Therapeutic vaccine for acute and chronic motor neuron diseases: implications for amyotrophic lateral sclerosis.
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.
Angelov
D N
DN
Department of Oto-Rhino-Laryngology, University of Cologne, D50924 Cologne, Germany.
Waibel
S
S
Guntinas-Lichius
O
O
Lenzen
M
M
Neiss
W F
WF
Tomov
T L
TL
Yoles
E
E
Kipnis
J
J
Schori
H
H
Reuter
A
A
Ludolph
A
A
Schwartz
M
M
D000208:Acute Disease; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D000818:Animals; D019771:Axotomy; D016923:Cell Death; D002908:Chronic Disease; D004195:Disease Models, Animal; D005154:Facial Nerve / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D000068717:Glatiramer Acetate; D018698:Glutamic Acid / Q000633:toxicity; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016472:Motor Neuron Disease / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D009046:Motor Neurons / Q000276:immunology / Q000473:pathology / Q000502:physiology; D009410:Nerve Degeneration / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D010455:Peptides / Q000276:immunology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D014612:Vaccines / Q000627:therapeutic use*
D010455:Peptides; C000606290:SOD1 protein, human; D014612:Vaccines; D018698:Glutamic Acid; D000068717:Glatiramer Acetate; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1