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Use of TrkB antibodies for the treatment of respiratory disorders

A technology for respiratory diseases and antibodies, applied in respiratory diseases, antibodies, anti-animal/human immunoglobulins, etc., can solve the problem of no effective treatment for diseases

Inactive Publication Date: 2010-12-08
NOVARTIS AG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

To date there is no effective treatment for the disease

Method used

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  • Use of TrkB antibodies for the treatment of respiratory disorders
  • Use of TrkB antibodies for the treatment of respiratory disorders
  • Use of TrkB antibodies for the treatment of respiratory disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0247] Example 1: Administration of TrkB agonist antibody (C20) to Mecp2 mice

[0248] TrkB agonist antibody (C20) or saline was administered intraperitoneally to Mecp2-KO and wild-type males aged 4 (early symptoms) to 8 weeks (late symptoms) at a dose of 3 mg / kg body weight twice weekly for animals Test for 6 to 8 weeks. 9-14 mice per group were tested for a total of four groups (wild type administered saline, wild type administered mAb, knockout animals administered saline and knockout animals administered mAb). Mecp2 knockout mice were purchased from Jackson Labs (strain Mecp2 tm1.1Bird / J(#003890)).

[0249] like Figure 1A As shown, mice exhibited decreased body weight when administered TrkB agonist mAb. The topmost line (white squares show data points) represents saline administered Mecp2 wild type mice. The second top line (black squares show data points) represents Mecp2 wild-type mice administered TrkB agonist antibody. The second bottom line (white circles sh...

Embodiment 2

[0256] Example 2: Administration of TrkB agonist antibody (C20) to Mecp2 mice

[0257] To test for apnea, whole body plethysmography can be performed using a system designed by Buxco Research Systems. Conscious, unrestrained mice were placed in a plethysmographic chamber (vertical Plexiglas cylinder, 4 inches in diameter and 5 inches in height). Maintain air flow to ensure a constant exchange of fresh air into the cavity, providing food, bedding and water. To accurately assess the frequency of apneas, mice need to acclimate to the plethysmographic chamber. Airway response recordings were performed at various intervals once they were fully acclimated, without removing the animals from the chamber. The acclimatization and recording periods should not exceed 2 h; therefore, mice will be in the chamber for no more than two hours at a time.

[0258] In the same mice, plethysmographic recordings were performed no more than twice a week. Once the plethysmographic recordings were ...

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PUM

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Abstract

The application discloses TrkB antibodies for the development of new therapeutics to treat, prevent or ameliorate respiratory disorders. The application also relates to methods to treat, prevent or ameliorate said conditions and pharmaceutical compositions therefor, as well as to a method to identify compounds with therapeutic usefulness to treat conditions associated with respiratory disorders.

Description

Background of the invention [0001] Tyrosine kinase receptor B (TrkB) belongs to a family of single transmembrane receptor tyrosine kinases that also includes TrkA and TrkC. These tyrosine kinase receptors (trks) mediate the activity of neurotrophins. Neurotrophins are required for the survival and development of neurons and regulate synaptic transmission by modulating neuronal structure and synaptic plasticity. Neurotrophins include, but are not limited to: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 / 5 (NT-4 / 5) ( Lo, KY et al., (2005) J. Biol. Chem. , 280:41744-52). [0002] TrkB is a high-affinity receptor for BDNF (Minichiello, et al., Neuron 21:335-45 (1998)), which is highly expressed in the brain, especially in the neocortex, hippocampus, striatum and brainstem; Isoforms have also been found in muscle tissue. Neurotrophin binds to trk, activates the receptor, dimerizes and autophosphorylates specific ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P11/00C07K16/28
CPCC07K16/2863C07K2316/95A61K2039/505C07K2317/75A61P11/00A61P11/16A61P43/00
Inventor C·布劳斯坦
Owner NOVARTIS AG
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