Application of glatiramer acetate to neurodegenerative diseases beyond multiple sclerosis: the need for disease-specific approaches.
Adaptive and innate immunity, if well controlled, contribute to the maintenance of the CNS, as well as to downregulation of adverse acute and chronic neurological conditions. T cells that recognize CNS antigens are needed to activate resident immune cells and to recruit blood-borne monocytes, which act to restore homeostasis and facilitate repair. However, boosting such a T-cell response in a risk-free way requires a careful choice of the antigen, carrier, and regimen. A single vaccination with CNS-derived peptides or their weak agonists reduces neuronal loss in animal models of acute neurodegeneration. Repeated injections are needed to maintain a long-lasting effect in chronic neurodegenerative conditions, yet the frequency of the injections seems to have a critical effect on the outcome. An example is glatiramer acetate, a compound that is administered in a daily regimen to patients with multiple sclerosis. A single injection of glatiramer acetate, with or without an adjuvant, is neuroprotective in some animal models of acute CNS injuries. However, in an animal model of amyotrophic lateral sclerosis, a single injection of adjuvant-free glatiramer acetate is insufficient, while daily injections are not only ineffective but can carry an increased risk of mortality in female mice.Thus, considering immune-based therapies as a single therapy, rather than as a family of therapies that are regimen dependent, may be misleading. Moreover, the vaccination regimen and administration of a compound, even one shown to be safe in humans for the treatment of a particular neurodegenerative disease, must be studied in preclinical experiments before it is tested in a clinical trial for a novel indication; otherwise, an effective drug in a certain regimen for one disease may be ineffective or even carry risks when used for another disorder.
Schwartz
Michal
M
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel. michal.schwartz@weizmann.ac.il
Bukshpan
Shay
S
Kunis
Gilad
G
D000818:Animals; D015551:Autoimmunity; D001921:Brain / Q000276:immunology; D000068717:Glatiramer Acetate; D006801:Humans; D009103:Multiple Sclerosis / Q000628:therapy*; D019636:Neurodegenerative Diseases / Q000628:therapy*; D010455:Peptides / Q000009:adverse effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination
D010455:Peptides; D000068717:Glatiramer Acetate