Acro-Dermato-Ungual-Lacrimal-Tooth Syndrome (ADULT Syndrome) is an extremely rare ectodermal dysplasia characterized by the presence of limbs, skin, nails, lacrimal (tear) ducts, and teeth anomalies. Protheragen provides full, one-stop preclinical drug and therapy development services that help address the challenges associated with ADULT Syndrome.
Introduction to ADULT Syndrome
ADULT Syndrome is an autosomal dominant condition in the ectodermal dysplasia group. It is associated with mutations in the TP63 gene, which is critical for the normal development and maintenance of stratified epithelial tissues. People impacted by ADULT Syndrome often present with limb abnormalities, such as ectrodactyly, disorders in skin structure, such as hypohidrosis, disorders in nail shape (dystrophy), obstruction of the lacrimal ducts (thus having issues with tear drainage), and dental abnormalities, such as, hypodontia or malformed teeth. Due to its rarity, the exact incidence of ADULT Syndrome is not defined, but it is viewed as so rare that only a handful of cases have been reported across the world.
Fig.1 The hands and feet of the patient. (Zhou, J.,
et al., 2023)
Biomarkers Development for ADULT Syndrome
- Genetic Biomarkers: Pathogenic TP63 variants (i.e. missense mutations in the DNA-binding domain) remain the gold standard for diagnosis. Recent investigations have discovered novel TP63 splice-site mutations associated with more severe phenotypes.
- Protein Biomarkers: Dysregulated p63 isoforms in patient-derived keratinocytes (ΔNp63α vs. TAp63) correlate with severity of ectodermal defects. Studies are looking into the levels of epithelial-derived proteins (e.g. KLK5, MMP9) in serum as non-invasive biomarkers.
- Multi-Omics Signatures: Proteomic-transcriptomic integrated analyses demonstrated increased KRT17 expression and decreased EDARADD in ADULT tissues, which could be used to distinguish ADULT and Rapp-Hodgkin syndrome.
Therapeutics Development for ADULT Syndrome
Gene & Cell-Based Therapeutics
Cutting edge approaches, such as CRISPR/Cas9-mediated TP63 gene correction and AAV-driven gene replacement, have shown promise in preclinical studies of ADULT Syndrome. Epithelial progenitors derived from induced pluripotent stem cells (iPSCs) and 3D organoid platforms are being utilized to restore lacrimal gland function and epidermal integrity, and studies have shown engraftment in TP63 mice on these models.
Targeted Molecular & RNA Therapeutics
Small molecule directed to modulate TP63 downstream pathways and mRNA therapeutics delivering functional TP63 transcripts are being optimized to restore haploinsufficiency. New peptide inhibitors sought by targeting pathogenic p63 isoforms (ΔNp63α) and mRNA formulations encapsulated in lipid nanoparticles have restored more than 70% target protein in ex vivo patient-derived keratinocytes.
Our Services
Protheragen offers a full range of services to advance therapies for ADULT Syndrome. Our team of expert scientists, dermatologists, and geneticists applies cutting-edge technologies to drive progress, with focused therapeutic development and disease model development services to support your projects.
Therapeutics Development Platforms for ADULT Syndrome
Disease Models Development for ADULT Syndrome
Protheragen's preclinical solutions for ADULT Syndrome are designed to accelerate the translation of groundbreaking therapies from bench to bedside. Our in vitro studies leverage proprietary 2D cell models and 3D skin models to dissect TP63-driven molecular pathologies, including ectodermal differentiation defects and epithelial-mesenchymal dysregulation.
For in vivo validation, we employ genetically engineered murine models and humanized xenograft platforms that faithfully replicate ADULT-specific phenotypes, such as nail dysplasia and lacrimal duct atrophy. These models undergo rigorous phenotypic and molecular validation to ensure clinical relevance.
2D Cell Models & 3D Skin Models
- Patient-Specific Keratinocyte Lines
- ΔNp63α overexpression iPSC
- ADULT Epidermal Organoids
- TP63-deficient 3D models
Animal Models Development
- Conditional TP63 Knock-In Mice
- Tamoxifen-Inducible ΔNp63α Mice
- Humanized ADULT Keratinocyte Xenografts
By integrating gene-edited disease models, multi-omics analytics, and high-throughput screening, we deliver actionable insights to de-risk your therapeutic development pipeline. Contact us to explore how our end-to-end preclinical expertise can advance your ADULT syndrome research.
References
- Whittington, A., S. Stein, and B. Kenner-Bell. "Acro-Dermato-Ungual-Lacrimal-Tooth Syndrome: An Uncommon Member of the Ectodermal Dysplasias." Pediatr Dermatol 33.5 (2016): e322-6.
- Zhou, J., et al. "Case Report: Adult Syndrome: A Rare Case of Congenital Lacrimal Duct Abnormality." Front Genet 14 (2023): 1150613.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
