A New Bi-dimensional Tool Enhancing the Next Generation of Complement Therapeutics

The new Factor P (Properdin) quantitative and functional assays offer a flexible and complete solution to study properdin.

The Svar solution is a bi-dimensional tool that consists of:

• A high-performing quantitative ELISA for human Factor P that ensures the detection in serum and plasma, giving results in just 2 hours
  
• A functional assay that utilizes the same, high-performing Factor P capture antibody as the quantitative assay and a detection antibody targeting the downstream products of the stabilized C3 convertase to assess the Properdin function.
  

Why look at the Amplification Loop?

The amplification loop is an important contributor to overall complement cascade activity and plays a crucial role in amplifying any small trigger to a bigger downstream response¹. Low-level complement activity is constantly ongoing, especially in the autohydrolysis of the alternative pathway (AP), and the amplifying loop allows mounting a quick response.

The amplification loop comprises a range of components, like Factor B and Factor D, and modulators that are crucial for its functioning and its ability to regulate the overall cascade.
These include inhibitors such as DAF (CD55), Factor H, and Factor I, as well as the only known up regulator, properdin (Factor P), that serves as an amplifier of the alternative pathway, thus making this loop a crucial element in the control of the overall cascade.

Did you know the components of the amplification loop are novel key targets of emerging complement therapeutics?

Complement therapeutics focusing on the amplification loop have the potential to improve disease outcomes and preserve the protective capabilities of the complement system^2-4.

An increasingly popular approach is identifying novel targets to modulate the complement pathways' response rather than completely inhibiting their activity^2,3. The amplification loop - which has often been overlooked in complement therapeutics development - offers a great potential for drug development, as reflected by the current landscape of emerging drugs targeting the alternative pathway to treat a wide range of diseases.

References:

1. Harboe, M. & Mollnes, T. E. The alternative complement pathway revisited. Journal of Cellular and Molecular Medicine 12, 1074–1084 (2008).
2. Harris, C. L. Expanding horizons in complement drug discovery: challenges and emerging strategies. Semin Immunopathol 40, 125–140 (2018).
3. Zelek, W. M., Xie, L., Morgan, B. P. & Harris, C. L. Compendium of current complement therapeutics. Molecular Immunology 114, 341–352 (2019).
4. McNamara, L. A. et al. High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine. 66, (2017).