Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method and composition for treatment of skeletal dysplasias

a technology for skeletal dysplasia and composition, applied in the field of compositions for treating skeletal dysplasia, can solve the problems of skeletal dysplasia (sd), and achieve the effect of enhancing np stabilization in circulation and increasing stability

Inactive Publication Date: 2008-08-14
HEPACORE LTD
View PDF14 Cites 35 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0023]The present invention also provides NP variants with increased stability.
[0024]The present invention further provides a method to enhance NP stabilization in circulation.

Problems solved by technology

Moreover, mutations at various positions in this receptor result in skeletal dysplasias (SD).

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method and composition for treatment of skeletal dysplasias
  • Method and composition for treatment of skeletal dysplasias
  • Method and composition for treatment of skeletal dysplasias

Examples

Experimental program
Comparison scheme
Effect test

example 1

Ex Vivo Bone Culture

[0080]Femora derived from achondroplasia model mice (Ach369 knock-in mice carry the Gly to Cys mutation at position 369, analogous to position 375 in humans or Ach374 knock-in mice that carry the Gly to Arg mutation at position 374, analogous to position 380 in humans) were dissected from P0 wild type, heterozygote and homozygote littermates and cultured in the presence of natriuretic peptides for 15 days.

[0081]Protocol for bone culture: Femoral bone cultures were performed by excising the hind limbs of mice. The limbs were carefully cleaned from the surrounding tissue (skin and muscles) and the femora exposed. The femora were removed and further cleared from tissue remains and ligaments. The femora were measured for their initial length, using a binocular with an eyepiece micrometer ruler. The bones were grown in 1 ml of medium (α-MEM supplemented with penicillin (100 units / ml), streptomycin (0.1 mg / ml), nystatin (12.5 units / ml), BSA (0.2%), β-glycerophosphate (...

example 2

Natriuretic Peptides Lead to an Increase in the Size of Growth Plate: Morphological and Immunohistological Analysis

[0086]Most of the elongation induced by natriuretic peptides observed in bone culture results from epiphyseal growth and not from elongation of the mineralized diaphysis. Morphological analysis of the cellular composition of the growth plate in treated samples revealed that there is an increase in the size of the proliferative region and in the size of the hypertrophic zone. In addition, there is an area of acellular matrix similar to that observed in the growth plate of FGFR3 knockout mice. Therefore, there seems to be an increase in proliferation which leads to a larger growth plate.

[0087]Mouse-specific BNP was synthesized and labeled with biotin. Biotinylated BNP was tested in bone culture on bones derived from Achondroplasia mice and shown to induce bone elongation. Nevertheless, a higher concentration of BNP was needed. Histological analysis of the distribution of ...

example 4

Implantation of Alginate Encapsulated Cells that Secrete CNP

[0098]Implantation of cells expressing high levels of NPs is a further method for providing a continuous source of NPs. NIH-3T3 fibroblasts were infected with retrovirus expressing mouse CNP and selected for resistance to neomycin. CNP secretion was tested by assaying the supernatant of the cells using RIA (RadioImmune Assay) specific for CNP (Phoenix Pharmaceuticals) and following manufacturer's instructions. The cells are encapsulated in APA (alginate-polylysine-alginate) complex according to the protocol described by Chang (Chang (1997) Ann N Y Acad Sci 831:461-73) and summarized below.

[0099]Materials and Methods:

[0100]1. Cell Preparation: Cells are removed from plate with trypsin, resuspended in media, transferred to 50 cc tube, spun down 5-10 minutes 100 rpm, media removed.

[0101]2. PBS Wash: Cells are resuspended in PBS, spun 5-10 minutes at 1000 rpm, PBS removed and cells resuspended in 0.5 ml PBS.

[0102]3. Alginate: M...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
concentrationsaaaaaaaaaa
lengthaaaaaaaaaa
volumeaaaaaaaaaa
Login to View More

Abstract

The present invention discloses pharmaceutical compositions for the treatment of skeletal dysplasias, comprising as an active ingredient at least one natriuretic peptide. Unexpectedly, it has been shown that the natriuretic factors may be effective for bone elongation in situations of abnormal bone growth especially for achondroplasia. The effects of the natriuretic peptide may be further enhanced by prolonging its residence time or action at the target site.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a division of U.S. application Ser. No. 10 / 664,605 filed Sep. 15, 2003, which is a continuation of the U.S. national phase of International application PCT / IL02 / 00229 filed Mar. 20, 2002, which claims the benefit of U.S. application No. 60 / 276,939 filed Mar. 20, 2001. The content of each prior application is expressly incorporated herein by reference thereto.FIELD OF THE INVENTION[0002]The present invention relates to compositions for treatment of skeletal dysplasias, such as achondroplasia, and in particular to pharmaceutical compositions for bone elongation in disorders related to abnormal bone growth comprising natriuretic peptides or natriuretic factors.BACKGROUND OF THE INVENTION[0003]Bone Development[0004]Endochondral ossification is a fundamental mechanism for bone formation, whereby cartilage is replaced by bone. Endochondral ossification requires the sequential formation and degradation of cartilaginous struct...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/216A61K31/195A61P19/00A61P19/08A61KA61K35/12A61K38/00A61K38/22A61K48/00C07K14/58C07K14/61
CPCA61K35/12A61K38/2242A61K48/00A61K35/33C07K14/58C07K14/61C07K2319/02A61K2035/128A61P19/00A61P19/08
Inventor GOLEMBO, MYRIAMYAYON, AVNER
Owner HEPACORE LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com