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 1 Completed — Phase 2 Paediatric (2026)
Recombinant HSV-1 vector delivering functional TGM1 gene directly to keratinocytes. Phase 1 confirmed correct TGM1 protein expression, functional activity, no immune response, and no vector shedding. IGA improvement at treated sites vs placebo. Paediatric Phase 2 expansion (JADE-1) expected to initiate 2026. FDA Rare Pediatric Disease Designation granted. Most advanced gene therapy for any ichthyosis type.
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)
Real-World Evidence — 98 patients (BJD 2025)
Real-world cohort of 98 patients (BJD 2025, PMID 39470394): 46% were overall responders; best results in Netherton syndrome and CIE with erythrodermic forms. Works primarily on the atopic/inflammatory component — ichthyosis linearis circumflexa may persist. Evidence now extends to infants from 9 weeks old. Currently off-label in UK for ichthyosis — discuss with specialist.
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: Lamellar Ichthyosis (ARCI), X-Linked Ichthyosis
Phase 2/3 Completed
Retinoic acid metabolism inhibitor — increases endogenous retinoic acid without direct retinoid administration. Phase II/III RCT (BJD 2014, PMID 24102348) was conducted in moderate/severe lamellar ichthyosis: 75mg and 150mg once daily improved scaling and DLQI vs placebo. Primary endpoint did not reach statistical significance due to early termination (small sample), but positive trend. Available via named-patient mechanism in some countries. Off-label use in X-linked ichthyosis also reported.
TMB-001 (Topical Isotretinoin 0.05%)
Timber Pharmaceuticals
Target: Congenital Ichthyosis (ARCI + X-linked)
Phase 3 Failed — August 2024
Phase 3 ASCEND trial (NCT05295732) did not meet its primary or key secondary endpoints. The trial enrolled 209 participants (≥6 years, moderate-to-severe ARCI/XLRI). Failure was driven by an unexpectedly high vehicle response rate, not drug toxicity. The Phase 2b CONTROL results (PMID 36794376, 100% VIIS-50 vs 40% vehicle) remain scientifically valid but did not predict Phase 3 outcome. Timber Pharmaceuticals filed Chapter 11 bankruptcy; LEO Pharma acquired the programme in January 2024. TMB-001 will not proceed to regulatory submission.
Abrocitinib (JAK1 inhibitor)
Pfizer
Target: Netherton Syndrome (off-label)
Case Reports — Emerging Evidence
JAK1 inhibitor abrocitinib (approved for atopic eczema) showed marked improvement after 6 months in a Netherton patient (PMID 40159127, 2025), with significant reduction in skin rash and disease severity. Represents an additional oral therapeutic option alongside dupilumab for SPINK5-sEDD/Netherton — discuss with specialist.
Tralokinumab (Adtralza)
LEO Pharma
Target: Lamellar Ichthyosis (off-label, IL-13 blockade)
Case Report — First Use in LI
First published use of anti-IL-13 in lamellar ichthyosis: a man in his 30s treated with tralokinumab + acitretin showed clinically meaningful improvement (JAMA Dermatology 2024, PMID 39382885). Suggests IL-13 pathway involvement in some lamellar ichthyosis subtypes. Currently off-label.
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.
2024
International guidelines updated — congenital ichthyoses
Two-part consensus guidelines published in BJD (PMID 40156154 + 40190069), covering biologics, JAK inhibitors, neonatal care, eye/ENT complications, heat management, and psychosocial support. The most comprehensive management guidance ever published for ichthyosis.
2025
EDD reclassification — ichthyoses renamed as Epidermal Differentiation Disorders
Four landmark British Journal of Dermatology papers reclassify all ichthyoses and palmoplantar keratodermas under gene-based EDD names (e.g. FLG-nEDD, TGM1-nEDD). Designed to enable precision medicine and targeted clinical trial design.
2024
TMB-001 Phase 3 ASCEND trial fails — setback for congenital ichthyosis
August 2024: Timber Pharmaceuticals / LEO Pharma announced Phase 3 ASCEND trial (NCT05295732, 209 participants) failed to meet primary and key secondary endpoints. An unexpectedly high vehicle response rate negated the treatment signal seen in Phase 2b. Timber filed Chapter 11 bankruptcy; LEO Pharma acquired the assets. A significant setback, but the Phase 2b data continue to inform topical retinoid research for ichthyosis.
2026 (expected)
KB105 Phase 2 paediatric expansion (JADE-1) — TGM1 gene therapy
Krystal Biotech's paediatric Phase 2 expansion of the KB105 gene therapy trial expected to initiate in 2026. FDA Rare Pediatric Disease Designation granted. This could be the first approved gene therapy for any ichthyosis type if successful.
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. |
Global Skin Health Context
Ichthyosis research sits inside a wider global push to treat skin disease as a public health priority. Three developments to know about — they shape where future funding, registries, and rare-disease atlases are heading.
WHO · MAY 2025
WHA78 Skin Disease Resolution
The 78th World Health Assembly formally recognised skin diseases as a global public health priority — committing WHO member states to strengthen policy, resources, and care for people with skin conditions, including rare genetic disorders like ichthyosis.
ILDS · ONGOING
ILDS Skin Disease Atlases
The International League of Dermatological Societies is building a family of global atlases mapping the burden of skin disease. The first — GADA, the Global Atopic Dermatitis Atlas — is led by Prof Carsten Flohr (King's College London) and opens the model for rare-disease atlases to follow.
About the ILDS atlases →NEW · 2026
GDEF — Global Dermato-Epidemiology Forum
A new initiative bringing dermatology, epidemiology, and public health together to strengthen the global evidence base for skin diseases and translate it into policy. Backed by the European Dermato-Epidemiology Network and the EADV Taskforce Epidemiology, with a Seminar Series launching this year.
Related Guides
☀️
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