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Neural regeneration peptides and methods for their use in treatment of brain damage

a neuronal regeneration and neuropeptide technology, applied in the direction of peptide sources, bacteria, fungi, etc., can solve the problems of significant neuronal cell loss and loss of brain function, no treatment available to restore neuronal function, and no treatment currently available to prevent cell death in the brain, etc., to achieve high identity, increase neuronal proliferation and migration, and induce migration, proliferation and/or neurite outgrowth

Inactive Publication Date: 2011-12-15
CURONZ HLDG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides new approaches to the treatment of brain injuries and diseases by administering specific peptides, called neural regeneration peptides (NRPs), to promote the growth and regeneration of neurons in damaged areas of the brain. These NRPs can be administered alone or in combination with other NRPs or other types of agents to promote neural outgrowth, migration, and survival. The NRPs can have various amino acid sequences and molecular weights, and can have one or more domains that enhance their biological activity. The invention also provides methods of treatment for brain injuries and diseases by administering NRPs to promote neuronal or neuroblast migration, proliferation, survival, and / or neurite outgrowth."

Problems solved by technology

Moderate to severe traumatic brain injury (TBI), and focal or global ischemia can result in significant neuronal cell loss and loss of brain function within a short time period after the insult.
There are no treatments currently available to prevent cell death that occurs in the brain as a consequence of head injury or damage caused by disease.
To date, there is also no treatment available to restore neuronal function.
No drugs are currently available to intervene in the disease process or prevent cell death.

Method used

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  • Neural regeneration peptides and methods for their use in treatment of brain damage
  • Neural regeneration peptides and methods for their use in treatment of brain damage
  • Neural regeneration peptides and methods for their use in treatment of brain damage

Examples

Experimental program
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Effect test

example 1

Identification of Human and Mouse NRPs

[0142]Using bioinformatic tools, we identified NRPs within the human and mouse genome. These new NRP genes were annotated using the following methods.

[0143]We performed a BLASTP search using the 16 amino acid rat NRP-1 as a template. We found a sequence having 100% identity to the rat NRP-1 sequence: a human cachexia-related protein. The cDNA of the human cachexia-related protein is encoded by 5 exons located on human chromosome 12. Because of the identity of the rat NRP-1 and a portion of the human cachexia protein, a new annotation of NRP orthologs was orientated alongside these 5 exons. tBlastN searches within the human NCBI-database revealed a previously unknown open reading frame (ORF) of 321 nucleic acids on chromosome 13. This sequence encodes a peptide having striking homology to the cachexia-related protein fragment having amino acids 1-30 (cachexia protein without signal sequence). These methods were also used to identify other human N...

example 2

In Vitro Assay for Evaluating Migration-Inducing Activity I

[0147]We developed a new assay system for identifying NRP having migration-inducing activity. The assay system was used following guidelines approved by the Gesundheitsamt Magdeburg animal ethics committee. Newborn Long Evans rats (P0) were killed by decapitation, and neural tissues were used for preparation of organotypic cultures (OTCs). Neocortical tissue (areas 17-18 according to the Paxinos rat atlas of the developing rat brain) and thalamic tissue from the dorsal thalamus (visual areas) were extracted. These areas represent the visual axis. The dorsal thalamus was accessed by an intersection cut to remove the hypothalamus. Subsequently, the thalamus was sliced frontally using a McIllwain tissue chopper into 350 μm thick slices. Using a dissecting microscope, the habenula nucleus served as a landmark to select only dorsal thalamic areas. Cortical tissues were cut using two sagittal and two frontal intersections in order...

example 3

Migrating Cells are of Neuronal Origin and Adopt a Differentiated Phenotype

[0155]To determine the cellular nature of cell bridges, we used neural-specific immunohistochemistry. Immunohistochemistry was carried out according to methods of (Obst and Wahle, 1995). OTCs as described above were rinsed twice in 0.1 M phosphate buffer for 3 h. After a study was carried out, tissues were fixed using conventional fixatives suitable for immunohistochemistry. To improve antibody penetration into the tissues and cells, OTCs were incubated for 10 min in a freezing solution consisting of 25% sucrose; 10% glycerol; 100 mM NaCl in 0.01 M phosphate buffer (pH 7.4) at −80° C. (Gúlyas et al., 1996). OTCs were then incubated for 5 min in 1% H2O2 followed by a treatment of 0.4% Triton 100 and 10% normal goat serum (blocking solution) for 3 h (Sigma chemicals). Primary antibodies (anti-parvalbumin IgG; anti-calretinin IgG; anti-MAP-2 IgG) were incubated with 0.4% Triton; 2% BSA; 2% normal goat serum in P...

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Abstract

The invention discloses a family of neuronal migration-inducing, proliferation-promoting and neurite outgrowth promoting factors, termed NRP compounds, and provides compositions and methods for the use of NRP compounds in the treatment of brain injury and neurodegenerative disease. NRP-1 compounds induce neurons and neuroblasts to proliferate and migrate into areas of damage caused by acute brain injury or chronic neurodegenerative disease, such as stroke, trauma, nervous system infections, demyelinating diseases, dementias, and metabolic disorders. NRP compounds may be administered directly to a subject or to a subject's cells by a variety of means including orally, intraperitoneally, intravascularly, and directly into the nervous system of a patient.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the priority under 35 USC 119(e) to U.S. Provisional Application Ser. No. 60 / 314,952, filed Aug. 24, 2001, which is incorporated into this application fully by reference. This application is also related to U.S. Utility patent application titled “Assay Methods for Neuroregeneration Peptides,” Frank Sieg and Paul Hughes, inventors, Attorney Docket No: NRNZ 1023 US2, incorporated herein fully by reference.BACKGROUND[0002]1. Field of the Invention[0003]This invention is directed to compositions and methods for the use of peptides that promote neuronal migration, proliferation, survival and / or neurite outgrowth. More specifically, this invention is directed to the use of such peptides in the treatment of brain injury and neurodegenerative disease.[0004]2. Related Art[0005]Moderate to severe traumatic brain injury (TBI), and focal or global ischemia can result in significant neuronal cell loss and loss of brain function...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/02C07K7/08C07K14/47C07K14/05C07K7/06C07H21/04C07K14/35C12N5/0793C12N15/63C12N1/00C12N5/10A61P25/28C12Q1/02G01N33/566A61P25/00A61P25/16C07K2/00C12N15/09A61K38/00A61P9/10A61P25/14C07K14/475C12N1/15C12N1/19C12N1/21
CPCC07K14/4756A61K38/00A61P9/10A61P25/00A61P25/14A61P25/16A61P25/28
Inventor SIEG, FRANKHUGHES, PAUL
Owner CURONZ HLDG
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