Achondroplasia
Achondroplasia is an uncommon genetic condition intricately linked to multiple skeletal abnormalities stemming from defective endochondral ossification within the long bones and axial skeleton. Our company possesses state of the art research and development therapeutic innovation capabilities which can provide all round service for your research endeavours.
Overview of Achondroplasia
Achondroplasia is a genetic disorder with an astonishing worldwide prevalence of 4.73 cases for every 100,000 individuals, with a particular disruptive mutation in the fibroblast growth factor receptor III (FGFR3) gene, an important regulator of bone growth. The pathogenesis of this condition stems from. As a result of this mutation, there is abnormal growth of cartilage and, thus, bone which leads to short limbs along with a multitude of other features of this condition.
Fig.1 Current and potential therapeutics for achondroplasia. (Wrobel, W., et al., 2021)Pathogenesis of Achondroplasia
The skeletal abnormalities achondroplasia is characterized by are associated with the disorder arises because of an irregularity concerning the growth and development of bone tissues. Mutant FGFR3 gene leads to increased synthesis of FGFR3 proteins that blocks bone formation due to excessive secretion of FGFR3 proteins tested in cell culture models. As a result, the bones mainly in the limbs and other regions of the body tend to shorten abnormally giving rise to skeletal deformities. The signaling of FGFR3 can be remarkably active with respect of the development of achondroplasia by a range of different molecules.
- ERK1/2
- MEK1/2
- RAS
- RAF-1
- STAT1
- P38
Diagnostics Development of Achondroplasia
The application of modern genetic testing techniques is a valuable tool for achondroplasia. Approaches like polymerase chain reaction (PCR) and direct DNA sequencing provide the means to detect specific mutations within the FGFR3 gene, thereby explaining the specific genetic alterations responsible for the development of achondroplasia.
Therapeutics of Achondroplasia
Small Molecule Drugs Therapy
Infigratinib, as well as the tyrosine kinase inhibitors, and ASP5878, as well as the FGFR inhibitors, are able to modify the harmful effects of abnormal bone growth through the modulation of FGFR3 activity. Additionally, bone therapies are helpful CNP analogs (vosoritide) and its derivative TransCon CNP.
Aptamer Therapy
An example of a novel approach FGF2 targeted aptamer RBM-007 has provided proof of concept by surrounding the degenerative effects of the FGFR3 receptor to preserve the growth plate epiphysis and promote healthy bones in people with this condition.
Our Services
Our company is a leader in the study of rare diseases and achieves unparalleled results aided by top of the line equipment and a staff full of veterans in the field. We have the capacity to provide translational research animal models and therapeutic development platforms for the achondroplasia researches.
Platforms of Achondroplasia Therapy Development
Animal Models of Achondroplasia
Understanding disease mechanisms and testing possible therapeutics are essential processes that are facilitated by animal models. These company can provide several animal models for testing for achondroplasia.
| Chemical-induced Models | ||
| Chemical drugs that can cause chondrodysplasia in animal models include retinoic acid and thalidomide. They can interfere with the normal growth and development of bones, leading to skeletal abnormalities. | ||
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| Genetically Engineered Models | ||
| The specific mutation in the FGFR3 gene of animals is associated with achondroplasia, to develop features similar to those seen in affected individuals. These animal models display similar skeletal abnormalities and growth impairment seen in humans with achondroplasia. | ||
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| Optional Species | Mice, Rats, Zebrafish, Non-Human Primates, Others | |
Through our vast array of services, we remain steadfast in our enduring pledge to scientific goal, this places us in a perfect position to assist you with pharmacokinetics analysis and drug safety evaluation. We will help you make significant advances in the comprehension and treatment of the genetic disorder. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Wrobel, Wiktoria et al. "Advantages and disadvantages of different treatment methods in achondroplasia: a review." International journal of molecular sciences 22.11 (2021): 5573.
- Legeai-Mallet, Laurence, and Ravi Savarirayan. "Novel therapeutic approaches for the treatment of achondroplasia." Bone 141 (2020): 115579.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.