Vascular Ehlers-Danlos Syndrome (vEDS) is a dangerously progressive genetic disease of the type autosomal dominant inheritance caused by mutations in the COL3A1 gene located on chromosome 2q32.2, which encodes for type III collagen. As an industry-leader in dermatological therapy development, Protheragen has been addressing the multifaceted problems of vEDS by offering a prototypical fordering-from-discovery-to-drug-safety evaluation solution model
Introduction to Vascular Ehlers-Danlos Syndrome
Vascular Ehlers-Danlos syndrome (vEDS), also referred to as Ehlers-Danlos Syndrome Type IV, is an uncommon form of severe autosomal dominant connective tissue disorder. Pathogenic variants regarding this manually stem from COL3A1 gene located at chromosome 2q31, responsible for encoding the α1(III) chain of type III procollagen. This vital protein contributes significantly to the formation of blood vessels, hollow organs, and skin tissues. While estimating its prevalence remains difficult due to underreporting or misdiagnosis, it's roughly believed that about 1 in 50 000 to 200 000 people suffer from it worldwide.
Pathogenesis of Vascular Ehlers-Danlos Syndrome
This condition results from dominant-negative mutations within the COL3A1 gene that disrupt triple-helix assembly and secretion of collagen leading to vEDS. The patient suffers from retinal detachment along with process aberrations including er stress arising due to misfolded collagens triggering endoplasmic reticulum stress resulting within Unfolded protein response system pathways compromising weak attachment between smooth vascular muscle and collagen bases membrane integrity dysregulation.
Fig.1 Radiological and pathological features of the present case. (Hwang, Song and Jang, 2022)
Therapeutics Development for Vascular Ehlers-Danlos Syndrome
| Therapeutic Strategy |
Mechanism/Target |
Key Findings/Results |
Development Stage |
| Celiprolol |
β1-adrenergic receptors |
Selective β1-antagonist/β2-agonist; reduces vascular wall mechanical stress to prevent arterial rupture |
Phase IV |
| Metoprolol |
β-adrenergic receptors |
Nonselective β-blocker; lowers heart rate and blood pressure |
Approved |
| Losartan |
Angiotensin II receptor |
ARB inhibitor; suppresses TGF-β signaling and vascular remodeling |
Preclinical |
| DB102 (Enzastaurin) |
PKCβ/PI3K/AKT pathway |
Oral kinase inhibitor; restores vascular matrix integrity |
Phase I |
| AAV-COL3A1 Therapy |
COL3A1 gene |
Viral vector delivery of functional type III collagen cDNA |
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 offers comprehensive therapeutic development and disease model development services to support the advancement of vEDS therapies. Our team of scientists, geneticists, dermatologists, and other specialists leverage advanced disorder-specific technologies to facilitate effective therapy development.
Therapeutic Development Platforms for vEDS
Protheragen's platforms include small molecule therapeutics for stabilizing vascular matrix integrity, gene therapy for precision COL3A1 modification aimed at restoring collagen biosynthesis, and biologics to mitigate vascular fragility and enhance connective tissue resilience in vEDS.
Disease Model Development for vEDS
Protheragen offers vEDS preclinical models including 2D cell models, 3D skin models, and animal models that recapitulate the relevant pathophysiological changes of the disease for therapeutic intervention screening.
- COL3A1G209S Mutant Vascular SMC Model
- Patient-Derived Fibroblast Model
- 3D Vascular Organoid with Spontaneous Rupture Phenotype
- Col3a1 Knockout Mice
- Endothelial-Specific COL3A1 Conditional Knockout Mice
- Hemodynamic Stress-Induced Aneurysm Model
Drug Safety Evaluation and DMPK Services for vEDS
Protheragen offers comprehensive drug safety evaluation and DMPK services, designed to accelerate your vEDS therapeutic development with integrated non-GLP platforms, designed to de-risk vascular-targeted candidates and prevent collagen disruption.
- Metabolic Stability Assa
- CYP Inhibition Screening
- Plasma Protein Binding
- Caco-2 Permeability
- Hepatocyte Clearance
- Oral Bioavailability
- Tissue Distribution
- Excretion Balance
- Metabolite Profiling
- Skin Penetration Study
Protheragen provides comprehensive preclinical research services specifically tailored to the pathology of Vascular Ehlers-Danlos Syndrome. We offer a full scope of services, from early discovery and disease modeling to drug safety evaluation and DMPK services. If you are interested in our services or would like to discuss potential collaborations, please feel free to contact us.
References
- Hwang, H. S., J. W. Song, and S. J. Jang. "Vascular Ehlers-Danlos Syndrome with Distinct Histopathologic Features." J Pathol Transl Med 56.3 (2022): 167-69.
- Lyness, J. R., and P. J. Morrison. "The Dysmorphic Phenotype in Vascular Ehlers Danlos Syndrome." Clin Dysmorphol 32.1 (2023): 1-6.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
