RARE DISEASE
Ichthyosis
Ichthyosis
Ichthyosis
Drug discovery
1
drug
With orphan designation
Overview
Ichthyosis encompasses genetic and acquired disorders of keratinization characterized by dry, thickened, scaling skin due to impaired barrier function and abnormal desquamation. While most forms are inherited (e.g., ichthyosis vulgaris, X-linked, lamellar), acquired cases may arise from systemic diseases or medications. Symptoms range from mild xerosis to life-threatening erythroderma, often with complications like infections, ectropion, and heat intolerance. Management focuses on symptomatic relief through emollients, keratolytics, and retinoids, with emerging therapies targeting underlying genetic mechanisms [1][8][12].
Burden
Categories: rare skin diseases
Research Papers
854 drug discovery papers related to Ichthyosis, with 6 first-in-class and 9 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
854 drug discovery papers related to Ichthyosis, with 6 first-in-class and 9 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-06 | The role of dupilumab in skin microbiome shifts in the Netherton genodermatosis: a case report and review of literature.
Skin dysbiosis plays a crucial role in inflammatory skin diseases, particularly in genodermatoses such as Netherton syndrome (NS). This case report aimed to investigate changes in the skin microbiome of a patient with Netherton syndrome before and during dupilumab therapy, with the goal of expanding the limited evidence currently available on this topic. We report the case of a 35-year-old woman diagnosed with NS at birth, who, prior to dupilumab therapy, presented with atopic dermatitis (AD), ichthyosis linearis circumflexa, and severe pruritus. Dupilumab therapy was initiated, and skin swabs were collected from lesional sites at three different time points: at baseline, after 1 month, and after 1 year of continuous dupilumab therapy. At baseline, a microbiome analysis revealed low microbial diversity with a predominance of Pantoea and Pseudomonas species. After 1 year, a significant increase in microbial diversity, with a predominance of Staphylococcus species and an increase in Malassezia species, was observed. Clinically, the patient experienced remission in parallel with these microbiome shifts. Post-treatment, the skin microbiome showed increased microbial diversity and re-establishment of beneficial commensals, more closely resembling healthy skin. The findings of this case report underscore the role of dupilumab in restoring a healthy skin microbiome along with symptomatological and clinical improvement in the genodermatosis Netherton syndrome.
2026-07-03 | Two clinical observations of keratitis-ichthyosis-deafness syndrome (KID syndrome)
Keratitis-ichthyosis-deafness (KID) syndrome is a rare genetic disorder characterized by erythrokeratoderma, vascular keratitis and sensorineural hearing loss. The disease develops as a result of a mutation in the GJB2 gene encoding the connexin 26 protein, which is expressed in the epidermis and is involved in the formation of gap junctions between epithelial cells that carry out transport of ions and small molecules. Changes in the skin are usually noticed from birth, they may manifest as erythrokeratoderma, psoriasis-like lesions, hyperkeratosis foci, palmoplantar keratoderma. Alopecia totalis progresses with age. Congenital bilateral prelingual sensorineural hearing loss is diagnosed in 90% of patients, and neovascular keratitis — in 95%. Half of the patients experience persistent skin infection, and the development of benign and malignant tricholemmal tumors as well as squamous cell carcinoma is possible. In recent years, a search for drugs capable of restoring the patency of gap junction channels, which significantly improves the skin condition in research animals, has been performed. Effective therapeutic agents will be discovered in the future. Currently, patients are primarily treated symptomatically. We present a case report of two patients suffering from KID syndrome. In both cases, the disease began from birth and was manifested by ichthyosiform erythroderma, palmoplantar keratoderma, alopecia totalis, onychodystrophy, sensorineural deafness, chronic keratitis and photophobia. Despite the full set of diagnostic symptoms, the first patient was diagnosed with KID syndrome at the age of 29, and the second patient — at the age of 10. In the second case, genetic analysis confirmed the GJB2 gene mutation (p.Asp50Asn). The course of the disease was accompanied by a persistent bacterial infection, manifesting as the formation of abscesses, predominantly in the head area, and cracks on the skin of the extremities. An improvement in the skin condition was observed in presence of symptomatic therapy with antibacterial agents, emollients and retinoids.
2026-06-23 | P34 Targeted base editing restores genetic integrity in epidermolytic ichthyosis patient cells
Abstract Introduction and aims Epidermolytic ichthyosis (EI) is an epidermal differentiation disorder caused by pathogenic variants in KRT1 and KRT10, reducing cytoskeletal stability in suprabasal keratinocytes. Many of these pathogenic variants are single-nucleotide substitutions suitable for correction by base editing, a precise CRISPR-based genome editing approach that enables targeted conversion of one nucleotide to another. We propose that genetic correction of EI-associated variants using base editors could offer a curative therapeutic strategy. Methods Our current work utilizes two-dimensional, patient-derived keratinocyte and fibroblast cultures heterozygous for the KRT10c.467G>A variant. These keratinocytes display characteristic EI phenotypes, including cytoskeletal abnormalities, reduced proliferative potential, flattened morphology from passage three, and senescence by passage five. This has prompted us to develop and validate immortalized EI keratinocyte lines for future studies. In contrast, EI fibroblasts exhibit rapid growth and long-term culture stability, making them valuable for initial optimization of editing conditions. Our initial editing has utilized lipid nanoparticle (LNP)-delivered ABE8e adenine base editor, and assessed outcomes by Sanger and amplicon sequencing. Results To date, we have performed base editing on primary EI keratinocytes using the ABE8e. We achieved 100% on-target editing efficiency, accompanied by a 23% undesired bystander edit. We are now optimizing ABE8e dosage to minimize bystander effects and are synthesizing a next-generation ABE9 variant with a narrower editing window to avoid bystander edits at this locus. Next, we will assess functional correction of the pathogenic variant through protein analysis and visualization of cytoskeletal aggregates under stress conditions. For further validation, we aim to establish a three-dimensional EI skin model and evaluate topical delivery of our editing system using LNP formulations currently being developed in our laboratory. Conclusions In conclusion, our findings demonstrate the feasibility of base editing as an efficient gene-editing strategy for EI and outline a translational pipeline that could ultimately provide a new therapeutic avenue for patients.
2026-07-06 | The role of dupilumab in skin microbiome shifts in the Netherton genodermatosis: a case report and review of literature.
Skin dysbiosis plays a crucial role in inflammatory skin diseases, particularly in genodermatoses such as Netherton syndrome (NS). This case report aimed to investigate changes in the skin microbiome of a patient with Netherton syndrome before and during dupilumab therapy, with the goal of expanding the limited evidence currently available on this topic. We report the case of a 35-year-old woman diagnosed with NS at birth, who, prior to dupilumab therapy, presented with atopic dermatitis (AD), ichthyosis linearis circumflexa, and severe pruritus. Dupilumab therapy was initiated, and skin swabs were collected from lesional sites at three different time points: at baseline, after 1 month, and after 1 year of continuous dupilumab therapy. At baseline, a microbiome analysis revealed low microbial diversity with a predominance of Pantoea and Pseudomonas species. After 1 year, a significant increase in microbial diversity, with a predominance of Staphylococcus species and an increase in Malassezia species, was observed. Clinically, the patient experienced remission in parallel with these microbiome shifts. Post-treatment, the skin microbiome showed increased microbial diversity and re-establishment of beneficial commensals, more closely resembling healthy skin. The findings of this case report underscore the role of dupilumab in restoring a healthy skin microbiome along with symptomatological and clinical improvement in the genodermatosis Netherton syndrome.
2026-07-03 | Two clinical observations of keratitis-ichthyosis-deafness syndrome (KID syndrome)
Keratitis-ichthyosis-deafness (KID) syndrome is a rare genetic disorder characterized by erythrokeratoderma, vascular keratitis and sensorineural hearing loss. The disease develops as a result of a mutation in the GJB2 gene encoding the connexin 26 protein, which is expressed in the epidermis and is involved in the formation of gap junctions between epithelial cells that carry out transport of ions and small molecules. Changes in the skin are usually noticed from birth, they may manifest as erythrokeratoderma, psoriasis-like lesions, hyperkeratosis foci, palmoplantar keratoderma. Alopecia totalis progresses with age. Congenital bilateral prelingual sensorineural hearing loss is diagnosed in 90% of patients, and neovascular keratitis — in 95%. Half of the patients experience persistent skin infection, and the development of benign and malignant tricholemmal tumors as well as squamous cell carcinoma is possible. In recent years, a search for drugs capable of restoring the patency of gap junction channels, which significantly improves the skin condition in research animals, has been performed. Effective therapeutic agents will be discovered in the future. Currently, patients are primarily treated symptomatically. We present a case report of two patients suffering from KID syndrome. In both cases, the disease began from birth and was manifested by ichthyosiform erythroderma, palmoplantar keratoderma, alopecia totalis, onychodystrophy, sensorineural deafness, chronic keratitis and photophobia. Despite the full set of diagnostic symptoms, the first patient was diagnosed with KID syndrome at the age of 29, and the second patient — at the age of 10. In the second case, genetic analysis confirmed the GJB2 gene mutation (p.Asp50Asn). The course of the disease was accompanied by a persistent bacterial infection, manifesting as the formation of abscesses, predominantly in the head area, and cracks on the skin of the extremities. An improvement in the skin condition was observed in presence of symptomatic therapy with antibacterial agents, emollients and retinoids.
2026-06-23 | P34 Targeted base editing restores genetic integrity in epidermolytic ichthyosis patient cells
Abstract Introduction and aims Epidermolytic ichthyosis (EI) is an epidermal differentiation disorder caused by pathogenic variants in KRT1 and KRT10, reducing cytoskeletal stability in suprabasal keratinocytes. Many of these pathogenic variants are single-nucleotide substitutions suitable for correction by base editing, a precise CRISPR-based genome editing approach that enables targeted conversion of one nucleotide to another. We propose that genetic correction of EI-associated variants using base editors could offer a curative therapeutic strategy. Methods Our current work utilizes two-dimensional, patient-derived keratinocyte and fibroblast cultures heterozygous for the KRT10c.467G>A variant. These keratinocytes display characteristic EI phenotypes, including cytoskeletal abnormalities, reduced proliferative potential, flattened morphology from passage three, and senescence by passage five. This has prompted us to develop and validate immortalized EI keratinocyte lines for future studies. In contrast, EI fibroblasts exhibit rapid growth and long-term culture stability, making them valuable for initial optimization of editing conditions. Our initial editing has utilized lipid nanoparticle (LNP)-delivered ABE8e adenine base editor, and assessed outcomes by Sanger and amplicon sequencing. Results To date, we have performed base editing on primary EI keratinocytes using the ABE8e. We achieved 100% on-target editing efficiency, accompanied by a 23% undesired bystander edit. We are now optimizing ABE8e dosage to minimize bystander effects and are synthesizing a next-generation ABE9 variant with a narrower editing window to avoid bystander edits at this locus. Next, we will assess functional correction of the pathogenic variant through protein analysis and visualization of cytoskeletal aggregates under stress conditions. For further validation, we aim to establish a three-dimensional EI skin model and evaluate topical delivery of our editing system using LNP formulations currently being developed in our laboratory. Conclusions In conclusion, our findings demonstrate the feasibility of base editing as an efficient gene-editing strategy for EI and outline a translational pipeline that could ultimately provide a new therapeutic avenue for patients.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Ichthyosis.
1 orphan drug designation for Ichthyosis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
urea | small molecules | FDA | 2011-11-07 | — | Orenova Group, LLC |
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