Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS)

Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS) is a genetic condition resulting from PLOD1 or FKBP14 mutations, which leads to collagen biosynthesis abnormalities and connective tissue instability. Protheragen offers complete services from preclinical stage including target validation, disease modeling, and therapeutic interventions for kEDS.

Fig.1 Structural comparison between WT and M48K FKBP22. (Wiegand et al., 2023)

Introduction to Kyphoscoliotic Ehlers-Danlos Syndrome

Kyphoscoliotic Ehlers-Danlos Syndrome (kEDS) is a rare form of an autosomal recessive disorder of connective tissue characterized by profound kyphoscoliosis, joint hypermobility, congenital muscular hypotonia, and other severe skeletal manifestations. One of the rarest Ehlers-Danlos subtypes, it carries an incidence of approximately 1 in 100,000 to 200,000 live births, associated with ocular fragility and vascular complications.

Pathogenesis of Kyphoscoliotic Ehlers-Danlos Syndrome

Kyphoscoliotic Ehlers-Danlos Syndrome occurs from biallelic PLOD1 or FKBP14 mutations, disrupting collagen biosynthesis and extracellular matrix (ECM) cohesion. PLOD1 is functional defect in lysyl hydroxylase leading to low collagen crosslinking and disorganized fibril structure within skin, tendons, and blood vessels. FKBP14 mutations result in the loss of stable FKBP22 chaperone leading to impaired collagen folding and secretion which contributes to increased tissue fragility, progressive kyphoscoliosis, and multisystem connective tissue disease.

Therapeutics Development for Kyphoscoliotic Ehlers-Danlos Syndrome

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 focuses on providing comprehensive preclinical services for kEDS by therapeutic development integrating disease models for collagen instability and connective tissue pathology. Our platforms make use of precision to enhance the speed of drug discovery and the optimization of diagnostic tools.

Therapeutics Development Platforms for Kyphoscoliotic Ehlers-Danlos Syndrome

Disease Model Development for Kyphoscoliotic Ehlers-Danlos Syndrome

Protheragen designs specific kEDS pathology 2D cell models, 3D skin models, and animal models. These systems mimic the biochemical and biomechanical weakening of collagen tendons and blood vessels as well as connective tissue instability, enabling mechanistic investigations and drug testing for this uncommon disorder.

2D Cell Models & 3D Skin Models

• PLOD1-Knockout Human Dermal Fibroblasts
• FKBP14-Mutant Patient-Derived Fibroblasts
• Collagen-Deficient Dermal-Epidermal Junction Constructs

Animal Models Development

• PLOD1-Knockout Mice
• FKBP14 Conditional Knockout Zebrafish
• Transgenic Rats with Tissue-Specific PLOD1 Suppression

As a preclinical research service provider, Protheragen develops therapies for rare skin diseases, including kyphoscoliotic Ehlers-Danlos Syndrome. Protheragen conducts GLA gene target validation, disease modeling, drug safety evaluation and DMPK services through fully integrated cell models, 3D organoids, and multi-organ animal models that recapitulate the pathology of kyphoscoliotic Ehlers-Danlos Syndrome.

Contact us to explore how our end-to-end solutions can advance your kyphoscoliotic Ehlers-Danlos Syndrome research.

References

• Ishikawa, Y., et al. "The Novel Missense Mutation Met48lys in Fkbp22 Changes Its Structure and Functions." Sci Rep 10.1 (2020): 497.
• Wiegand, A., et al. "Fkbp14 Kyphoscoliotic Ehlers-Danlos Syndrome Misdiagnosed as Larsen Syndrome: A Case Report." Cold Spring Harb Mol Case Stud 9.3 (2023).

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