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).