Research Hub
The latest on gene therapy trials, drug development, key researchers, and how to get involved in studies.
Research moves fast: This page was last reviewed March 2026. For the most current trial status, check ClinicalTrials.gov directly and ask your dermatologist at each visit.
Drug Pipeline — 2025 to 2028
KB105
Krystal Biotech
Target: Lamellar Ichthyosis (TGM1 mutations)
Phase 2 Completed
Recombinant herpes simplex virus vector delivering functional TGM1 gene directly to keratinocytes. Phase 2 results (2023) demonstrated statistically significant reduction in scale severity at treated sites vs placebo. Pivotal Phase 3 trial under discussion. Most advanced gene therapy for ichthyosis in the pipeline.
Beremagene geperpavec (B-VEC)
Krystal Biotech
Target: Dystrophic Epidermolysis Bullosa (adjacent condition)
FDA Approved (EB) 2023
Though approved for EB rather than ichthyosis, this is the first approved topical gene therapy for any skin condition. The HSV vector technology is directly related to KB105, validating the approach for ichthyosis gene therapy development.
Dupilumab (Dupixent)
Sanofi / Regeneron
Target: Netherton Syndrome (IL-4/IL-13 blockade)
Phase 2 / Case Series Evidence
Growing published case series showing marked improvement in Netherton syndrome — reduction in redness, itch, and inflammatory scale. Currently off-label in UK for ichthyosis. NHS approval pathway under review. Discuss with your dermatologist if other treatments have failed.
Anti-IL-17 biologics (Secukinumab, Ixekizumab)
Multiple manufacturers
Target: Netherton Syndrome, severe Lamellar
Case Reports / Early Phase
IL-17 pathway appears elevated in some ichthyosis types. Individual case reports of improvement in Netherton. Systematic investigation underway. Currently off-label — specialist only.
Liarozole
Multiple — generic
Target: X-Linked Ichthyosis, Lamellar
Phase 2 Completed
Retinoic acid metabolism inhibitor — increases endogenous retinoic acid without direct retinoid administration. Phase 2 trials demonstrated efficacy in X-linked ichthyosis with potentially improved side-effect profile vs acitretin. Available via named-patient mechanism in some countries.
Topical cholesterol + lovastatin 2%/2%
Compounded — no manufacturer
Target: CHILD Syndrome only
Case Study Evidence
Breakthrough for CHILD syndrome. 2015 Journal of Investigative Dermatology case studies showed near-complete resolution of CHILD nevus in some patients. Corrects the local NSDHL-driven cholesterol synthesis deficiency. Must be compounded — not commercially available.
Key Milestones in Ichthyosis Research
1985
STS gene identified — X-linked ichthyosis
Steroid sulphatase gene located on X chromosome. First molecular basis of ichthyosis defined.
2006
FLG mutations identified in Ichthyosis Vulgaris and Eczema
Professor Irwin McLean's group (Dundee). One of the most significant genodermatology discoveries — also linked FLG to atopic eczema worldwide.
2015
Cholesterol/lovastatin breakthrough for CHILD syndrome
Journal of Investigative Dermatology: dramatic improvement with topical cholesterol + lovastatin 2%/2% in CHILD syndrome nevus — disease-modifying, not just symptomatic.
2020 to 2022
Dupilumab case series published in Netherton
Multiple published reports showing marked improvement — changing management for severe Netherton syndrome that was previously very difficult to treat.
2023
KB105 Phase 2 results — TGM1 gene therapy
Krystal Biotech published statistically significant Phase 2 results for topical gene therapy in lamellar ichthyosis. First gene therapy to reach this stage for any ichthyosis type.
2023
B-VEC FDA approval — first skin gene therapy
FDA approved beremagene geperpavec for dystrophic EB — first ever approved skin gene therapy. Validates the HSV vector platform used in KB105.
2025 to 2027 (expected)
KB105 Phase 3 trial and potential regulatory submission
If Phase 3 proceeds and succeeds, lamellar ichthyosis could have its first approved gene therapy before 2030 — transforming management for TGM1-mutation patients.
Ichthyosis Gene Reference
| Gene | Protein / Function | Type | Inheritance | Key Notes |
|---|---|---|---|---|
| FLG | Filaggrin — skin barrier structural protein | Ichthyosis Vulgaris | Autosomal Dominant / Semi-dominant | Also strongly linked to atopic eczema via "dual allergen exposure hypothesis" |
| STS | Steroid sulphatase — breaks down cholesterol sulphate | X-Linked Ichthyosis | X-Linked Recessive | Large deletion common. Placental deficiency causes obstetric complications in carrier females. |
| TGM1 | Transglutaminase 1 — crosslinks cornified envelope proteins | Lamellar, Bathing Suit, Self-Healing Collodion | Autosomal Recessive | Most common ARCI gene. Temperature-sensitive variants cause bathing suit phenotype. KB105 targets this. |
| ALOX12B / ALOXE3 | 12R-lipoxygenase / eLOX-3 — lipid synthesis in stratum corneum | Lamellar / ARCI | Autosomal Recessive | Second most common ARCI genes. Some milder cases than TGM1 mutations. |
| NIPAL4 | NIPAL4 — magnesium transporter involved in lipid synthesis | Lamellar / ARCI | Autosomal Recessive | More prevalent in some South Asian populations. Part of the ARCI spectrum. |
| ABCA12 | ABCA12 — lipid transporter critical for lamellar granule function | Harlequin Ichthyosis | Autosomal Recessive | Null mutations cause harlequin phenotype. Hypomorphic mutations cause lamellar. Most severe ichthyosis gene. |
| SPINK5 | LEKTI — protease inhibitor controlling desquamation | Netherton Syndrome | Autosomal Recessive | Loss of LEKTI causes uncontrolled protease activity — trichorrhexis invaginata, atopy, hypernatraemia. |
| GJB2 / GJB6 | Connexin 26 / Connexin 30 — gap junction proteins | KID Syndrome | Autosomal Dominant (gain-of-function) | Gain-of-function mutations. Different GJB2 mutations cause Vohwinkel syndrome. Cancer risk from connexin dysregulation. |
| NSDHL | NAD(P)H sterol dehydrogenase — cholesterol synthesis enzyme | CHILD Syndrome | X-Linked Dominant | Lethal in most males. Females: somatic mosaicism creates unilateral pattern. Topical cholesterol/lovastatin corrects local defect. |
| ERCC2 / ERCC3 | XPD / XPB — nucleotide excision repair helicases | PIBIDS / Trichothiodystrophy | Autosomal Recessive | Same genes cause xeroderma pigmentosum — but TTD mutations cause different conformational change. Surprisingly low skin cancer risk unlike XP. |
| PHYH / PEX7 | Phytanoyl-CoA hydroxylase / PTS2 receptor — phytanic acid alpha-oxidation | Refsum Disease | Autosomal Recessive | Phytanic acid is entirely dietary. Dietary restriction is therapeutic — reduces levels and halts neurological/skin progression. |
Related Guides
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Vitamin D & Ichthyosis
Why thick scaling blocks UV absorption and how to manage deficiency risk — especially for ARCI types (Lamellar, Harlequin, CIE).
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New Classification: Epidermal Differentiation Disorders
What the 2024–2025 reclassification of ichthyoses means for your diagnosis, your medical records, and your treatment pathway.
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Clinical Trials Tracker
Actively recruiting trials, recently completed studies with published results, and a step-by-step guide to enrolling.
How to Get Involved in Research
Registries collect data that powers research. The European ARCI registry and FIRST's US registry are actively recruiting. Registration helps researchers find trial participants and understand disease burden.
European ARCI Registry
Tell your dermatologist you are interested in research. Tertiary centres (GOSH, Northwestern, Yale) are often running observational studies or trials. Being registered with a specialist increases the chance of being contacted for studies.
ISG UK, FIRST, and targeted grants fund researchers working towards treatments and cures. ISG UK funds the ISG Research Prize annually — supporting basic science and clinical research.
Donate to ISG UK