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Treatment of conditions involving dopaminergic neuronal degeneration using NOGO receptor antagonists

A dopaminergic, neuronal technology with applications in neurobiology and pharmacology

Inactive Publication Date: 2007-04-11
BIOGEN MA INC +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these treatment options are still in the early stages of development

Method used

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  • Treatment of conditions involving dopaminergic neuronal degeneration using NOGO receptor antagonists
  • Treatment of conditions involving dopaminergic neuronal degeneration using NOGO receptor antagonists
  • Treatment of conditions involving dopaminergic neuronal degeneration using NOGO receptor antagonists

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Example 1: Soluble Nogo receptor (310)-Fc attenuates turning behavior and increases striatal dopamine levels after 6-hydroxydopamine lesion in rats

[0071]Male Sprague-Dawley rats (150-200 g, Charles River) were anesthetized with isoflurane and placed in a stereotaxic frame. Wipe the surgical site with povidone-iodine and ethanol and make a 1-inch midline sagittal incision to expose bregma. Make a small gouge in the skull above the injection site and place 20 μg of 6-hydroxydopamine hydrochloride (6-OHDA) in 2 μl (saline / 0.2% ascorbate) at coordinates AP+0.7, 2.8 mm lateral to the midline , Stereoscopic infusion into the left striatum at DV-5.5mm on the ventral surface of the skull. 6-OHDA was infused into a 29 gauge stainless steel cannula at a rate of 0.5 μl / min over 4 min using a syringe pump attached to polyethylene tubing. After infusion of 6-OHDA, the cannula was left in place for an additional 2 min and then withdrawn slowly. A 5 mm long alzet brain infusion ...

Embodiment 2

[0074] Example 2: Reduced turning behavior in response to apomorphine stimulation in NgR-null mice following 6-OHDA lesion of the striatum

[0075] Male or female Nogo receptor knockout mouse heterozygous and wild-type littermates (15-30 g) were anesthetized with ketamine and xylazine (100 and 10 mg / kg ip, respectively) and placed in a stereotaxic frame. The surgical site was swabbed with betadine and ethanol and a 0.5 cm midline sagittal incision was made to expose bregma. Make a small gouge in the skull above the injection site and place 10 μg of 6-hydroxydopamine hydrochloride (6-OHDA) in 1 μl (saline / 0.2% ascorbate) at coordinates AP+0.7, 2.8 mm lateral to the midline , Stereoscopic infusion into the left striatum at DV5.5mm on the ventral surface of the skull. 6-OHDA was infused into a 29 gauge stainless steel cannula at a rate of 0.5 μl / min over 2 min using a syringe pump attached to polyethylene tubing. After infusion of 6-OHDA, the cannula was left in place for an ad...

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Abstract

The invention provides methods for promoting regeneration or survival of dopaminergic neurons in a mammal displaying signs or symptoms of dopaminergic neuronal degeneration, including a human with Parkinson's disease, using Nogo receptor antagonists.

Description

field of invention [0001] The present invention relates to neurobiology and pharmacology. More specifically, it relates to the treatment of diseases involving the degeneration of dopaminergic neurons by administering Nogo receptor-1 antagonists. Background of the invention [0002] Certain neurodegenerative disorders are characterized by the degeneration of dopamine neurons. For example, Parkinson's disease is associated with progressive destruction of dopamine neurons in the substantia nigra of the midbrain. This disruption leads to lowered levels of the chemical transmitter dopamine. Physical symptoms of Parkinson's disease include impairment of voluntary movement and uncontrollable rhythmic twitches of muscle groups that produce the characteristic tremors. [0003] The most widely used treatment for Parkinson's disease is the administration of the dopamine precursor, levodopa (L-3,4-dihydroxyphenylalanine), which acts indirectly by replacing lost dopamine. However, th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17C07K16/28A61P25/00A61P25/28C07K14/47
CPCC07K14/4703C07K16/28A61K38/1787A61P25/00A61P25/14A61P25/16A61P25/28A61P43/00A61K38/17
Inventor 简·K·雷尔顿托马斯·M·恩格伯斯蒂芬·M·斯特里特马特
Owner BIOGEN MA INC