Cockayne Syndrome (CS) is a rare autosomal recessive condition that presents with growth retardation, signs of premature aging, neurologic degeneration, and photosensitivity. Protheragen provides end to end preclinical drug and therapy development services focused on the molecular complexities of Cockayne Syndrome, and will accelerate your research project via breakthroughs.
Overview of Cockayne Syndrome
Cockayne syndrome is a syndrome caused by pathogenic variants in either the ERCC6 (65% of cases) or ERCC8 (35%), which impairs UV-induced DNA repair and triggers accelerated cellular senescence. The core pathological features of CS include developmental delay, progressive neurodegeneration, cataracts, and photohyper/-sensitivity. Epidemiologic studies estimate a global frequency of about 1 in 500,000, and underdiagnosis of CS is likely due to phenotypic overlap with other progeroid disorders or syndromes.
Pathogenesis of Cockayne Syndrome
Cockayne Syndrome is a disorder caused by defective transcription-coupled nucleotide excision repair (TC-NER) due to variants in the ERCC6 (CSB) or ERCC8 (CSA) genes, which cannot properly resolve DNA lesions that block RNA polymerase II-dependent transcription.
CSB is recruited to sites of enhanced RNA transcription and subsequently presents repair complexes and coordinates chromatin remodeling, using a co-factor, HMGN1-p300. CSA mediates the dynamic ubiquitination and deubiquitination of CSB, which functions to maintain transcriptional resolution of RNA polymerase II. In CS, continued transcriptional arrest promotes cellular senescence, and mitochondrial dysfunction further exacerbates reactions that promote the progeroid/neurodegenerative features.
Fig.1 CSB binding is mechanistically dependent on the physical obstruction of RNA polymerase II progression by DNA lesions. (Vessoni
et al., 2020)
Therapeutics Development for Cockayne Syndrome
Gene Therapy
Current gene editing efforts are focused on restoring TC-NER, with particular interest in addressing ERCC6/ERCC8 mutations. CRISPR base-editing and AAV-mediated gene replacement are showing high efficiency in mutation correction (in patient-derived iPSCs) and rescue from UV-induced defects in preclinical studies.
Small Molecule Drug
Small molecules aim to mitigate downstream consequences of TC-NER failure, such as oxidative stress and cellular senescence. Senolytics clear senescent cells, improving neurobehavioral outcomes in CS mice, while Nrf2 activators (e.g., sulforaphane) enhance antioxidant defenses in patient-derived cells.
Our Services
Protheragen offers a complete range of services to progress therapeutic aims to treat Cockayne Syndrome. Our group of experts, scientists, dermatologists, and geneticists utilize the latest and advanced technologies to ensure progress in your research efforts, we focus on therapeutic development, diagnostics development as well as disease model development.
- ERCC6/ERCC8-Mutant Primary Fibroblasts
- ERCC6−/− or ERCC8−/− Immortalized Fibroblasts
- 3D Skin-Epidermal Equivalents
- Ercc6 Knockout Mice
- Conditional Ercc8 Knockout Mice
Protheragen offers comprehensive preclinical research capabilities aimed at progress in Cockayne Syndrome therapeutics from discovery to preclinical development. Our state-of-the-art facilities and experienced team conduct rigorous in vitro and in vivo studies to evaluate the safety and efficacy of potential therapeutics, ensuring that your drug candidates meet the highest standards.
Partner with us to accelerate your Cockayne Syndrome research and transform therapeutic innovations into effective solutions. If you are interested in our services, please contact us.
References
- Fotopoulou, A., et al. "A Subset of Human Dermal Fibroblasts Overexpressing Cockayne Syndrome Group B Protein Resist Uvb Radiation-Mediated Premature Senescence." Aging Cell 24.3 (2025): e14422.
- Vessoni, A. T., et al. "Cockayne Syndrome: The Many Challenges and Approaches to Understand a Multifaceted Disease." Genet Mol Biol 43.1 suppl. 1 (2020): e20190085.
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
