Palmoplantar Keratoderma (PPK) is a rare genetic disorder that occurs due to thickening of the skin on the palms and soles. The thickening can be caused by genetic mutations like KRT1, KRT9, GJB2, or even acquired factors. Protheragen has developed preclinical drug and therapy services for PPK, incorporated advanced molecular discovery technologies along with custom disease models to significantly hasten therapeutic advancements.
Overview of Palmoplantar Keratoderma
Hereditary PPK results from mutations to keratin-producing genes KRT1 and KRT9, communication protein GJB2, and desmosomal proteins DSG1. Recent classifications of PPK subtypes are diffuse, focal, and punctate, each with a varying set of genetic and clinical features. The occurrence of hereditary PPK is approximately 1 in every 200,000 to 100,000 individuals, while friction-induced acquired PPK is clinically more common. The cause of this condition occurs from inadequate keratinocyte adhesion, abnormal cornification, and malfunctioning signaling pathways.
Fig.1 AAV-mediated base editing therapy enables to repair effectively the pathogenic gap junction plaques. (Ukaji
et al., 2025)
Diagnostic Development for Palmoplantar Keratoderma
Genetic and Molecular Profiling
Next-generation sequencing panels (NGS) identifying KRT1, KRT9, GJB2, and DSG1 gene mutations can facilitate differential diagnosis of the hereditary PPK subtype through rapid variant assessment. Functional validation of mutations is proven by CRISPR-edited keratinocyte models through assessing keratin death and desmosome degeneration.
Proteomic and Biomarker Analysis
In biopsies of stratum corneum, altered filaggrin degradation products and increased kallikrein activity can be observed in mass spectrometry-based assays and these findings correlate with disease severity. Skin swabs from the lesions are taken and inflammatory cytokines like IL-17, TSLP are measured on Multiplex ELISA platform which helps in monitoring the therapy.
Therapeutics Development for Palmoplantar Keratoderma
The therapeutic research of palmoplantar keratoderma is directed to the management of hyperkeratosis, genetic manipulation of the disorder and inflammation reduction, or pain relief. The further novel strategies are based on the use of gene therapy techniques, focused low molecular weight compounds, and previously approved medicines designed for both the inherited and acquired types of PPK.
Table.1 Therapeutic Development Strategies for PPK. (Bodemer et al., 2025)
| Therapeutic Strategy |
Target |
Key Findings/Mechanism |
Development Stage |
| Local Symptomatic Therapy |
Keratinolytic enzymes, stratum corneum |
Softens hyperkeratosis through keratolysis; regained efficacy with occlusive application. |
Approved |
| Systemic Retinoids |
Retinoic acid receptors (RARs) |
Modulates hyperkeratosis and relieves blistering, albeit desquamation may worsen. |
Approved |
| Gene Therapy |
KRT9, KRT6A, or TRPV3 mutations |
Prevents keratin filament disaggregation through KRT9-linked PPK; epidermolytic PPK models show preclinical efficacy. |
Phase Ib |
| Botulinum Toxin |
Neuromuscular junction (SNAP-25) |
Provides durable efficacy in PC. Stops pain and hyperhidrosis through blockade-induced skin in inflammation. |
Approved |
| Barrier Repair & Anti-Inflammatory |
Filaggrin degradation, JAK-STAT pathways |
Restores the loss of moisture stratum corneum and regulate IL-17/Th2-sustained inflammation in acquired PPK. |
Phase II |
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 comprehensive integrated services for the innovation of palmoplantar keratoderma including the development of therapeutic development, diagnostics development, and disease models to facilitate translation of therapeutic solutions. Via advanced platforms, we guarantee seamless transitions from discovery to IND-enabling studies.
- GJB2 Knockout Cell Lines
- KRT9 Knock-in HaCaT Cells
- Organotypic Co-Culture Systems
- Krt9 p.Leu160Pro Knock-In Mice
- Gjb2 Conditional Knockout Mice
- Dsg1 p.Val9Met Mutant Mice
Protheragen stands out by seamlessly applying advanced in vitro and in vivo technologies to expedite the preclinical development of palmoplantar keratoderma. The integration of our services, such as drug safety evaluation and DMPK, supports the rapid optimization of strategies targeting keratin-stabilizing inflammatory modulators and epidermal barrier restoration for more detailed study.
Partner with us to palmoplantar keratoderma research into viable therapeutic innovations. For inquiries regarding our comprehensive services, please contact us.
References
- Bodemer, C., et al. "Treatment of Hereditary Palmoplantar Keratoderma: A Review by Analysis of the Literature." Br J Dermatol 184.3 (2021): 393-400.
- Ukaji, T., et al. "Aav-Mediated Base Editing Restores Cochlear Gap Junction in Gjb2 Dominant-Negative Mutation-Associated Syndromic Hearing Loss Model." JCI Insight 10.5 (2025).
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
