Olmsted Syndrome (OLMS)
Olmsted syndrome, also known as mutilating keratoderma and periorificial dermatitis, is a rare keratinization disorder that is inherited in an autosomal dominant pattern. The cause of the disease is unknown. Our company is well-equipped to address your drug and therapy development requirements in Olmsted Syndrome therapy.
Background of Olmsted Syndrome
Olmsted Syndrome (OLMS) is an extremely rare genetic disorder characterized by severe palmoplantar and periorificial keratoderma, leading to painful fissures, digital constriction, and autoamputation of digits in severe cases. The exact incidence of OLMS is unclear due to its rarity, but it is considered extremely low worldwide, with only a few hundred reported cases in the medical literature.
Pathogenesis of Olmsted Syndrome
The pathogenesis of OLMS is primarily linked to mutations in the TRPV3 gene, which encodes a transient receptor potential vanilloid-3 ion channel involved in the normal functioning of epithelial cells. These mutations lead to abnormal keratinocyte proliferation and differentiation, resulting in the severe keratoderma characteristic of the syndrome. Recent studies also suggest a possible role of inflammatory pathways contributing to the symptomatology of OLMS, indicating a complex interplay of genetic and possibly immune-mediated factors in its pathogenesis.
Fig. 1 Skin biopsy features. (Choi, J.Y., et al., 2018)Diagnosis Development of Olmsted Syndrome
The diagnosis of Olmsted Syndrome has evolved with advancements in genetic testing, which now plays a crucial role in identifying the disorder. Sequencing of the TRPV3 gene to detect mutations provides a definitive diagnosis, distinguishing OLMS from other similar keratinization disorders.
Therapy Development of Olmsted Syndrome
For instance, Retinoids such as Acitretin are used to treat skin hyperkeratosis by normalizing the growth of skin cells. Additionally, mTOR inhibitors like Sirolimus can regulate cellular proliferation and growth, potentially controlling keratinocyte hyperproliferation, which could be advantageous for OLMS individuals.
CRISPR/Cas9 gene-editing technology could potentially be employed to correct mutations in the TRPV3 gene, implicated in some OS cases. Antisense Oligonucleotides (ASOs) are designed to modulate gene expression and could potentially restore normal function in affected keratinocytes.
Mesenchymal Stem Cells (MSCs) can modulate immune responses and aid tissue repair. Although not yet utilized in OS, they represent a potential pathway for reducing inflammation and promoting skin healing. Fibroblast transplantation is another potential therapy, which might improve skin barrier function and reduce keratoderma.
IL-17 inhibitors such as Secukinumab target the IL-17 pathway and could help alleviate the severe inflammation observed in OS individuals. TNF-alpha inhibitors like Infliximab might manage skin inflammation effectively due to their role in moderating immune responses in dermatological conditions.
Our Services
Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative Olmsted Syndrome therapy strategies and ensure robust support throughout the process.
Platforms of Olmsted Syndrome Therapy Development
Animal Models of Olmsted Syndrome
We have established expertise in developing and utilizing relevant animal models that closely mimic the disease characteristics and response to therapy. These models enable us to evaluate the safety and efficacy of potential therapies.
| Non-Genetically Engineering Models | ||
| We provide diverse model choices customized to meet specific research needs related to Olmsted Syndrome. These models allow researchers to simulate and study the complex biological processes associated with Olmsted Syndrome. | ||
| Optional Models |
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| Genetically Engineered Models | ||
| Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in human Olmsted Syndrome. | ||
| Optional Models |
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| Optional Species | Mice, Rats, Non-human primates, Others | |
In addition to these models, our comprehensive services encompass other models that target specific signaling pathways and molecular targets.
If our services align with your goals, please contact us for more details.
References
- Choi, J.Y., et al., "Olmsted Syndrome Caused by a Heterozygous p.Gly568Val Missense Mutation in TRPV3 Gene." Yonsei Med J, (2018). 59(2): p. 341-344.
- Danso-Abeam, D., et al., "Olmsted syndrome: exploration of the immunological phenotype." Orphanet J Rare Dis, (2013). 8: p. 79.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.