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Neuroprotective composition and method of use

a composition and neuroprotective technology, applied in the field of polyarginine and polyarginine/cysteine compositions, can solve the problems of inability to move one or more limbs on one side of the body, permanent dysfunction/damage of the brain, difficulty in understanding or formulating speech,

Inactive Publication Date: 2015-05-07
BROWN UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes a composition of a polyarginine peptide that can be used to treat neuronal injury and protect against glaucoma-related vision damage. The peptide contains between 5 and 9 arginine residues and may also have terminal cysteine residues linked by a disulfide bond. The peptide can be administered through various routes such as i.v. or eye drops. The technical effect of this invention is to provide a novel therapeutic agent that can protect against damage to the optic nerve and retina, which may lead to vision loss.

Problems solved by technology

As a result, and often worsening over time, brain injury becomes permanent dysfunction / damage.
In particular instances this is exhibited as an inability or reduced ability to move one or more limbs on one side of the body, inability to or difficulty in understanding or formulating speech, or an inability to see one side of the visual field.
In the case of stroke, secondary neuronal damage following the initial insult is a significant factor in patient decline and eventual death.
This decline manifests itself weeks to months following the initial stoke and, without effective therapeutic intervention, leads to a slow but continuous decline in the patients physical and mental health.
Recent reports, however, establish TBI as equally destructive in outcome in the more severe cases Current reports find that about 40% of people with TBI exhibit a continuing decline in both physical and mental capacity.
This represents a significantly higher incidence of dementia, in some instances is an aggravating factor in death.
In addition, alterations in the release of neurotransmitters particularly glutamate can cause excitotoxic neuronal cell death by causing free radicals generation and oxidative stress within these neurons that leads to neurodegeneration.

Method used

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  • Neuroprotective composition and method of use
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Examples

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Effect test

example 1

Stroke Patient

[0068]A 57 year old male enters the emergency room and is diagnosed with an ischemic event involving the middle cerebral artery, with symptomatology onset being under 1 hr. Immediately, the patient was administered an i.v. supplemented with poly-arginine (R(7)C-s-s-C, 5 mg / kg) while blood supply to the restricted area is restored.

[0069]Daily testing of cognitive and motor systems show no deficits in physical or mental capacities. In addition, CT / MRI imaging show no signs of lesioning in the affected region, immediately following recovery and that this was maintained and confirmed by follow-up imaging and behavior testing.

example 2

Post-Stroke Patient

[0070]A 64 year old woman is revived following stoke in her home by EMS and is rushed to the nearest hospital 80 miles away. Upon arriving at the hospital it is determined that the patient is showing signs of weakness on her left side. In addition she complains of having blurred vision and exhibits difficulty in speaking clearly. She is immediately started an i.v. and administered poly arginine (R(7))@ 4 mg / kg / hr over a period of 5 days to arrest post-stroke neuronal damage. The patient is monitored for recovery signs. Improvement in her speech pattern is noted over the next 30 days as is increased muscle tone on the left side and muscle recovery strength and usage of her effected limbs.

example 3

TBI Patient

[0071]A 17 year old high school football player is rushed to the emergency room of a local hospital suffering from a severe concussion following a helmet to helmet impact with an opposing player. The patient is initially unconscious on the field for over 20 min. EMS personnel arrived to find the patient responding to stimuli, but completely disoriented and unable to coordinate muscle movement, articulate speech or focus eye movements. Upon arriving at the ER, the patient is administered an i.v. containing R(7)C-s-s-C peptide at 0.05 mg / kg. Delivery of the peptide continued until brain swelling resulting from the impact returns to normal state (3-5 days). Without being bound by any particular theory, the therapeutic is to arrest neuronal cell death resulting from these documented post-traumatic effects. Monitoring the patient though this period (and beyond) shows that he remains symptom free of TBI and post-concussion effects (i.e. avoiding short-term memory loss or exhibi...

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Abstract

A therapeutic composition for treating brain injury comprising a polyarginine peptide of from 5 to 9 arginines, and further comprising 1 or more terminal cysteines. The composition is administered in therapeutically effective dosages prophylactic ally as soon as possible post-injury in treating neuronal injury.

Description

STATEMENT OF GOVERNMENTAL RIGHTS[0001]This invention was made with government support under National Institute for Neurological Disorders of the NIH Grant #:R21-NS031176 and National Eye Institute of the NIH Grant #:R01-EY014430. The government has certain rights in the invention.FIELD OF THE INVENTION[0002]The polyarginine and polyarginine / cysteine compositions disclosed here provide therapeutic options for neurological insult with particular reference to stroke, traumatic brain injury, and spinal cord injury (collectively “neuronal injury”). Specific note is made of the compositions of this invention moderating or avoiding the pathologic metabolic cascades associated with stroke, traumatic brain injury (TBI) and retinal damage as a result of glaucoma. Treatment of macular degeneration is also noted.BACKGROUND OF THE INVENTION[0003]A stroke, or cerebrovascular accident (CVA), is the rapid loss of brain function due to disturbance in the blood supply to the brain. This can be due to...

Claims

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Application Information

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IPC IPC(8): C07K7/06A61K38/08
CPCC07K7/06A61K38/00C08G69/10A61K38/08A61P25/00A61P27/02A61P27/06A61P9/10A61K9/0019
Inventor GOEBEL, DENNIS J.MARSHALL, JOHN
Owner BROWN UNIVERSITY
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