glycine uptake inhibitor (e.g., N-methylglycine). They describe methods for treating neuropsychiatric disorders in patients (i.e., humans). Examples of disorders that can be treated by the methods they describe include schizophrenia, Alzheimer's disease, autism, d...

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PUM

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Abstract

A method is provided for facilitating a diagnosis of a condition of a subject, including applying a current to a site of the subject selected from the list consisting of: a sphenopalatine ganglion (SPG) of the subject, and a neural tract originating in or leading to the SPG, and configuring the current to increase conductance of molecules from brain tissue of the subject through a blood brain barrier (BBB) of the subject into a systemic blood circulation of the subject. The method also includes sensing a quantity of the molecules from a site outside of the brain of the subject, following initiation of application of the current.

Description

CROSS-REFERENCES TO RELATED AND APPLICATIONS [0001] The present application: [0002] (a) is a continuation-in-part of (i) International Patent Application PCT / IL03 / 00338, filed Apr. 25, 2003, (ii) International Patent Application PCT / IL03 / 00508, filed Jun. 13, 2003, and (iii) U.S. patent application Ser. No. 10 / 783,113, filed Feb. 20, 2004, and [0003] (b) claims priority from U.S. Provisional Patent Application 60 / 506,165 to Shalev, filed Sep. 26, 2003. [0004] The '338 application claims priority from (a) U.S. Provisional Patent Application 60 / 376,048 to Shalev, filed Apr. 25, 2002, and (b) U.S. Provisional Patent Application 60 / 461,232 to Gross et al., filed Apr. 8, 2003. [0005] The '508 application claims priority from (a) U.S. Provisional Patent Application 60 / 388,931, filed Jun. 14, 2002, and (b) U.S. patent application Ser. No. 10 / 294,310 to Gross et al., filed Nov. 14, 2002, which claims priority from: (i) U.S. Provisional Patent Application 60 / 400,167, filed Jul. 31, 2002, and...

Claims

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Application Information

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IPC IPC(8): A61BA61N1/04A61N1/18
CPCA61M5/14276A61M5/1723A61M2205/3303A61M2210/0618A61N1/36046A61N1/0526A61N1/0546A61N1/0548A61M2210/0693
Inventor SHALEV, ALON
Owner BRAINSGATE LTD
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