Oral-Facial-Digital Syndrome Type 1 (OFD1) is a rare disorder with an estimated prevalence of 1 in 250,000 live births. It is an x-linked genetically transmitted disorder, with a marked neurodevelopmental impact characterized by profound structural anomalies, which can be traced back to single mutations in the OFD1 gene. Protheragen offers OFD1 pathophysiology research services in the scope of drug and therapy development.
Introduction to Oral-Facial-Digital Syndrome Type 1
Oral-Facial-Digital Syndrome Type 1, which is also commonly referred to as Papillon-Léage-Psaume syndrome, represents a strikingly rare X-linked dominant neurodevelopmental disorder. It is characterized by a spectrum of anomalies that OFD1 is usually lethal to males in embryonic phases, resulting in a near-complete female population among the affected individuals. OFD1 also involves various visceral anomalies such as polycystic kidney disease (PKD), a notable and progressive condition that usually develops in later childhood or adulthood, which can lead to end-stage renal disease (ESRD). Additionally, OFD1 is classified as a ciliopathy and connects the range of the disorder to primary cilia function.
Fig.1 The biopsy specimen revealed a well-demarcated cystic lesion filled with keratinous materials in dermis. (Ritchie, Zayat and Chebib, 2023)
Pathogenesis of Oral-Facial-Digital Syndrome Type 1
Oral-Facial-Digital Syndrome Type 1 (OFD1) is a genetic disorder caused by mutations in the OFD1 gene on the X chromosome, leading to defects in primary cilia function. This disrupts cellular signaling and affects multiple systems, including the kidneys. Renal involvement is common, with polycystic kidney disease being the primary manifestation. The formation of kidney cysts is linked to abnormal ciliary signaling in kidney tubules, leading to impaired function and, in severe cases, kidney failure. Early renal monitoring is crucial for managing the disease.
Therapeutics Development for Oral-Facial-Digital Syndrome Type 1
| Drug/Technology |
Therapeutic Target |
Key Findings/Mechanism |
Development Stage |
| Purmorphamine |
Smoothened receptor (SMO) |
Activates ciliary Shh signaling; effective in other ciliopathies |
Preclinical |
| Rapamycin/ Everolimus |
mTORC1-RPTOR complex |
Suppresses cystic cell proliferation; anecdotal efficacy in case reports |
Phase II |
| Pirfenidone |
TGF-β1 ligand |
Anti-fibrotic action to delay interstitial damage |
Preclinical |
| Olaparib |
PARP1 enzyme |
Synthetic lethality targeting DNA repair defects |
Preclinical |
| ACY-1215 |
HDAC6 protein |
Restores histone acetylation and chromatin plasticity |
Preclinical |
| AAV-miniOFD1 |
OFD1 gene (isoform 1) |
Compact gene design to restore ciliary function in vivo |
Preclinical |
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 specializes in developing advanced disease models for oral-facial-digital syndrome type 1 and offers comprehensive preclinical therapeutic development services. We focus on understanding the diverse genetic and ciliary impacts that lead to OFD1.
Therapeutic Development Platforms for Oral-Facial-Digital Syndrome Type 1
Disease Models Development for Oral-Facial-Digital Syndrome Type 1
Protheragen offers innovative and comprehensive disease models to advance the preclinical research of oral-facial-digital syndrome type 1. Our platform integrates cell-based models, kidney organoids, and animal models to effectively capture the ciliary dysfunction and developmental defects that cause OFD1, supporting extensive drug discovery and mechanism-based investigations focused on organogenesis and renal pathology.
- OFD1R137X mutant renal epithelial cells
- Cilium-deficient oral mucosa organoids
- Cerebellar spheroids with OFD1 knockdown
- 3D bioprinted kidney-cyst co-cultures
- Ofd1flox; Ksp-Cre mice (renal-specific KO)
- Ofd1+/- heterozygous female mice
- ofd1tp39b zebrafish
- OFD1Y291C knock-in rats
- Human renal cystoids in FRGS mice
Drug Pharmacokinetics & Safety Evaluation Services
In Vitro ADME Services
- Renal Clearance Assay
- Drug-Transporter Interaction Screening
- Metabolic Stability Assay
- CYP Inhibition Screening
- Plasma Protein Binding
Protheragen provides integrated preclinical development solutions specifically designed for research in disorders like oral-facial-digital syndrome type 1. We specialize in disease model development, pharmacokinetics, and drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation.
Contact us today to accelerate your oral-facial-digital syndrome type 1 research with end-to-end solutions.
References
- Ko, Y. W., et al. "Oral-Facial-Digital Syndrome Type 1: A Case Report and Review." Ann Dermatol 34.2 (2022): 132-35.
- Ritchie, L., R. Zayat, and F. T. Chebib. "Oral-Facial-Digital Syndrome Type 1: The Kidney Cystic Disease That Mimics Autosomal Dominant Polycystic Kidney Disease." Kidney Int 104.2 (2023): 399. Print.
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