Blood–spinal cord barrier (BSCB) and BBB degradation occurs early in ALS, provoking the testing of non-brain penetrant anti-complement drugs, including the C3-blocking linear peptide pegcetacoplan (Apellis) [221], C5-blocking peptide zilucoplan and the anti-C5 mAb ravulizumab [222,223]. Here, C3 is linked to amyotrophic lateral sclerosis.