Harlequin Ichthyosis (HI)
Harlequin ichthyosis is a rare genetic skin disorder affecting newborns, characterized by the presence of hard, thickened skin plates that crack and separate. For advancing and accelerating Harlequin Ichthyosis research, specialized drug and therapy development services are essential. Our company is fully equipped to meet your needs in Harlequin Ichthyosis therapy development.
Introduction to Harlequin Ichthyosis
Harlequin ichthyosis (HI) is a rare and severe genetic disorder characterized by thickened skin with deep fissures, resembling diamond-shaped scales. This autosomal recessive condition is caused by mutations in the ABCA12 gene, leading to defective lipid transport and impaired skin barrier function. The incidence of HI is estimated to be approximately 1 in 300,000 births, with higher prevalence in populations with a higher rate of consanguinity.
Fig. 1 Schematic of known ABCA12 mutations. (Ahmed, H. and O'Toole, E.A., 2014)Pathogenesis of Harlequin Ichthyosis
The pathogenesis of Harlequin Ichthyosis (HI) involves a deficiency in the ABCA12 gene, which is crucial for lipid transport and accumulation in keratinocytes. Severe mutations in ABCA12 disrupt lipid transport and the formation of lipid layers in the skin, leading to a compromised epidermal barrier and defective keratinocyte differentiation. This results in the characteristic hyperkeratosis and ichthyosis phenotype observed in HI.
Fig. 2 The physiological roles of ABCA12 in lipid transportation of epidermal keratinocytes and the speculated ichthyosis pathogenetic mechanisms underlying dysfunction of ABCA12. (Shibata, A. and Akiyama, M., 2015) Diagnosis Development of Harlequin Ichthyosis
Advances in genetic sequencing technologies allow for the precise detection of ABCA12 gene mutations. Whole exome sequencing (WES) and whole genome sequencing (WGS) can accurately identify mutations causing Harlequin Ichthyosis. These methods are useful not only for diagnosis but also for prenatal diagnosis and carrier screening.
Therapy Development of Harlequin Ichthyosis
Retinoids such as acitretin and isotretinoin have been used to treat HI. Acitretin normalizes epidermal differentiation, reducing skin scale thickness and improving flexibility. Ceramide-based creams help restore the skin barrier by replenishing essential lipids, improving hydration, and reducing scaling.
CRISPR/Cas9 allows precise editing of the ABCA12 gene mutations in HI. Preclinical studies have shown gene correction in keratinocytes can restore normal protein function. Additionally, AAVs can deliver a functional ABCA12 gene to restore normal protein levels and improve skin barrier function.
Autologous keratinocyte transplantation involves harvesting, expanding, and grafting keratinocytes from the patient to replenish the defective epidermal layer. Mesenchymal stem cells (MSCs) offer another approach, as they can differentiate into various cell types, including keratinocytes, and help repair damaged skin.
Our Services
Our company embraces a partnership-driven approach. We work closely with clients to develop customized, innovative Harlequin Ichthyosis therapy strategies and provide strong support throughout the process.
Platforms of Harlequin Ichthyosis Therapy Development
Animal Models of Harlequin Ichthyosis
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 Harlequin Ichthyosis . These models enable researchers to simulate and investigate the complex biological processes involved in Harlequin Ichthyosis . | ||
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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 Harlequin Ichthyosis . | ||
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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
- Miao, H., et al., "Inherited ichthyosis and fungal infection: an update on pathogenesis and treatment strategies." J Dtsch Dermatol Ges, (2021). 19(3): p. 341-350.
- Ahmed, H. and O'Toole, E.A., "Recent advances in the genetics and management of harlequin ichthyosis." Pediatr Dermatol, (2014). 31(5): p. 539-546.
- Shibata, A. and Akiyama, M., "Epidemiology, medical genetics, diagnosis and treatment of harlequin ichthyosis in Japan." Pediatr Int, (2015). 57(4): p. 516-522..
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.