Therapeutic vaccine for acute and chronic motor neuron diseases: Implications for amyotrophic lateral sclerosis

Abstract

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 Cu͞Zn 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.

Glatiramer acetate fights against Alzheimer’s disease by inducing dendritic-like microglia expressing insulin-like growth factor 1

“…Therapeutic vaccination with GA boosts the protective autoimmunity (13)(14)(15). A single injection of GA is protective in acute models of CNS insults (13,15), whereas in chronic models occasional boosting rather than daily is required for a long-lasting protective effect (14).…”

“…A single injection of GA is protective in acute models of CNS insults (13,15), whereas in chronic models occasional boosting rather than daily is required for a long-lasting protective effect (14). In a model of chronically elevated intraocular pressure, for example, weekly administration of adjuvant-free GA was found to result in neuroprotection (19).…”

“…Here we tested this hypothesis by vaccinating transgenic (Tg) AD (Tg-AD) mice with glatiramer acetate (GA), also known as copolymer 1 (Cop-1), (12). GA can weakly cross-react with CNS-resident autoantigens (13) and can safely simulate the protective and reparative effects of autoreactive T cells (13)(14)(15)(16).…”

Mechanism of Action of Glatiramer Acetate in Treatment of Multiple Sclerosis

“…63 In an animal model of glaucoma, GA reduced loss of retinal ganglion cells without affecting intraocular pressure. 64 GA administration protected motor neurons from acute and chronic degeneration 65 and adoptive transfer of GA-reactive T cells enhanced survival of dopaminergic neurons in a mouse model of Parkinson's disease. 66,67 Thus, GA may exert neurotrophic and/or protective properties in addition to immunomodulatory effects.…”

The immunomodulator glatiramer acetate influences spinal motoneuron plasticity during the course of multiple sclerosis in an animal model

“…Since GA may influence the response of non-neuronal cells in the spinal cord, this drug may affect, to some extent, the synaptic changes induced during the exacerbation of EAE. This hypothesis has been explored in just a few studies dealing with optic nerve injury or glutamate toxicity and in motoneuron disease models (24)(25)(26).…”