A sugar-coated strategy to treat a rare neurologic disease provides a blueprint for a decoy glycan therapeutic and a potential vaccine for CoViD-19: An Editorial Highlight for "Selective inhibition of anti-MAG IgM autoantibody binding to myelin by an antigen specific glycopolymer"on https://doi.org/10.1111/jnc.15021.
In a rare neurologic disease known as IgM monoclonal gammopathy the immune system targets a sulfated trisaccharide known as the Human Natural Killer-1 (HNK-1) epitope that comprises a constituent of the myelin sheath known as MAG (myelin-associated glycoprotein). This Editorial highlights a study by Aliu and colleagues in the current issue of the Journal of Neurochemistry, in which the investigators constructed a biodegradable poly-l-lysine backbone with multiple copies of this sulfated HNK-1 trisaccharide. This decoy, poly(phenyl disodium 3-O-sulfo-β-d-glucopyranuronate)-(1→3)-β-d-galactopyranoside, known as PPSGG, removed anti-MAG IgM autoantibodies from the blood, while not activating the immune system. These findings provide a path for the selective removal of a pathogenic set of antibodies that target the myelin sheath resulting in neuropathy. These findings are applicable to a parallel strategy for the generation of polysaccharides similar to those present in the receptor-binding domain of CoViD-19, which might inhibit viral adhesion to its receptor, the angiotensin-converting enzyme-2 (ACE2) protein, thereby impairing cellular uptake of the virus itself. The deployment of complex polysaccharides that mimic actual COVID19 polysaccharides on the spike protein may also provide a feasible structural basis for a vaccine. Carbohydrate mimics, if conjugated to a carrier or backbone, might provoke an immune response to the spike protein. A vaccine that targets critical carbohydrates on COVID19, and then neutralizes the virus would recapitulate a successful strategy employed in other microbial vaccines, like the pneumococcal vaccines and the meningococcal vaccines. These vaccines direct an immune response to complex carbohydrates and successfully prevent life-threatening disease. This paper provides lessons from a rare neurologic disease that may teach us strategies applicable to a global pandemic.