Since the last decade of the 20th century, research in Multiple Sclerosis has grown exponentially, which has led to the introduction of several treatments that have contributed to modify the evolutionary course of the disease, although its cure is still an unfulfilled longing.
In the 50’s of the last century, corticotropin (ACTH) began to be used subcutaneously (s.c.); this drug improved symptoms and the duration of outbreaks. A similar effect is achieved by methylprednisolone, administered at high doses and intravenously (i.v.), which is the drug most commonly used today to treat flare-ups.
Azathioprine, methotrexate and cyclofasfamide, in different doses and in forms of varying severity, have been indicated empirically since the 1980s, taking into account the autoimmune hypothesis as the cause of MS. In 1993, interferon beta 1b via s.c. (Betaferon) began to be used, after demonstrating a disease course-modifying effect by significantly reducing the rate of flares compared to placebo. The demonstration of therapeutic efficacy, following the rules of evidence-based medicine, has since been required for all drugs approved by regulatory agencies. Thus, three years later, interferon beta 1a (Avonex) was introduced intramuscularly; in 1997, glatiramer acetate (Copaxone) became available; in 1998, high-dose interferon beta 1a s.c. (Rebif). All these so-called immunomodulatory drugs are currently considered very safe and with relative efficacy (attenuation of the inflammatory-demilinizing component).
Mitoxantrone was introduced in Neurology in 2000 to treat aggressive forms, but its serious side effects (heart disease and leukemias), together with the approval in 2006 of natalizumab (Tysabri) (humanized monoclonal antibody), meant that it is hardly used today. The considerable efficacy of natalizumab is offset by the increased risk of progressive multifocal leukoencephalopathy, a severe infectious oligodendropathy caused by papovavirus JC. In 2011, fingolimod (Gylenia), an orally administered drug, was approved. Both natalizumab and fingolimod, considered selective immunosuppressants, interfere with the passage into the CNS of activated T lymphocytes, putative main culprits of CNS myelin damage: the former acts by preventing the binding of such lymphocytes to the vascular endothelium by blocking their alpha-4-integrin molecule, while the latter internalizes S1P1 receptors, necessary for their exit from the lymphoid organs.
In the last two years, two new oral immunomodulatory drugs, teriflunomide (Aubagio) and dimethyl fumarate (Tecfidera), and a new monoclonal antibody, alentuzumab (Lemtrada), have been approved. The first two have efficacies at least similar or superior (dimethyl fumarate) to the first-line drugs (interferons and copaxone). Alemtuzumab, which is administered i.v., has at least similar efficacy to first-line drugs (interferons and copaxone). (5-day course per year), binds to the CD52 molecule, present on the surface of leukocytes and monocytes, producing a depletion of T, B and NK cells, which is more intense and sustained with regard to LT-CD4+. This highly effective drug can produce various immunological effects (thyroiditis, thrombocytopenia, glomerulonephritis), which require constant monitoring despite its spaced administration.
In addition to the drugs indicated to modify the course of the disease, others are used to treat associated symptoms: paroxysmal symptoms (carbamazepine and gabapentin), fatigue (amantadine and modafinil), spasticity (botulinum toxin, diazepam, tizanidine, baclofen and cannabidiol), gait claudication (fampridine).
We hope that in the not too distant future there will be drugs that repair axonal damage and have a neuroprotective effect, which will prevent or delay the development of cerebromedullary atrophy, the basis of disability.