Table 1.
Drugs approved for the treatment of multiple sclerosis [3]
| Generic name (brand name) | Mechanism of action | Route of administration (dose) | Location of molecular target | Therapeutic efficacy |
|---|---|---|---|---|
| IFNβ-1a (Avonex and Rebif)) | Suppression of Th1 and enhancement of Th2 immune response | Avonex: Once a week, i.m. (30 μg). | Circulating compartment* | Reduced relapse rate (32%) and MRI lesions (circa 80%) |
| Rebif: Three times a week; subcutanous (44 μg) | ||||
| IFNβ-1b (Betaseron and Extavia) | Suppression of Th1 and enhancement of Th2 immune response | Betaseron: Every other day, subcutanous (250 μg). | Circulating compartment | Reduced relapse rate (32%) and MRI lesions (circa 80%) |
| Extavia: Three times a week, subcutanous (250 μg) | ||||
| Glatiramer acetate (Copaxone) | Tolerization with myelin-like antigens and modulation of autoreactive T cells by inducing a shift from Th1 toTh2 cells. | Every day, subcutanous (20 mg) | Circulating compartment | Reduced relapse rate (29%) and MRI lesions (35%) |
| Mitoxantrone (Novantrone) | Inhibition of the proliferation of T cells, B cells and macrophages | Four times a year; intravenous. The lifetime cumulative dose is limited to 8–12 doses over 2–3 years (140 mg). | Circulating compartment | Reduced relapse (67%), and MRI lesions (85%) and disease progression |
| Natalizumab (Tysabri) | A humanized monoclonal antibody to α4β1 integrin that prevents the movement of leukocytes from the bloodstream into the CNS | Every 4 weeks by intravenous infusion (300 mg) | Circulating compartment | Reduced relapse (66%), and MRI lesions (90%) and disease progression |
| Fingolimod (Gilenya/Gilenia) | Reduction in the number of lymphocytes in the blood by preventing their egress from lymph nodes through modulation of the sphingosine-1-phosphate receptor 1. | Every day; oral (0.5 mg) | Circulating compartment | Reduced relapse rate (54%) and MRI lesions (67%) |
| Teriflunomide (Aubagio) | An immunomodulator with anti-inflammatory properties, probably through inhibition of dihydro-orotate dehydrogenase. | Every day; oral (7 or 14 mg) | Circulating compartment | Reduced relapse rate (31%) and MRI lesions |
| Dimethyl fumarate (Tecfidera) | TCA intermediate with immune modulation. Activator of the Nrf2 pathway (the innate cellular phase 2 detoxifying pathway). Nrf2 is: (i) a transcription factor that binds to anti-oxidant response elements and elicits changes in anti-oxidant gene transcription pathway and (ii) Nrf2 has major role in cellular neuroprotective and anti-inflammatory effects | Twice a day, oral (240 mg) | Circulating compartment | Reduced relapse, rate (51%), and new MRI lesions (69%) and disease progression |
*
Blood plasma and lymph fluid. BCNSB, blood–central nervous system barrier; CNS, central nervous system; PNS, peripheral nervous system; Th, T helper cell.