# US 2008/0187939 A1 · Protein kinase c gamma as a biomarker for neuropsychological and cognitive functions in the central nervous system

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- Number: US 2008/0187939 A1
- Document ID: US20080187939A1
- Status: Published application
- Kind: A1
- Application number: 12/020,348
- Filed: 2008-01-25
- Published: 2008-08-07
- Earliest claimed: 2007-01-25
- Inventors: Kathleen S. Madden
- Web page: https://patentgrep.com/patent/US20080187939A1

## CPC

- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2333/9121: with an alcohol group as acceptor (2.7.1), e.g. general tyrosine, serine or threonine kinases
- G01N 2800/28: Neurological disorders
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Embodiments of the present invention are directed to a biological marker, the gamma isoform of protein kinase C (PKCg), which surprisingly allows rapid identification of compromised cognitive, behavioral, and neuropsychological functions under conditions associated with acute, transient hypoxia in humans. It was surprisingly discovered that PKCg is released from neural cells and can be detected in peripheral blood after hypoxic events unrelated to the reduction or elimination of blood flow through affected tissues. Embodiments of this invention are also directed to a broad range of clinical applications, particularly in emergency medicine. Other embodiments are related to compositions and methods for distinguishing between hypoxic encephalopathies and conditions arising from neuroanatomical/structural anomalies and/or incidental pathologies, for example, alcohol intoxication.

## Claims

### Claim 1

A method for assessing an abnormality of a neurological or cognitive function of the central nervous system of a patient comprising:
contacting a sample obtained from said patient with a binding partner capable of forming a complex with protein kinase C gamma (PKCg) to form a PKCg/binding partner complex; and
detecting PKCg/binding partner complex formed and determining the presence of the abnormality in the neurological or cognitive function assessed.

### Claim 2 (depends on 1)

The method of claim 1, wherein the abnormality is selected from the group consisting of an abnormal behavioral, neuropsychological, or neuropsychiatric function, a movement disorder, a drug-induced or toxin-induced disorder, short-term memory loss, an encephalopathy, and combinations thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the abnormal neurological or cognitive function is associated with chronic hypoxia.

### Claim 4 (depends on 3)

The method of claim 3, wherein the chronic hypoxia is associated with a breathing disorder, apnea, a pulmonary disorder, a surgical procedure, administration of a medication, a change in altitude or barometric pressure or a combination thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein the abnormality is not connected with an ischemic event or the restriction of blood flow to the central nervous system.

### Claim 6 (depends on 1)

The method of claim 1, wherein the patient is a mammal.

### Claim 7 (depends on 6)

The method of claim 6, wherein the mammal is a human.

### Claim 8 (depends on 1)

The method of claim 1, wherein the sample is a sample of peripheral blood.

### Claim 9 (depends on 1)

The method of claim 1, wherein the sample is a sample of retinal fluid.

### Claim 10 (depends on 1)

The method of claim 1, wherein the binding partner is an anti-PKCg antibody or antibody fragment.

### Claim 11 (depends on 1)

The method of claim 1, wherein said anti-PKCg antibody is detectably labeled.

### Claim 12 (depends on 1)

The method of claim 1, further comprising quantitatively determining the amount of PKCg/binding partner complex formed.

### Claim 13 (depends on 1)

The method of claim 1, further comprising determining the relative amount of PKCg/binding partner complex formed as compared with the amount of PKCg/binding partner complex of a control sample indicative of a normal neurological or cognitive function.

### Claim 14

A method for assessing the potential for impairment of a neurological or cognitive function of the central nervous system of a patient comprising:
contacting a sample obtained from the patient with a binding partner capable of forming a binding complex with protein kinase C gamma (PKCg) to form a PKCg/binding partner complex;
determining the quantity of PKCg/binding partner complex formed; and
assessing the potential for impairment of the neurological or cognitive function from the quantity of PKCg/binding partner complex formed.

### Claim 15 (depends on 14)

The method of claim 14, further comprising comparing the amount of PKCg/binding partner complex formed with an amount of PKCg/binding partner complex formed with a control sample, wherein said control sample is indicative of a known impairment of a neurological or cognitive function of the central nervous system.

### Claim 16 (depends on 14)

The method of claim 14, further comprising monitoring the amount of PKCg/binding partner complex formed over a period of time.

### Claim 17

A method for diagnosing a disorder of a neurological or cognitive function of the central nervous system of a patient comprising:
contacting a sample obtained from said patient with a binding partner capable of forming a binding complex with PKCg to form a PKCg/PKCg binding partner complex, wherein detection of a PKCg/PKCg binding partner complex is diagnostic of said disorder.

### Claim 18

A kit for diagnosis of a disorder of the neurological or cognitive function of the central nervous system of a patient comprising:
a first substrate having immobilized thereon an anti-PKCg antibody or antibody fragment for contact with a sample obtained from the patient;
a detectable label that is capable of binding to a PKCg/PKCg antibody complex;
a second substrate which has bound thereto a PKCg/binding partner complex which is detectably labeled at a detection level that is representative of a disorder of a neurological or cognitive function of the central nervous system of a similar patient.

### Claim 19 (depends on 18)

The kit of claim 18, further comprising a second anti-PKCg antibody reactive with another epitope of PKCg.

### Claim 20 (depends on 18)

The kit of claim 18, wherein said first antibody is immobilized on a solid support.

### Claim 21 (depends on 20)

The kit of claim 20, wherein the solid support is selected from the group consisting of a plastic multiwall plate, plastic or glass beads or rods, and a plastic or glass film.

### Claim 22 (depends on 18)

The kit of claim 18, wherein the antibody or antibody fragment is labeled

### Claim 23 (depends on 18)

The kit of claim 18, further comprising one or more additional substrates each of which has bound thereto a PKCg/binding partner complex which is detectably labeled at a detection level that is representative of another disorder of a neurological or cognitive function of the central nervous system of a similar patient.
