Cockayne Syndrome (CS)
Cockayne syndrome is a rare autosomal recessive disorder caused by defects in DNA repair, leading to multi-system degenerative damage. It is primarily characterized by growth retardation, premature aging, photosensitivity, and microcephaly. Our company is well-equipped to address your drug and therapy development requirements in Cockayne Syndrome therapy.
Introduction to Cockayne Syndrome
Cockayne Syndrome is a rare autosomal recessive disorder characterized by growth failure, progressive neurological dysfunction, premature aging, and extreme photosensitivity. The syndrome results from mutations in the ERCC6 (CSB) or ERCC8 (CSA) genes, which impair the transcription-coupled nucleotide excision repair (TC-NER) pathway, crucial for DNA repair. The prevalence of CS is approximately 1 in 200,000 births in European countries.
Pathogenesis of Cockayne Syndrome
The pathogenesis of CS involves mutations in the ERCC8 and ERCC6 genes, encoding Cockayne syndrome proteins A (CSA) and B (CSB), respectively. These mutations disrupt transcription-coupled nucleotide excision repair (TC-NER), leading to accumulation of DNA damage. CSB also plays roles in mitochondrial function, telomere maintenance, and p53 regulation, contributing to the disease's complexity and severity.
Fig. 1 Schematic representation of Cockayne syndrome protein B (CSB) structure. (Wang, A., et al., 2014)Molecular Diagnosis of Cockayne Syndrome
- Next-Generation Sequencing (NGS): This method involves comprehensive analysis of the individual's genome to detect mutations in the ERCC6 and ERCC8 genes, including point mutations, insertions, and deletions. The high throughput and sensitivity of NGS make it an effective tool for diagnosing CS.
- Multiplex Ligation-dependent Probe Amplification (MLPA): MLPA is used to detect multiple sites within the genome, particularly useful for identifying large-scale gene rearrangements and deletions. This method is advantageous for detecting structural variations related to CS.
- Therapeutics Development of Cockayne Syndrome
Small molecule drugs target specific pathways affected by CS to modulate biological processes and alleviate symptoms. Nicotinamide riboside (NR) supplementation has shown promise in improving cellular function in models of DNA repair-deficient diseases like CS.
Monoclonal antibodies (mAbs) target specific proteins involved in CS, potentially correcting or mitigating cellular dysfunctions. Anti-Inflammatory mAbs, targeting inflammatory cytokines like IL-6 to reduce systemic inflammation and related damage in CS individuals.
Gene therapies correct the genetic mutations causing CS by introducing functional copies of the defective genes or editing the genome. CRISPR/Cas9 allows precise genome editing to correct mutations in ERCC6 (CSB) and ERCC8 (CSA) genes, offering hope for a potential cure.
Cell therapies involve transplanting healthy cells to replace or repair damaged tissues in CS individuals. For example, Mesenchymal Stem Cells (MSCs) transplantation has shown improvements in tissue repair and symptom reduction in animal models of CS.
Our Services
Our company embraces a partnership-driven approach. We work closely with clients to develop customized, innovative Cockayne Syndrome therapy strategies and provide strong support throughout the process.
Platforms of Cockayne Syndrome Therapy Development
Animal Models of Cockayne Syndrome
We possess established expertise in developing and using animal models that accurately replicate the disease characteristics and therapeutic responses. These models allow us to assess the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We offer a variety of models tailored to specific research needs related to Cockayne Syndrome. These models enable researchers to simulate and investigate the complex biological processes involved in Cockayne Syndrome. | ||
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| Genetically Engineered Models | ||
| Our proficiency in genetic engineering techniques, including CRISPR/Cas9 technology, enables us to create precise and reliable models that replicate the genetic alterations seen in Cockayne Syndrome. | ||
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| Optional Species | Mice, Rats, Non-human primates, Others | |
Additionally, we can offer other comprehensive Animal models services that focus on specific signaling pathways and molecular targets.
If our services interest you, please contact us at your earliest convenience for more details.
References
- Spyropoulou, Z., et al., "Cockayne Syndrome Group B (CSB): The Regulatory Framework Governing the Multifunctional Protein and Its Plausible Role in Cancer." Cells, (2021). 10(4).
- Karikkineth, A.C., et al., "Cockayne syndrome: Clinical features, model systems and pathways." Ageing Res Rev, (2017). 33: p. 3-17.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.