Noonan Syndrome
Noonan syndrome is an autosomal dominant disorder that is phenotypically highly variable and characterized by facial dysmorphism, short stature, congenital heart defect, and developmental delay with different degrees. Protheragen is a premier service provider for such research including rare cardiovascular diseases, which include Noonan syndrome. We specialize in every phase of medical product development from novel diagnostics to targeted therapeutics and their corresponding disease models.
Introduction to Noonan Syndrome
Noonan syndrome is an autosomal-dominant inherited disorder with a highly variable phenotype that may affect multiple organ systems throughout the individual's lifetime, occurring at an incidence of 1:1000 to 1:2500 live births. The cardinal features are dysmorphic face, short stature, and cardiac anomalies. Fifty to eighty percent of people have a congenital heart disease. This is, however, a highly variable condition that picturizes genetic heterogeneity.
Fig.1 Features of Noonan syndrome. (Zenker, M., et al., 2022)Pathogenesis of Noonan Syndrome
Noonan syndrome is inherited as an autosomal dominant trait and is genetically heterogeneous. To date, mutations in nine genes (PTPN11, SOS1, KRAS, NRAS, RAF1, BRAF, SHOC2, MEK1, and CBL) have been described to cause disease as well as related phenotypes. These include genes that produce components or controls of the RAS/mitogen-activated protein kinase (MAPK) signaling cascade, and which are essential for many cellular activities including proliferation, survival, differentiation, and metabolism.
Fig.2 RAS-MAPK signal pathway including the mutations related to Noonan syndrome. (Zenker, M., et al., 2022)Therapeutics Development for Noonan Syndrome
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| Trametinib | Trametinib selectively binds to and inhibits MEK1/2 so that the activation of ERK1/2 is attenuated. | MEK | NCT06555237 | Phase II |
| Somapacitan | Acts by binding to growth hormone receptor which intensifies sustained IGF-1 production and metabolic effects in Noonan syndrome individuals. | GHR | NCT05723835 | Phase III |
| MEK162 | A MEK inhibitor is active in Noonan syndrome by inhibiting the hyperactive RAS/MAPK pathway. | MEK | NCT01556568 | Phase II |
| rhIGF-1/rhIGFBP-3 | Raises IGF-1 levels, which in turn counteracts inadequate growth hormone signaling to ensure normal growth and metabolism. | / | NCT00351221 | Phase II |
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
Committed to quality and efficiency, we expedite discovery to scale the development of groundbreaking therapeutics. We work with our clients to develop custom-made research plans that involve the use of the latest methodologies. From novel diagnostic and targeted therapeutic to designing and disease model development, our experienced team will ensure you have a solution for the unique requirements of these complex diseases.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for Noonan Syndrome
The utility of animal models in studying the pathophysiology of Noonan syndrome and testing potential therapeutic applications is emphasized. We have customized animal model development services, employing cutting-edge methods that closely recapitulate the characteristics of Noonan syndrome so that researchers have the best available tool for an extensive drug screen and therapeutic test.
Genetically Engineered Animal Models
An animal model of Noonan syndrome is formed by gene editing or transgenic techniques to introduce specific mutations in these important genes (PTPN11, RAF1, KRAS, etc.), and to establish the phenotypes observed in individuals.
- Ptpn11 mutation model
- Sos1 mutation model
- Shoc2 mutation model
- Raf1L613V model
- K-RasV14I model
- Other models
In addition to our expertise in therapy and animal model development, Protheragen offers full-service preclinical services, focusing on pharmacokinetics studies and general drug safety testing. Collaborate with us and benefit from a rich resource of cross-disciplinary knowledge in this very demanding field from concept to realization. If you have any interest in our services, please feel free to contact us.
Reference
- Zenker, Martin et al. "Noonan syndrome: improving recognition and diagnosis." Archives of disease in childhood 107.12 (2022): 1073-1078.
For research use only, not for clinical use.