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Project Description

Please note that we are not a pharmacy or clinic, so we are unable to see patients and do not offer diagnostic and treatment services for individuals.

Hypohidrotic Ectodermal Dysplasia (HED)

Hypohidrotic Ectodermal Dysplasia (HED) is a genetic condition that is characterized by an alteration in the ectodermal features and results from mutations in EDA, EDAR, or EDARADD genes that cause disruption of EDA signaling cascade. Protheragen provides extensive services for preclinical development of HED which includes target validation, biomarker development, advanced modeling of the disease, and therapeutic interventions.

Introduction to Hypohidrotic Ectodermal Dysplasia

HED is described by triad symptoms: hypohidrosis, hypotrichosis and hypodontia. The EDA mutations lead to impaired NF-κB signaling which is important for ectodermal differentiation. More recent works describe other complications like respiratory system infections related to seal faults and intolerance to high temperatures. There is phenotypic variation, where those with X-linked heterozygote forms (EDA mutations) being the most severe, and autosomal forms (EDAR and EDARADD) being much milder.

The domain organization of EDA·A1 and EDAR.

Fig.1 Domain organization of EDA·A1 and EDAR. (Yu et al., 2023)

Biomarkers Development for Hypohidrotic Ectodermal Dysplasia

EDA Protein Levels: Quantification of plasma EDA-A1 isoform using ELISA in X-linked HED patients correlates with severity of the disease. Predicts low EDA-A1 will result in the loss of function of sweat glands.

NF-κB Activity: The deficiency of gene expression, Shh and Wnt10a which are the targets of NF-κB, will be reduced in keratinocytes stem cells obtained from patients and serve as a functional biomarker.

Salivary Proteomics: The increased levels of IL-17 and TGF-β in saliva are indicative of chronic inflammation of the mucosa, helping to monitor respiratory inflammation sequelae.

Therapeutics Development for Hypohidrotic Ectodermal Dysplasia

Therapeutic Strategy	Therapeutic Target	Key Findings/Mechanism	Development Stage
Recombinant EDA Protein	EDA-A1 replacement	Subcutaneous EDI200 (rEDA-A1) restores sweating and dental development in pediatric trials.	Phase III
Gene Therapy	EDA gene delivery	AAV9-EDA in neonatal mice rescues sweat glands; early human trials show hair follicle regeneration.	Phase I/II
Small Molecule Agonists	EDAR receptor activation	SMACoA-EDAR agonists activate NF-κB in vitro, reversing keratinocyte differentiation defects.	Preclinical
Stem Cell Therapy	iPSC-derived ectodermal progenitors	iPSCs differentiated into sweat gland precursors show engraftment potential in rodent models.	Preclinical
Anti-inflammatory Agents	IL-17/TGF-β inhibition	Tocilizumab (anti-IL-6R) reduces salivary gland inflammation in HED patients.	Phase I

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 has advanced thought of hypohidrotic ectodermal dysplasia therapeutic development by providing integrated preclinical solutions, making us unique in the industry. Our specialists employ sophisticated tools for fast tracked drug and diagnostic development, working in synergy with robust therapeutic and advanced disease models.

Therapeutics Development Platforms for Hypohidrotic Ectodermal Dysplasia

Disease Model Development for Hypohidrotic Ectodermal Dysplasia

Protheragen custom designs HED pathology-relevant 2D cell models, 3D skin models as well as animal models that include impairment of sweat gland morphogenesis, ectodermal progenitor differentiation, and NF-κB signaling dysregulation.

2D Cell Models & 3D Skin Models

Patient-Derived Keratinocytes with EDA Mutations
iPSC-Derived Ectodermal Progenitor Cells
3D Ectodermal Organoids

Animal Models Development

Conditional EDA Knockout Mice
Humanized EDAR p.R92H Transgenic Mice
EDARADD Knockout Rats
Canine X-linked HED Models

As a preclinical research service provider, Protheragen develops therapies for rare skin diseases, such as hypohidrotic ectodermal dysplasia. Protheragen performs GLA gene target validation, disease modeling, drug safety evaluation and DMPK services using fully integrated cell models, 3D organoids, and multi-organ animal models which have hypohidrotic ectodermal dysplasia pathology.

Contact us to explore how our end-to-end solutions can advance your hypohidrotic ectodermal dysplasia research.

References

Graversen, L., et al. "Hypohidrotic Ectodermal Dysplasia Caused by an Intragenic Duplication in Edar." Eur J Med Genet 72 (2024): 104982.
Yu, K., et al. "Structural Insights into Pathogenic Mechanism of Hypohidrotic Ectodermal Dysplasia Caused by Ectodysplasin a Variants." Nat Commun 14.1 (2023): 767.

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