The rare genetic condition known as Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome exhibits congenital ectodermal dysplasia, ankyloblepharon (eyelid fusion), severe skin erosions, cleft lip and palate. At Protheragen, pride ourselves in providing preclinical drug and therapy development services from end-to-end to meet the unique challenges of AEC syndrome.
Introduction to AEC Syndrome
Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is a rare autosomal dominant disorder with multiple mutations in a single gene, TP63. It is characterized by ankyloblepharon filiforme adnatum, ectodermal defects and orofacial clefts; the incidence of the condition is estimated to occur in 1 out of every 100,000-200,000 live births. Because of research in the past decade, recent literature has confirmed phenotypic variability, including several cases with life-threatening complications; thus, multidisciplinary care is essential to address cutaneous, ocular, and developmental complications.
Pathogenesis of AEC Syndrome
AEC Syndrome is caused by dominant mutations in the TP63 gene, disrupts epidermal development and barrier function. These mutations (e.g., in the SAM domain of p63) impair keratinocyte differentiation and wound healing, leading to skin fragility, erosions, and chronic inflammation. Dysregulated p63 activity also contributes to ectodermal defects, including hair, nail, and tooth abnormalities, and cleft lip/palate.
Fig.1 Disease models and new approaches to develop effective AEC therapies. (Koch
et al., 2014)
Therapeutics Development for Albinism
Small Molecule Therapies
Recently, small molecules, such as PRIMA-1MET, have demonstrated the ability to restore p53/p63-dependent transcriptional networks in epidermal keratinocytes, providing a partial correction of AEC keratinocyte differentiation defects. Select histone deacetylase inhibitors appear to also restore the expression of ΔNp63α target genes via epigenetic modulation with the possibility of supporting cornified envelope formation and the repair of the epidermal barrier in AEC cellular models.
Gene Therapy
CRISPR-Cas9-mediated homology-directed repair (HDR) has been safety incorporated in AEC patient-derived-induced pluripotent stem cells (iPSCs) to enable the precise repair of pathogenic TP63 mutations (R204W, R304Q) to produce iPSCs that are then able to differentiate into functional epidermal keratinocytes restoring barrier function.
Our Services
Protheragen has the ability to provide complete services to advance the therapy for AEC syndrome. Our expert scientists, dermatologists and geneticists use advanced technology to enable progress in focused therapeutic development and disease model development services to support your initiatives.
Therapeutic Development Platforms for AEC Syndrome
Disease Models Development for AEC Syndrome
Protheragen has a comprehensive provision of preclinical models to facilitate your AEC syndrome translational applied research with advanced platforms of both 2D cell models, 3D skin models and animal models development, which are all ready to model the disease-specific pathologies to expedite therapeutic development.
Animal Models Development
- Trp63L514F/+ Mice
- Conditional ΔNp63α Knockdown Mice
- AEC Keratinocyte Xenografts
- 3D Skin Equivalent Implants
Utilizing both gene edited disease models, multi-omics analytics, and high-throughput, Protheragen provides unique insights that de-risk your development pathway of therapeutic development. Contact us to explore how our end-to-end preclinical expertise can advance your AEC syndrome research.
References
- Koch, P. J., et al. "Modeling Aec-New Approaches to Study Rare Genetic Disorders." Am J Med Genet A 164A.10 (2014): 2443-54.
- Varala, S., et al. "A De Novo Case of Ankyloblepharon, Ectodermal Defects, Cleft Lip/Palate Syndrome with Tp63 Mutation Diagnosed Prenatally." Indian J Dermatol Venereol Leprol (2024): 1-3. Print.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
