Soluble Nogo-A, an inhibitor of axonal regeneration, as a biomarker for multiple sclerosis

Background: CNS axons display a poor regenerative response to injury. In multiple sclerosis ( MS), failure of damaged axons to regenerate may be a major factor underlying non-reversible neurologic dysfunction. Nogo is a development-related molecule inhibiting axonal regeneration and is a major component of CNS myelin. Methods: CSF from 114 patients with remitting relapsing MS ( RR-MS) and secondary progressive MS (SP-MS) and 153 controls, as well as CNS tissue from 3 patients with MS and 2 controls, were used for this study. Results: We found soluble 20 kDa Nogo-A product in 96% (110/114) of CSF samples from patients with MS compared with 0/18 from meningo-encephalomyelitis, 0/125 from control subjects with other neurologic diseases, and 0/10 from CNS autoimmune diseases. Nogo-A products were present both in RR-MS and SP-MS, as well as in early cases of the disease, but not in neuromyelitis optica. The same Nogo A product was detected in CNS tissue from all patients with MS but not in control CNS tissue. Conclusion: Soluble Nogo-A may be specific for the CSF of patients with multiple sclerosis and its presence may predict failure of axonal regeneration within the CNS.