Lamellar Ichthyosis (LI)
Lamellar ichthyosis (LI) is a rare genetic skin disorder present at birth. It is one of three hereditary skin disorders known as autosomal recessive congenital ichthyosis (ARCI). For advancing and accelerating Lamellar Ichthyosis research, specialized drug and therapy development services are essential. Our company is fully equipped to meet your needs in Lamellar Ichthyosis therapy development.
Background of Lamellar Ichthyosis
Lamellar ichthyosis (LI) is a rare genetic skin disorder that presents at birth and continues throughout life. It is characterized by the appearance of a shiny, waxy layer of skin, known as a collodion membrane, which typically sheds within the first two weeks of life, revealing red, scaly skin underneath. The prevalence of LI is approximately 1 in 100,000~200,000 people.
Pathogenesis of Lamellar Ichthyosis
Lamellar Ichthyosis is primarily caused by mutations in the gene encoding transglutaminase 1 (TGM1), an enzyme crucial for the formation of the skin barrier. These mutations lead to defective or insufficient enzyme activity, disrupting the normal formation and shedding of the outer skin layer. This results in the characteristic thick, scaly skin seen in LI patients. The pathogenic mechanism often involves missense mutations that cause misfolding of the enzyme's catalytic core domain, significantly reducing its activity and leading to the manifestations of the disease.
Fig. 1 3D model of TGM1 protein. (Nasser, K.K., et al., 2021)Diagnosis Development of Lamellar Ichthyosis
Next-Generation Sequencing (NGS): The advent of NGS technologies has revolutionized the genetic diagnosis of LI. Whole-exome sequencing (WES) and targeted gene panels allow for the rapid identification of pathogenic variants across multiple genes associated with LI.
Genotype-Phenotype Correlation: Recent research has focused on correlating specific genetic mutations with clinical severity and phenotype. Understanding these correlations helps in predicting disease progression and tailoring personalized therapy plans.
Therapy Development of Lamellar Ichthyosis
Small molecule drugs play a crucial role in treating Lamellar Ichthyosis (LI) by targeting specific molecular pathways involved in the disease. Retinoids, such as Acitretin and Tazarotene, are commonly used for their ability to normalize skin cell growth and differentiation, thereby reducing scaling and improving skin appearance.
Monoclonal antibodies (mAbs) represent a targeted therapeutic approach for modulating specific pathways involved in the inflammatory and immune responses associated with LI. Anti-IL-17 mAbs, like Secukinumab, target interleukin-17 to reduce inflammation and scaling.
Cell therapies offer promising treatment options for LI by focusing on restoring the normal function of skin cells. Mesenchymal Stem Cells (MSCs) and Epidermal Stem Cells can differentiate into keratinocytes and promote wound healing and epidermal regeneration.
Gene therapies hold the potential to correct the underlying genetic defects causing LI, offering a curative approach. CRISPR/Cas9 technology can edit specific mutations in genes like TGM1, demonstrating feasibility in preclinical studies. Gene therapy using lentiviral vectors to deliver a correct copy of the TGM1 gene into keratinocytes has shown promise.
Our Services
Our company embraces a partnership-driven approach. We work closely with clients to develop customized, innovative Lamellar Ichthyosis therapy strategies and provide strong support throughout the process.
Platforms of Lamellar Ichthyosis Therapy Development
Animal Models of Lamellar 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 Lamellar Ichthyosis. These models enable researchers to simulate and investigate the complex biological processes involved in Lamellar 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 Lamellar 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
- Nasser, K.K., et al., "Molecular profiling of lamellar ichthyosis pathogenic missense mutations on the structural and stability aspects of TGM1 protein." J Biomol Struct Dyn, (2021). 39(14): p. 4962-4972.
- Yang, J.M., et al., "Novel mutations of the transglutaminase 1 gene in lamellar ichthyosis." J Invest Dermatol, (2001). 117(2): p. 214-218.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.