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Catastrophic Antiphospholipid Syndrome (CAPS)

Catastrophic antiphospholipid syndrome (CAPS) is a very rare complication encountered in a subset of individuals with antiphospholipid syndrome. Specialized drug and therapy development services are essential to enhance and expedite CAPS research. Our company is well-equipped to address your drug and therapy development requirements in CAPS therapy.

Introduction to Catastrophic Antiphospholipid Syndrome

Catastrophic Antiphospholipid Syndrome is a rare and life-threatening variant of antiphospholipid syndrome (APS), characterized by widespread microvascular thrombosis leading to multiorgan failure. Recent studies underscore its rarity, with an estimated annual incidence ranging from 0.15 to 1.05 cases per million individuals. CAPS presents a significant challenge due to its rapid onset and high mortality rate, necessitating prompt recognition and aggressive therapeutic intervention to improve individual outcomes.

Pathogenesis of Catastrophic Antiphospholipid Syndrome

The pathogenesis of Catastrophic Antiphospholipid Syndrome remains poorly understood due to its rarity. However, it is believed to involve a combination of genetic susceptibility, antiphospholipid antibody (aPL) positivity, and environmental triggers. CAPS is characterized by a 'thrombotic storm,' where a primary thrombophilic risk (genetic susceptibility and aPL positivity) is followed by a secondary inflammatory hit, typically triggered by infections or surgery. This cascade leads to simultaneous local thrombosis and systemic inflammatory response syndrome (SIRS), with excessive cytokine release playing a pivotal role.

The 'two-hit' theory in pathogenesis of catastrophic antiphospholipid syndrome (CAPS).Fig. 1 CAPS: the "two-hit" theory. (Bitsadze, V., et al., 2024)

Diagnosis Development of Catastrophic Antiphospholipid Syndrome

Researchers have been exploring various potential biomarkers that could aid in the early identification of CAPS and differentiate it from other thrombotic disorders. Potential biomarkers include those reflecting endothelial dysfunction and activation, systemic inflammation, coagulation activation, complement activation, and tissue damage. Combining multiple biomarkers into panels or algorithms may enhance diagnostic accuracy, but further validation studies are needed to confirm their utility in practice.

Therapy Development of Catastrophic Antiphospholipid Syndrome

Small Molecule Drugs

Small molecule drugs play a crucial role in managing CAPS by interfering with the coagulation cascade and preventing further clotting. Warfarin, a traditional anticoagulant, inhibits vitamin K-dependent clotting factors, while Rivaroxaban, a direct oral anticoagulant, inhibits Factor Xa without requiring regular monitoring. Hydroxychloroquine also reduces the risk of thrombosis by mitigating platelet aggregation and inflammation.

Cell Therapies

Cell Therapies include manipulating or introducing cells to modulate immune responses. Mesenchymal Stem Cells (MSCs) offer immunomodulatory properties, potentially reducing autoimmunity in CAPS. Research indicates MSCs can alleviate inflammation and improve outcomes in animal models. T-cell therapies, under development, aim to modulate autoreactive T cells that contribute to APS and CAPS pathogenesis.

Monoclonal Antibodies

Monoclonal antibodies target specific proteins involved in CAPS. Rituximab, targeting CD20 on B cells, reduces autoantibody production, offering promise in refractory cases. Eculizumab, inhibiting the cleavage of complement protein C5, prevents downstream clotting and inflammation, showing potential in CAPS management.

Gene Therapies

Gene Therapies aim to correct genetic factors contributing to CAPS. CRISPR-Cas9 technology is being explored to target genes associated with autoimmune responses in APS, offering a potentially curative approach. Viral vector-based gene therapy introduces functional genes to modulate immune responses, though it's still in early stages for APS and CAPS.

Our Services

Our company adopts a partnership-driven approach. We collaborate closely with clients to craft tailored, innovative CAPS therapy strategies and ensure robust support throughout the process.

Platforms of Catastrophic Antiphospholipid Syndrome Therapy Development

Animal Models of Catastrophic Antiphospholipid 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 CAPS. These models allow researchers to simulate and study the complex biological processes associated with CAPS.
Biologics/Chemical Induced Models
Optional Models
  • Antiphospholipid Antibody Injection Model
  • Lipopolysaccharide Induced Model
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 CAPS.
Optional Models
  • Transgenic Models Expressing Human Antiphospholipid Antibodies
  • Knockout Models for Coagulation Regulators
  • Receptor Knockout Models
  • Signaling Molecule Knockout Models
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

  • Bitsadze, V., et al., "Catastrophic Antiphospholipid Syndrome." Int J Mol Sci, (2024). 25(1).
  • Martin, E., et al., "Catastrophic antiphospholipid syndrome in a community-acquired methicillin-resistant Staphylococcus aureus infection: a review of pathogenesis with a case for molecular mimicry." Autoimmun Rev, (2011). 10(4): p. 181-188.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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