Epidermolytic ichthyosis (EI) is a genetic skin disorder that is uncommon and presents with widespread blistering, erythroderma, and hyperkeratosis caused by mutations in either KRT1 or KRT10. Protheragen is able to provide end-to-end preclinical drug and therapy development services for EI leveraging state-of-the-art technologies to help hasten new advancements in diagnostics and therapeutics.
Overview of Epidermolytic Ichthyosis
Epidermolytic Ichthyosis (EI) is an autosomal dominant condition previously referred to as epidermolytic hyperkeratosis, due to pathogenic variants in keratin genes (KRT1 or KRT10). These genetic variants lead to a disruption of the assembly of keratin filaments resulting in irritability, mottled erythema, and excessive scaling. Recent evidence also suggests the importance of dysregulated keratinocyte differentiation and immune dysregulation in the disease. EI occurs in neonatal infancy with blistering that thickens and fissures the skin.
Fig.1 Epidermolytic Ichthyosis and the correction of its dominant-negative phenotype using TALEN-mediated gene editing. (March
et al., 2019)
Diagnostic Development for Epidermolytic Ichthyosis
Enhanced Genetic Profiling: Third-generation sequencing technologies, like long-read sequencing can now precisely detect complex structural variants in KRT1/KRT10 genes, such as deep intronic or mosaic mutations which were previously impossible to detect by short-read NGS.
Multi-Omics Biomarker Integration: Proteomic and transcriptomic analyses of epidermal samples have discovered new biomarker panels in epidermal samples of dysregulated keratin-associated proteins and inflammatory cytokines (e.g., IL-36γ) that correlate with disease severity.
Therapeutics Development for Epidermolytic Ichthyosis
Recent preclinical therapeutic strategies for rare genetic skin conditions have focused on molecular intervention approaches including gene editing, antisense oligonucleotides (AONs), protein replacement and small molecule therapy.
Table.1 Therapeutic Development for Epidermolytic Ichthyosis.
| Therapy/Drug |
Target |
Stage |
Mechanism |
| DIRECT-Duo |
KRT10 pre-mRNA |
Preclinical |
AON-mediated exon skipping |
| TBI-201 |
Mutant keratin aggregates |
Phase I completed |
Topical antioxidant inhibiting aggregation |
| KB105 |
KRT10 gene |
Phase I/II |
HSV-1 vector delivering functional KRT10 |
| KER-047 |
ALK2 receptor |
Phase I |
Oral ALK2 inhibitor modulating iron metabolism |
| Alitretinoin |
Retinoic acid receptors |
Phase II/III |
Oral retinoid reducing hyperkeratosis |
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 a wide range of full services to develop therapeutics for epidermolytic ichthyosis. Our team of scientists, dermatologists, and geneticists utilize cutting-edge technologies to advance therapeutic development, diagnostics development as well as disease model development services for your projects.
- Patient-Derived Primary Keratinocytes
- HaCaT Cell Lines
- Reconstructed Human Epidermal Equivalents
- KRT1 Conditional Knock-In Mice
- KRT10 Mutant Mice
Protheragen provides integrated preclinical services to support the advancement of epidermolytic ichthyosis therapeutics from discovery to development. he advanced technologies and expertise of our experienced team provides rigor in testing of your therapeutics in vitro and in vivo to demonstrate sufficient safety and efficacy for your candidate drug.
Partner with us and expedite your epidermolytic ichthyosis research and therapeutic innovations into practice. If you are interested in our services, please contact us.
References
- Frommherz, L., et al. "Epidermolytic Ichthyosis: Clinical Spectrum and Burden of Disease in a Large German Cohort." J Eur Acad Dermatol Venereol (2024).
- March, O. P., et al. "Gene Editing-Mediated Disruption of Epidermolytic Ichthyosis-Associated Krt10 Alleles Restores Filament Stability in Keratinocytes." J Invest Dermatol 139.8 (2019): 1699-710 e6.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
