Congenital Reticular Ichthyosiform Erythroderma (CRIE), which is referred to as ichthyosis with confetti, is a genetically rare skin condition that is characterized by erythroderma, scaling, and spontaneous revertant mosaicism. At Protheragen, we provide comprehensive preclinical drug and therapy development initiatives, geared to facilitate therapeutic advances for this debilitating condition.
Overview of Congenital Reticular Ichthyosiform Erythroderma
Congenital Reticular Ichthyosiform Erythroderma (CRIE) is an autosomal dominant disorder caused by mutations in keratin genes (KRT10/KRT1), which leads to defective epidermal barrier function. Clinically, affected individuals display generalized erythema, hyperkeratosis, and distinctive "confetti" macules of normal skin in otherwise diseased epidermis due to somatic reversion. The reported incidence of the disease is approximately 1 in 1,000,000, and previous studies have reported variability in the severity of disease determining the KRT10 or KRT1 mutation of keratin expression which affect keratin filament assembly, the degree of hyperkeratinization, epidermal inflammation, and the resulting breakdown of epidermal barrier function.
Fig.1 Histology and immunofluorescence findings in ichthyosis with confetti caused by KRT10 mutation. (Guerra
et al., 2015)
Diagnostic Development for Congenital Reticular Ichthyosiform Erythroderma
Genetic Testing
Next-generation sequencing (NGS) panels to identify KRT10/KRT1 mutations will allow improved genomic resolution for detection of pathogenic variants, inclusive of detection of mosaic mutations of KRT10/KRT1 due to somatic reversion. Technical advances in the long-read sequencing platform have recently extended the ability to detect highly complex structural variants or deep intronic mutations that would go undetected with traditional genome sequencing methods.
Biomarker Identification
The detailed proteomic profiling of skin biopsy via mass spectrometry and antibody arrays can identify dysregulated pathways. Unique to CRIE patients, single-cell RNA sequencing demonstrated that patient-derived keratinocytes exhibited subtype specific signatures (i.e., overexpression of pro-inflammatory cytokines for targeted gene therapy), thereby guiding the prioritization of therapeutic goals in dysregulation.
Therapeutics Development for Congenital Reticular Ichthyosiform Erythroderma
Current therapeutics strategies in the treatment of congenital epidermolysis bullosa ranges from efforts to restore epidermal barrier function, to reduction of inflammation, to gene correction of genetic defects.
Table.1 Therapeutic Development Pipeline for Congenital Reticular Ichthyosiform Erythroderma.
| Therapeutic Approach |
Therapeutic Target/Goal |
Development Stage |
Key Studies/Evidence |
Current Status |
| Topical Enzyme Replacement |
Transglutaminase 1 (TGM1) protein |
Preclinical |
Recombinant TGM1 restored epidermal barrier in TGM1−/− mice |
Efficacy in animal models; formulation optimization ongoing. |
| Gene Therapy |
ALOX12B gene |
Preclinical |
AAV mediated ALOX12B delivery improved skin pathology in mice |
Proof-of-concept in animals; safety studies pending. |
| Gene Therapy |
TGM1 mutation correction |
Preclinical |
Ex vivo repair of TGM1mutations in patient keratinocytes |
Editing efficiency ~50%; in vivo delivery challenges unresolved. |
| Small Molecules (Retinoids) |
Retinoic acid receptors |
Phase II Clinical Trial |
Oral acitretin reduced scaling in CRIE patients. |
Limited efficacy on erythema; long-term safety monitoring required. |
| Biologicals (IL-17 Inhibitors) |
Inflammatory cytokines |
Phase I Clinical Trial |
Secukinumab (anti-IL-17A) tested for inflammation control |
Preliminary reduction in skin inflammation; efficacy endpoints under evaluation. |
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 provides a full spectrum of services for therapy advancement in congenital reticular Ichthyosiform erythroderma. Our team of scientist, dermatologists and experience geneticists employ state-of-the-art technologies and interdisciplinary efforts focused toward facilitating therapeutic development, diagnostics development as well as disease model development services advance your research project.
- Patient-Derived Primary Keratinocytes
- KRT10/KRT1-Mutant Keratinocytes
- KRT10 Knock-in Mice
- Conditional KRT1 Epidermal Mutant Mice
At Protheragen, we provide comprehensive preclinical therapeutics services toward disease from discovery to development. Our state-of-the-art facilities and experienced team conduct rigorous in vitro and in vivo studies to evaluate the safety and efficacy of potential therapeutics, ensuring that your drug candidates meet the highest standards.
Partner with us to accelerate your congenital reticular ichthyosiform erythroderma research and transform therapeutic innovations into effective solutions. If you are interested in our services, please contact us.
References
- Dvorakova, V., et al. "Congenital Reticular Ichthyosiform Erythroderma." Clin Exp Dermatol 41.5 (2016): 576-7.
- Guerra, L., et al. "Ichthyosis with Confetti: Clinics, Molecular Genetics and Management." Orphanet J Rare Dis 10 (2015): 115.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
