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Pure Hair and Nail Ectodermal Dysplasia (PHNED)

Pure hair and nail ectodermal dysplasia (PHNED) is a type of congenital disorder that manifests in hair abnormalities and nail dysplasia. The inheritance pattern of PHNED occurs in both autosomal recessive and dominant forms. Protheragen provides comprehensive PHNED preclinical drug development and therapy development services to expedite translational therapies.

Overview of Pure Hair and Nail Ectodermal Dysplasia

Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder with autosomal recessive inheritance, with an incidence of 1 in 1,000,000, caused mainly by mutations in the HOXC13 gene that controls the expression of hair- and nail-specific keratins. The disorder manifests as isolated clinical features of hair and nail development. Unlike other ectodermal dysplasias, PHNED preserves the normal function of sweat glands and teeth. Dysfunction of HOXC13 leads to malformed epithelial differentiation which affects pathways vital for keratinization for hair follicles and the nail matrix.

The HOXC13 variant tolerance analysis with MetaDome.

Fig.1 HOXC13 variant tolerance analysis with MetaDome. (Clowes et al., 2024)

Pathogenesis of Pure Hair and Nail Ectodermal Dysplasia

PHNED stems from pathogenic variants of genes important for the development of ectodermal structures like hair follicles and nails, which includes HOXC13 and KRT85, disrupting their formation. These mutations result in insufficient keratinocyte differentiation and structural integrity which manifests as hair and nails that are ridged, thickened, or fragile. Compared with other ectodermal dysplasias, PHNED spares sweat glands and teeth, highlighting its impact on hair and nail ectodermal derivatives.

Therapeutics Development for Pure Hair and Nail Ectodermal Dysplasia

Gene Therapy
and Molecular
Interventions

Gene Therapy and Molecular Interventions: Recent research gives emphasis on correcting variations using CRISPR-Cas9 or viral vector gene delivery targeting HOXC13 or KRT85. Preclinical attempts showed that recovery of productive protein functioning enables restoration of functional protein expression. There is a need to refine efforts aimed at selective recognition of tissues. However, targeting blood vessels and surrounding tissues long term remains a challenge.

Keratinocyte
Differentiation
Modulators

Keratinocyte Differentiation Modulators: Research is underway with small molecules between Wnt/β-catenin or BMP pathways to promote keratinocyte differentiation and hair/nail matrix regeneration. A study found a BMP7 mimetic that increased nail plate thickness in KRT85-mutant organoid models. Also, topical rho-associated kinase (ROCK) inhibitors are being studied to limit hair follicle miniaturization based on insights from androgenetic alopecia treatment.

Our Services

Protheragen furthers pure hair and nail ectodermal dysplasia by providing advanced integrated preclinical services. This supports the innovation of therapeutic development, diagnostics development, and disease models to expedite translation. With proprietary platforms, we ensure a seamless transition from discovery to IND-enabling studies.

Therapeutic Development

Diagnostics Development

Biomarker Development
Single-Cell Spatial Transcriptomics
Proteomic Analysis of Keratin-Related Pathways
Diagnostic Kit Development
Multiplex NGS Panels for PHNED Genes
Point-of-Care qPCR Kits

Disease Model Development

Patient-Derived Primary Keratinocytes
Immortalized Keratinocytes
HOXC13 c.571_572insG Knock-In Mice
KRT85 p.Leu132Pro Transgenic Zebrafish
KRT85 Conditional Knockout Mice

To expedite preclinical translation for pure hair and nail ectodermal dysplasia, Protheragen employs sophisticated in vitro alongside in vivo technologies. Integrated drug safety evaluation and DMPK enables rapid validation of therapeutic strategies, mechanistic verification, and subsequent efficacy testing.

Partner with us to pure hair and nail ectodermal dysplasia research into viable therapeutic innovations. For inquiries regarding our comprehensive services, please contact us.

References

Clowes, V., et al. "Homozygous Hoxc13 Variant Causes Pure Hair and Nail Ectodermal Dysplasia Via Reduction in Protein Stability." Hum Mutat 2024 (2024): 6420246.
Humbatova, A., et al. "An Insertion Mutation in Hoxc13 Underlies Pure Hair and Nail Ectodermal Dysplasia with Lacrimal Duct Obstruction." Br J Dermatol 178.4 (2018): e265-e67.

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