Superficial Epidermolytic Ichthyosis (SEI) is a rare autosomal dominant keratinization disorder characterized by superficial skin blistering, hyperkeratosis, and erosions, caused by mutations in the KRT2 gene. Leveraging Protheragen's expertise in nephrology, our company aims to design therapies that target the dermatologic and systemic consequences of SEI.
Superficial Epidermolytic Ichthyosis (SEI) is a very rare condition that is characterized by an autosomal dominant form of blistering, hyperkeratosis, and erosive skin with a genetic mutation (KRT2) located in the superordinate level of the hierarchy. SEI is primarily a skin condition, but some studies show a systemic involvement with end-stage renal failure and renal tubular acidosis due to uncontrolled inflammation and metabolic burden in more severe cases.
SEI is caused by single-point mutations in one copy of KRT2 that produce an intermediate filament of keratin 2 in the basal part of the upper layers of the epidermis. It causes the granular and corneocyte layers to undergo cytolysis, which leads to the exacerbation of inflammation and imperfect shedding. Possibilities of extreme cases of chronic inflammation, oxidative damage, and metabolic derangement show up renal dysfunction in more severe phenotypes. Dermal-epidermal hyperkeratosis with vacuolar degeneration is also an evident histological feature due to poor skin-renal interaction
Fig.1 Histology shows orthokeratosis and disruption of cytoplasm in keratinocytes of stratum spinosum leading to vesicles formation and intraepidermal separation. (Osipowicz et al., 2021)| Therapeutic Strategy | Drug Name | Target/Mechanism | Key Findings/Efficacy | Development Stage |
| Systemic Retinoids | Alitretinoin | Activates RXR/RAR nuclear receptors | 30 mg/day for 6 months reduces lesions by 60% and pruritus by 50% in 9 SEI patients. | Phase II |
| Gene Therapy | CRISPR-Cas9/KRT10 mRNA | Corrects KRT10 mutations | >90% mutation correction in keratinocytes; restores keratin filament networks. | Preclinical |
| Protein Repair Therapy | Recombinant Keratin Nanoparticles | Delivers functional KRT10 | Liposome-encapsulated KRT10 reduces epidermal acantholysis by 80% in animal models. | Preclinical |
| Novel Metabolic Modulators | N-Acetylcysteine (NAC) | Boosts glutathione synthesis | 10% topical gel reduces epidermal desquamation via cysteine protease inhibition. | 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.
Protheragen offers comprehensive services to advance therapies for rare skin disorders such as superficial epidermolytic ichthyosis. Our team of scientists, dermatologists, and geneticists collaborates to develop precision therapeutic and disease model, supporting research from early discovery to IND-enabling studies.
Protheragen designs SEI-specific models including 2D cell models, 3D skin models and animal models that replicate the molecular pathology of keratin network disruption and epidermal acantholysis.
In Vivo Pharmacokinetics Services
As a leader in rare skin disease research, Protheragen bridges the gap between discovery and clinical translation. Our integrated platform ensures seamless progression from target validation and disease modeling to drug safety evaluation to DMPK services, all tailored to SEI's unique pathology.
Contact us to accelerate your SEI therapeutic programs with our end-to-end preclinical expertise.
References
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