Cranioectodermal Dysplasia (CED)

Cranioectodermal Dysplasia (CED), or sensenbrenner syndrome, is an ultra-rare autosomal recessive ciliopathy characterized by craniofacial, skeletal, and ectodermal anomalies alongside progressive renal disease. Protheragen delivers end-to-end preclinical development services to accelerate CED-specific therapeutic innovation.

Overview of Cranioectodermal Dysplasia

Cranioectodermal Dysplasia (CED), also known as sensenbrenner syndrome, is an ultra-rare autosomal recessive ciliopathy. It is characterized by a distinctive combination of skeletal abnormalities (e.g., short stature, narrow thorax), ectodermal features (including sparse, fine hair, dental anomalies, and nail dystrophy), and craniofacial dysmorphism (such as dolichocephaly and frontal bossing). A critical and often life-limiting component of CED is the progressive renal disease, typically presenting as nephronophthisis-like kidney disease, which can lead to end-stage renal failure in childhood or adolescence. The extreme rarity of CED underscores the urgent need for specialized research and therapeutic development.

Pathogenesis of Cranioectodermal Dysplasia

CED is primarily caused by biallelic mutations in genes that encode components of the intraflagellar transport (IFT) complex, which is essential for the formation and function of primary cilia. Key genes implicated include IFT122, WDR19, WDR35, IFT43, and IFT140. Primary cilia are crucial, highly conserved organelles that project from the surface of most eukaryotic cells, acting as cellular antennae to sense and transduce extracellular signals vital for development, homeostasis, and tissue maintenance.

Fig.1 Schematic of the localization of genotypes associated with CILK1-related phenotypes on the transcript and protein. (Sezer et al., 2025)

When mutations occur in these IFT genes, the assembly, maintenance, or function of primary cilia is disrupted. This ciliary dysfunction leads to impaired cellular signaling across multiple organ systems. In the kidney, defective cilia in renal tubular epithelial cells result in abnormal cell proliferation, cyst formation, interstitial fibrosis, and ultimately, the progressive loss of nephron function characteristic of nephronophthisis. The systemic nature of ciliary dysfunction explains the multi-organ involvement observed in CED.

Therapeutics Development for Cranioectodermal Dysplasia

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

Protheragen is a dedicated provider of preclinical research services focused on therapeutic development for cranioectodermal dysplasia. We leverage advanced disease models that capture the multi-systemic nature of CED, including its severe renal manifestations, to facilitate mechanism-based drug discovery for this complex ciliopathy.

Therapeutic Development Platforms for Cranioectodermal Dysplasia

• Small Molecule Drug
• Cell Therapy
• Gene Therapy

• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Disease Models Development for Cranioectodermal Dysplasia

Protheragen provides specialized disease models to accelerate preclinical research on cranioectodermal dysplasia. Our platform integrates advanced cell-based models, kidney organoids, and animal models. These models are meticulously developed and characterized using multi-omics profiling and functional validation to support robust target identification and comprehensive therapeutic efficacy testing for CED-specific pathways.

Cell-based & Organoid Models

• Patient-derived iPSCs
• IFT gene mutant cell lines
• iPSC-based kidney organoids
• IFT gene mutant kidney organoids

Animal Models

• Ift122^−/− zebrafish
• Wdr35 conditional knockout mice
• Ift140 mutant Xenopus
• Humanized IFT-A transgenic rat models

Drug Pharmacokinetics & Safety Evaluation Services

In Vitro ADME Services

• Metabolic Stability Assay
• Plasma Protein Binding
• Renal Tubular Epithelial Cell Uptake & Efflux
• Drug-Transporter Interaction Profiling
• Cellular Permeability

In Vivo Pharmacokinetics Services

• Systemic Pharmacokinetics
• Kidney Tissue Distribution and Retention
• Renal Clearance and Excretion Studies
• Urinary Metabolite Profiling
• Blood-to-Plasma Ratio

Drug Safety Evaluation

• General Toxicology Evaluation
• Genetic Toxicology Evaluation
• Developmental and Reproductive Toxicity Evaluation

• Immunogenicity and Immunotoxicity Evaluation
• Local Toxicity Evaluation
• Phototoxicity Evaluation

• Tissue Cross-Reactivity Evaluation
• Safety Pharmacology Evaluation
• Toxicokinetic Evaluation

Protheragen offers comprehensive, end-to-end preclinical development services specifically designed to address the unique challenges of cranioectodermal dysplasia. Our expertise spans disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your therapeutic investigations from initial target identification through to preclinical validation. We are committed to accelerating the journey of novel therapies for rare kidney diseases like CED.

If you are interested in our specialized services, please do not hesitate to contact us.

References

1. Getwan, M., et al. "Ttc30a Affects Tubulin Modifications in a Model for Ciliary Chondrodysplasia with Polycystic Kidney Disease." Proc Natl Acad Sci U S A 118.39 (2021). Print.
2. Sezer, A., et al. "A Homozygous Frameshift Variant in the Cilk1 Gene Causes Cranioectodermal Dysplasia." Eur J Hum Genet  (2025). Print.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.