Achondroplasia
Achondroplasia is a rare genetic disease characterized by a myriad of skeletal comorbidities that result from aberrant endochondral ossification in the long bones and axial skeleton. Our company has a cutting-edge research and therapeutic innovation ability, which can support all-round service for your research.
Overview of Achondroplasia
Achondroplasia is a genetic disorder with a global prevalence of 4.73 cases per 100000 individuals, and the disruptive mutation in the fibroblast growth factor receptor 3 (FGFR3) gene, a pivotal regulator of bone growth, causes the pathogenesis of this condition. This mutation leads to abnormal growth of cartilage and bone, resulting in short limbs and other characteristic features of the condition.
Fig.1 Current and potential therapeutics for achondroplasia. (Wrobel, W., et al., 2021)Pathogenesis of Achondroplasia
The pathogenesis of achondroplasia involves an abnormality in the process of bone growth and development. The mutant FGFR3 gene engenders an over-activation of the FGFR3 protein, which, in turn, inhibits bone tissue growth. Consequently, the bones in the limbs and other body regions undergo aberrant shortening, manifesting as the characteristic skeletal abnormalities associated with the disorder. FGFR3 signaling can lead to the occurrence of achondroplasia by activating several molecules.
- ERK1/2
- MEK1/2
- RAS
- RAF-1
- STAT1
- P38
Diagnostics Development of Achondroplasia
The application of advanced genetic testing techniques emerges as a vital tool for achondroplasia. Utilizing cutting-edge methodologies such as polymerase chain reaction (PCR) and direct DNA sequencing facilitates the identification of specific FGFR3 gene mutations associated with the disorder, which can pinpoint the underlying genetic aberrations driving the manifestation of achondroplasia.
Therapeutics of Achondroplasia
Small Molecule Drugs Therapy
Tyrosine kinase inhibitors such as infigratinib and FGFR inhibitors like ASP5878 hold the potential to mitigate the deleterious effects of abnormal bone growth by modulating FGFR3 activity. Furthermore, novel therapies such as CNP analogs (vosoritide) and derivatives (TransCon CNP) are beneficial for bone therapy.
Aptamer Therapy
Innovative approaches such as the FGF2-targeted aptamer RBM-007 have demonstrated efficacy in blocking the destructive effects of the FGFR3 receptor, thereby preserving the integrity of the epiphyseal growth plate and promoting bone health in individuals afflicted with the disorder.
Our Services
Our company stands at the vanguard of rare disease research, equipped with state-of-the-art technology and a team of seasoned experts. We can offer animal models and therapeutic development platforms to advance the frontiers of achondroplasia research.
Platforms of Achondroplasia Therapy Development
Animal Models of Achondroplasia
Animal models play a crucial role in understanding disease mechanisms and testing potential therapeutics. In the case of achondroplasia, our company can provide several animal models to mimic the disease and develop potential therapeutics for the condition.
| 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 | |
With our comprehensive services and unwavering commitment to scientific excellence, we can support your pharmacokinetics analysis and drug safety evaluation, to help you make significant strides in the understanding and therapeutic 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.