Hypermobile Ehlers-Danlos Syndrome (hEDS) is a heritably connective tissue disorder which manifests as joint hypermobility, skin hyperextensibility, and tissue fragility. Protheragen facilitates the translational research of hEDS by providing comprehensive preclinical drug and therapy development services.
Introduction to Hypermobile Ehlers-Danlos Syndrome
Hypermobile Ehlers-Danlos Syndrome (hEDS) is the most prevalent subtype of EDS. It is characterized by joint hypermobility, chronic musculoskeletal pain, skin hyperextensibility, and the absence of a genetic marker, which complicates diagnosis. Recent studies suggest that dysregulated extracellular matrix (ECM) homeostasis, including perturbed collagen fibrillogenesis and deficiency of tenascin-X as major factors contributing to connective tissue fragility.
Fig.1 Location of the detected variants along the SERPINH1 gene. (Junkiert-Czarnecka
et al., 2023)
Pathogenesis of Hypermobile Ehlers-Danlos Syndrome
Dysregulated ECM homeostasis, including deficits in collagen fibrillogenesis and tenascin-X deficiencies, constitutes the pathogenesis of hEDS, although no specific genetic limiters have been pinpointed. Recent findings emphasize distinct sex differences, with increased prevalence noticed in females who are presumed to be more susceptible due to hormonal influences on pain perception (testosterone) and immune-inflammation modulation.
Therapeutics Development for Hypermobile Ehlers-Danlos Syndrome
Exploring Extracellular Matrix Modulation:
- Investigating HEDS is becoming prominent with changes being focused on extracellular matrix organization but with less attention being given to mechanics that lead to degeneration for a while.
- Both studies and researchers have recently been looking into how changes in the ECM, specifically in collagen and its associated processing enzymes, impact the pathophysiology of hypermobile Ehlers-Danlos Syndrome (hEDS).
- The focus of tissue engineering preclinical research is on developing new compounds or methods that could change the ECM's structure, synthesis, degradation, or assembly in order to preserve tissue integrity.
Targeting Molecular Pathways:
- The specifics of the molecular pathways affected in hEDS are also being studied in preclinical research.
- The work includes analysis of the cellular gene expression, protein domain interactions of the proteins, signaling pathways, as well as the processes that lead to softened connective tissues and malfunctioning cells.
- The intent is to discover promising pathways that could be used as drug development targets to provide therapeutic solutions to modify the adverse effects caused by hEDS.
Our Services
Protheragen offers full services to promote the treatment of hypermobile Ehlers-Danlos Syndrome. In collaboration with you, our team of scientist, dermatologists, and geneticists along with your project leads will assist in therapeutic development and disease model development tailored to the needs of the disorder using advanced technologies.
Therapeutic Development Platforms for Hypermobile Ehlers-Danlos Syndrome
Protheragen's platforms combine small molecule modulators to restore calcium signaling and autophagy, gene-targeted approaches for TENM3/COL5A1 expression to enhance collagen biosynthesis, and biologics (e.g., cytokine-neutralizing antibodies) to reduce inflammation.
Disease Model Development for Hypermobile Ehlers-Danlos Syndrome
Protheragen offers a full range of hypermobile Ehlers-Danlos Syndrome preclinical models with 2D cell models, 3D skin models as well as animal models development designed to replicate relevant disease pathologies and facilitate therapy development.
| 2D Cell Models & 3D Skin Models |
| Protheragen's preclinical research services for Hypermobile Ehlers-Danlos Syndrome include in vitro research activities at the interface with medicine for design and testing of safe and effective therapies. Employing 2D cell models and 3D skin models, we perform in vitro studies of the molecular mechanisms of the disease Hypermobile Ehlers-Danlos Syndrome. |
| Optional Models |
- Primary Human Dermal Fibroblasts
- iPSC-Differentiated Keratinocytes
|
- 3D Skin Organoids
- Collagen-Hyaluronan Hydrogel Co-Cultures
|
| Animal models |
| As part of our services, we offer in vivo preclinical studies. These studies make use of genetically engineering models to assess the safety and efficacy of test therapeutic agents. The animals used in these models are dependent on the relevance of the condition Hypermobile Ehlers-Danlos Syndrome. |
| Optional Models |
- TNXB Knockout (KO) Mice
- COL5A1 Haploinsufficient Mice
|
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| Optional Species |
Mice, Rats, Non-human primates, Others |
As a provider of preclinical research services with restricted access in a controlled environment, Protheragen seeks to promote the advancement of therapeutic strategies for rare skin diseases including Hypermobile Ehlers-Danlos Syndrome. We can provide end-to-end services from discovery through disease modeling and regulatory based drug safety evaluation and DMPK services. If you are interested in our services, please feel free to contact us.
References
- Junkiert-Czarnecka, A., et al. "The Role of Gene Encoding Collagen Secretion Protein (Serpinh1) in the Pathogenesis of a Hypermobile Type of Ehlers-Danlos Syndrome." Postepy Dermatol Alergol 40.1 (2023): 102-06.
- Rashed, E. R., et al. "Cardiovascular Manifestations of Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders." Vasc Med 27.3 (2022): 283-89.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
