Schnitzler syndrome is a rare, acquired autoinflammatory disorder marked by chronic hives, swollen lymph nodes, bone pain, fatigue, systemic inflammation, and monoclonal gammopathy. With our company, you gain access to a seasoned and specialized team committed to tackling drug and therapy development challenges specific to Schnitzler Syndrom.
Overview of Schnitzler Syndrome
Schnitzler Syndrome is a rare autoinflammatory disorder characterized by a chronic urticarial rash, intermittent fever, bone pain, and monoclonal IgM gammopathy. Recent literature indicates that the incidence of Schnitzler Syndrome is extremely low, with fewer than 300 reported cases globally. The syndrome primarily affects adults, with a median age of onset around 55 years. While its exact cause is unknown, it is believed to involve dysregulation of the innate immune system.
Pathogenesis of Schnitzler Syndrome
The pathogenesis of Schnitzler Syndrome involves the activation of the NLRP3 inflammasome due to an unknown stimulus. This leads to the cleavage of pro-caspase-1 into active caspase-1, which then activates IL-1β and IL-18. IL-1β contributes tomanifestations such as skin urticarial rash, while IL-18 drives the expansion of B cell clonality and the production of monoclonal antibodies, predominantly IgM kappa.
Fig. 1 Hypothesis of pathogenesis of Schnitzler syndrome. (Chu, C.Q., 2022)
Diagnosis Development of Schnitzler Syndrome
- Proteomics Analysis: While Schnitzler Syndrome is not typically considered a genetic disorder, whole-exome sequencing and whole-genome sequencing are being used to explore its potential genetic background. These methods aim to identify gene mutations or polymorphisms associated with the disease, which may help understand its pathogenesis.
- Cytokine and Inflammatory Mediator Measurement: Studies show that cytokine and inflammatory mediator levels are significantly elevated in Schnitzler Syndrome individuals. Precisely measuring levels of molecules like IL-1β, IL-6, and TNF-α can aid in diagnosis and disease activity assessment.
Therapy Development of Schnitzler Syndrome
Small Molecule Drugs
Small molecule drugs modulate pathways involved in inflammation. Anakinra, an IL-1 receptor antagonist, significantly reduces fever and rash by inhibiting IL-1. Rilonacept acts as a decoy receptor, binding IL-1β and IL-1α, thus preventing their inflammatory effects.
Gene Therapies
Gene therapies aim to correct genetic dysfunctions at the molecular level. CRISPR-Cas9 offers potential for correcting mutations related to Schnitzler Syndrome. Gene silencing techniques like RNAi or antisense oligonucleotides (ASOs) can silence overactive genes, such as those in the IL-1 pathway.
Cell Therapies
Cell therapies involve modifying or utilizing immune cells to counteract disease mechanisms. Regulatory T Cells (Tregs) have immunosuppressive functions and can help control inflammation. Mesenchymal Stem Cells possess anti-inflammatory properties that could reduce inflammation and promote tissue repair.
Monoclonal Antibodies
Monoclonal antibodies target specific molecules in the disease process. Tocilizumab, an IL-6 receptor antagonist, helps manage symptoms when IL-1 inhibitors are insufficient. Rituximab, targeting CD20 on B cells, has been used off-label to treat individuals with significant monoclonal gammopathy.
Our Services
Our company embraces a partnership-driven approach. We work closely with clients to develop customized, innovative Schnitzler Syndrome therapy strategies and provide strong support throughout the process.
Platforms of Schnitzler Syndrome Therapy Development
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.
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Non-Genetically Engineering Models |
| We offer a variety of models tailored to specific research needs related to Schnitzler Syndrome. These models enable researchers to simulate and investigate the complex biological processes involved in the syndrome. |
| Optional Models |
- Complete Freund's Adjuvant (CFA) Model
- Anti-CD20 Monoclonal Antibody Injection Model
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- Lipopolysaccharide (LPS) Injection Model
- IgM Monoclonal Protein Injection Model
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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 human Schnitzler Syndrome. |
| Optional Models |
- IL-1β Transgenic Mice Model
- IL-6 Transgenic Mice Model
- Human IL-6 Transgenic Mice Model
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- NLRP3 Activation Mice Model
- FcγR Knockout Mice Model
- Human Monoclonal Antibody Transgenic Mice Model
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| Optional Species |
Mice, Non-human primates, Rats, Others |
In addition to these models, our comprehensive services include other models that focus on specific signaling pathways and molecular targets.
If our services intrigue you, we encourage you to contact us at your earliest convenience for more details.
References
- Chu, C.Q., "Schnitzler syndrome and Schnitzler-like syndromes." Chin Med J (Engl), (2022). 135(10): p. 1190-1202.
- 24. Gellrich, F.F. and Gunther, C., "Schnitzler syndrome." Hautarzt, (2019).
All of our services and products are intended for preclinical research use
only and cannot be used to diagnose, treat or manage patients.
