Targeting the lectin pathway
Within the LP, either the sensor molecules MBL, the ficolins 1-3, the collectins 10 and 11 or the serine proteases MASP1 and MASP-2 could serve as potential targets. At this point, no strategies have been developed to target the sensor molecules. However, Omeros has developed the MASP-2 targeting human mAB narsoplimab (OMS721) that is currently used in phase III trials for HSCT-TMA, IgA nephropathy and aHUS and in a phase II trial for lupus and other renal diseases (Medicine). For TMA, the FDA has granted narsoplimab breakthrough designation in patients with persistent TMA as well as orphan drug designation for the inhibition of complement-mediated TMAs and the treatment of HSCT-TMA. Given that narsoplimab is already in clinical trials for diseases in which TMA is a critical disease driver, it might be worth to consider this approach for severe cases of COVID-19 infection (Figure 1).
In addition to MASP-2, a C2-blocking antibody (PRO-02) has been developed by Prothix/Broteio to inhibit the formation of the C4b2b convertase of the LP and the CP and is tested as potential therapeutic approach for ischemia reperfusion injury-mediated disorders and autoimmune diseases (Borosss, Yildiz, Simons, Boon & Hack, 2016).