FIGURE 4.

A hypothesis for a regional coefficient of efficacy (CE) after immunotherapy. The regional CE was calculated as a ratio between the antibody availability in the CNS and the level of oligomeric α-synuclein. An expected CE was distributed as follows: spinal cord > hippocampus > forebrain > lower brainstem > midbrain > cerebellum. We observed increased phosphorylation of intracellular α-synuclein in the brain stem (SNc, pontine nuclei, inferior olives), i.e., a region with lower CE (entity 1), but not in the spinal cord, forebrain or hippocampus– regions with higher CE (entity 2) after immunotherapy. We propose that these two entities may represent different stages of the dynamics of α-synuclein clearance after rec47 immunotherapy. While in entity 2 it is possible to already measure GCI reduction and reduction of insoluble α-synuclein, entity 1 may be useful to document preceding events before the actual removal of the toxic α-synuclein species.