Review Article

Multiple Sclerosis and the Blood-Central Nervous System Barrier

Table 1

Drugs approved for the treatment of multiple sclerosis [3].

Brand (and generic) nameMechanism of actionRoute of administration (dose)Location of molecular targetTherapeutic efficacy

IFNβ-1a (Avonex and Rebif) Suppression of Th1 and enhancement of Th2 immune responseAvonex: once a week, i.m. (30 μg).
Rebif: three times a week, subcutaneous (44 μg)
Circulating compartment1Reduced relapse rate and MRI lesions
IFNβ-1b (Betaseron and Extavia) Suppression of Th1 and enhancement of Th2 immune responseBetaseron: every other day, subcutanous (250 μg)
Extavia: three times a week, subcutanous (250 μg)
Circulating compartment Reduced relapse rate and MRI lesions
Glatiramer acetate (Copaxone) Tolerization with myelin-like antigens and modulation of autoreactive T cellsEvery day, subcutanous (20 mg) Circulating compartment Reduced relapse rate and MRI lesions
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 and MRI lesions and disease progression
Natalizumab (Tysabri) A humanized monoclonal antibody to α4-β1-integrin that prevents the movement of leukocytes from the bloodstream into the CNSEvery four weeks by intravenous infusion (300 mg) Circulating compartment Reduced relapse and MRI lesions 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 and MRI lesions
Teriflunomide (Aubagio) An immunomodulator with anti-inflammatory properties, probably through inhibition of dihydroorotate dehydrogenase Every day, oral (7 or 14 mg) Circulating compartment Reduced relapse rate and MRI lesions
Dalfampridine (Ampyra) Potassium channel blockadeTwice a day (10 mg) CNS and PNSImproved walking speed
Nabiximols (Sativex)Cannabinoid CB1 and CB2 receptor agonismOromucosal spray (≤12 sprays per day)CNSReduced spasticity

Blood plasma and lymph fluid. BCNSB: blood-central nervous system barrier; CNS: central nervous system; PNS: peripheral nervous system; Th: T helper cell.