Therapeutic Vaccine for Acute and Chronic Motor Neuron Diseases: Implications for Amyotrophic Lateral Sclerosis

• Published in: Proceedings of the National Academy of Sciences - PNAS 2003-04, Vol.100 (8), p.4790-4795
• Main Authors: Angelov, D. N., Waibel, S., Guntinas-Lichius, O., Lenzen, M., Neiss, W. F., Tomov, T. L., Yoles, E., Kipnis, J., Schori, H., Reuter, A., Ludolph, A., Schwartz, M.
• Format: Article
• Language: English
• Subjects: Acute Disease; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - immunology; Amyotrophic Lateral Sclerosis - therapy; Animals; Axotomy; Biological Sciences; Cell Death; Central nervous system; Chronic Disease; Disease Models, Animal; Drug therapy; Facial nerve; Facial Nerve - immunology; Facial Nerve - pathology; Facial Nerve - physiopathology; Female; Glatiramer Acetate; Glutamic Acid - toxicity; Humans; Immunization; Injections; Medical research; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Motor Neuron Disease - genetics; Motor Neuron Disease - immunology; Motor Neuron Disease - therapy; Motor neurons; Motor Neurons - immunology; Motor Neurons - pathology; Motor Neurons - physiology; Multiple sclerosis; Nerve Degeneration - immunology; Nerve Degeneration - pathology; Nerve Degeneration - physiopathology; Nerve Degeneration - prevention & control; Neurodegenerative diseases; Peptides - immunology; Peptides - therapeutic use; Superoxide Dismutase - genetics; Superoxide Dismutase-1; T lymphocytes; Vaccination; Vaccines; Vaccines - therapeutic use
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0530191100

Therapeutic vaccination with Copaxone (glatiramer acetate, Cop-1) protects motor neurons against acute and chronic degenerative conditions. In acute degeneration after facial nerve axotomy, the number of surviving motor neurons was almost two times higher in Cop-1-vaccinated mice than in nonvaccinated mice, or in mice injected with PBS emulsified in complete Freund's adjuvant (P < 0.05). In mice that express the mutant human gene Cu/Zn superoxide dismutase G93A (SOD1), and therefore simulate the chronic human motor neuron disease amyotrophic lateral sclerosis, Cop-1 vaccination prolonged life span compared to untreated matched controls, from 211 ± 7 days (n = 15) to 263 ± 8 days (n = 14; P < 0.0001). Our studies show that vaccination significantly improved motor activity. In line with the experimentally based concept of protective autoimmunity, these findings suggest that Cop-1 vaccination boosts the local immune response needed to combat destructive self-compounds associated with motor neuron death. Its differential action in CNS autoimmune diseases and neurodegenerative disorders, depending on the regimen used, allows its use as a therapy for either condition. Daily administration of Cop-1 is an approved treatment for multiple sclerosis. The protocol for non-autoimmune neurodegenerative diseases such as amyotrophic lateral sclerosis, remains to be established by future studies.