A bispecific immunotweezer prevents soluble PrP oligomers and abolishes prion toxicity
Fig 6
The bispeficic antibody scPOM-bi prevents the formation of soluble PrP oligomers and protects from prion neurotoxicity even when administered late after infection.
Addition of POM1 antibody (top), but not POM2 or scPOM-bi, to PrPC generates soluble, pK resistant PrP oligomers (red) whose presence correlates with toxicity (top); subsequent addition of the neuroprotective scPOM-bi, but not POM2, eliminates them in favor of larger, non-toxic aggregates (blue). Small soluble oligomers might also be responsible for prion induced toxicity (bottom) similarly to other amyloidosis. scPOM-bi might be able to eliminate them just as it does with the POM1-induced oligomers whereas POM2 might not, which would explain why only the bispecific is neuroprotective even at late administration (21 days post infection, dpi).