Cryptophthalmos, syndactyly, and genitourinary stadiums, frequently associated with kidney agenesis or dysplasia, are some of the developmental abnormalities of Fraser syndrome, a rare genetic disorder. Protheragen offers comprehensive preclinical drug and therapy development services tailored to address the specific challenges of Fraser syndrome.
Introduction to Fraser Syndrome
The estimated incidence of Fraser syndrome, a rare autosomal recessive genetic disorder, stands at approximately 1 in 200,000 live births and potentially higher in stillbirths. The disorder is marked by a specific pattern of malformations that affect multiple organ systems. Other key characteristics include partial or complete eyelid fusion, skin fusion among fingers and toes, and significant anomalies of the genitourinary tract which frequently manifests as unilateral or bilateral renal agenesis.
Pathogenesis of Fraser Syndrome
Deficiency in structural components such as the Fraser protein complex which is fundamental for an embryonic basement membrane integrity, leads to poor epithelial-mesenchymal interactions and the manifestation of the Syndrome. Located on the fourth chromosome, the genes which causes the syndrome are to blame for impaired organizational structure of basement membranes in the skin, kidneys, and developing respiratory systems of the fetus. Symptoms resulting from these effects include cryptophthalmos, syndactyly, and renal agenesis.
Fig.1 Schematic of FREM2 protein structure and compound heterozygous FREM2 variants. (Ikeda, S.,
et al., 2020)
Therapeutic Development for Fraser Syndrome
| Drug Name |
Therapeutic Target/Mechanism of Action |
Relevant Clinical Manifestations |
Validated Tools/Technology Platforms |
Development Stage |
| PMO-based Exon Skipping Oligonucleotide |
Antisense oligonucleotides (AONs) to skip pathogenic exons and restore partial FRAS1 protein expression. |
Splice-site mutation subtypes |
Phosphorodiamidate morpholino oligomers (PMO; e.g., Eteplirsen for DMD) |
Preclinical Exploration |
| Galunisertib (LY2157299) |
TGF-β receptor 1 inhibitor to suppress fibrosis and organ damage. |
Renal fibrosis, pulmonary hypoplasia |
TGF-βR1 inhibitor (Phase II completed in idiopathic pulmonary fibrosis) |
Cross-disease Repurposing (Phase II Data) |
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 develops advanced
disease models for Fraser syndrome as well as offers
therapeutic development services. For FRAS1/FREM2/GRIP1 signaling pathway modulation and basement membrane integrity restoration, along with renal agenesis and multisystem developmental anomalies.
Therapeutic Development Platform for Fraser Syndrome
Protheragen combines deep expertise in developmental biology with advanced molecular profiling technologies to address FRAS1/FREM2/GRIP1-linked mechanisms in Fraser syndrome. Our team delivers tailored solutions—from target identification to lead optimization—powered by cutting-edge organoid systems and proprietary high-throughput screening platforms.
Disease Models Development for Fraser Syndrome
Protheragen offers innovative and comprehensive
disease models advance the preclinical research of the familial kidney stone disease. Our platform integrates
cell-based models,
kidney organoids, and
animal models to capture the genetic and metabolic signatures of familial kidney stone disease and support extensive drug discovery and mechanism- based investigations.
Cell-based & Organoid Models
- Renal Epithelial Cells
- Fibroblast Lines
- 3D Co-Culture Systems
- Kidney Organoids
- Multi-Organoid Chips
Animal Models Development
- Fras1 Knockout Mice
- Frem2 Knockout Mice
- Transgenic Tg(fras1:EGFP) lines
- Tissue-specific GRIP1 KO mice
- Fras1/ Frem2 Morphants
Protheragen integrated preclinical development solutions specifically designed for research in kidney diseases. We specialize in
disease model development,
pharmacokinetics, and
drug safety evaluation, enabling us to support your investigation from the initial stages to preclinical validation. If you are interested in our services, please don't hesitate to
contact us.
References
- Ikeda, S., et al. "Prenatal Diagnosis of Fraser Syndrome Caused by Novel Variants of Frem2." Hum Genome Var 7 (2020): 32.
- Turgut, G. T., et al. "Frem2-Related Fraser Syndrome with Popliteal Pterygium and Structural Central Nervous System Anomalies." Eur J Med Genet 66.3 (2023): 104712. Print.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
