Achondroplasia
Achondroplasia is an autosomal dominant genetic disorder caused by a specific mutation in the FGFR3 gene. Protheragen is committed to providing cutting-edge diagnostic and therapeutic development solutions to address the challenges of achondroplasia management. As your reliable partner in achondroplasia therapeutic research, we provide comprehensive and high-quality services to meet all your scientific research needs.
Introduction to Achondroplasia
Achondroplasia is an autosomal dominant genetic disorder and the most common form of skeletal dysplasia, caused by a specific mutation in the FGFR3 gene. This mutation leads to abnormal endochondral ossification, resulting in characteristic disproportionate short stature with rhizomelic shortening of the limbs, macrocephaly, and midface hypoplasia. The condition is associated with significant orthopedic and neurological complications, necessitating multidisciplinary management.
Fig.1 Drug development process for achondroplasia. (Legeai-Mallet L, Savarirayan R., 2020)
Pathogenesis of Achondroplasia
Achondroplasia is primarily caused by a specific gain-of-function mutation in the FGFR3 gene (fibroblast growth factor receptor 3), overwhelmingly due to a glycine-to-arginine substitution at position 380 (p.Gly380Arg). This mutation leads to constitutive activation of the receptor, which disrupts endochondral ossification by inhibiting chondrocyte proliferation and differentiation in the growth plate, resulting in the characteristic disproportionate short stature.
Fig.2 The cellular mechanism of disease in achondroplasia. (Savarirayan R, et al., 2022)
Therapeutic Development for Achondroplasia
| Drug Name | Mechanism of Action | Targets | NCT Number | Research Phase |
| TYRA-300 | A selective FGFR3 inhibitor designed to target the root cause by blocking the overactive receptor's signaling. | FGFR3 | NCT06842355 | Phase II |
| KK8398 | A novel FGFR3 antagonist that binds to and stabilizes the inactive state of the FGFR3 receptor, normalizing its activity. | FGFR3 | NCT06926491 | Phase III |
| TransCon CNP | A long-acting prodrug that slowly releases a C-type natriuretic peptide (CNP) analog. CNP antagonizes the MAPK pathway downstream of FGFR3. | NPR-B | NCT05929807 | Phase II |
| Navepegritide | A long-acting C-type natriuretic peptide (CNP) conjugate designed to have an extended half-life, allowing for less frequent dosing. | NPR-B | NCT06732895 | Phase IIb |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
At Protheragen, we provide end-to-end therapeutic development and diagnostic solutions for rare bone diseases like achondroplasia. Our services span from disease modeling and molecular analysis to preclinical validation, leveraging advanced technologies to accelerate targeted therapy development. We specialize in creating robust, biologically relevant models that faithfully recapitulate disease mechanisms, enabling more efficient and predictive preclinical research.
Therapeutic Development Services
Disease Model Development Services
| In Vitro Model Development | |
|
|
| Animal Model Development | |
|
|
To advance the commercialization of novel therapies for achondroplasia, Protheragen provides comprehensive preclinical research services, covering pharmacodynamics (PD), pharmacokinetics (PK), and toxicology studies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Legeai-Mallet L, Savarirayan R. Novel therapeutic approaches for the treatment of achondroplasia[J]. Bone, 2020, 141: 115579.
- Savarirayan R, Ireland P, Irving M, et al. International Consensus Statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia[J]. Nature Reviews Endocrinology, 2022, 18(3): 173-189.