MONOCLONAL ANTIBODIES IN THE TREATMENT OF MULTIPLE SCLEROSIS

Patofi ziologija multiple skleroze tradicionalno uključuje imunološki posredovanu upalnu reakciju središnjeg živčanog sustava, tzv. neuroinfl amaciju, koja je posredovana CD4+ pomoćnim T stanicama tipa 1. Dostupna imunomodulacijska terapija koja je razvijena na temelju ove teorije smanjuje stopu relapsa za otprilike jednu trećinu, ali ne može u potpunosti spriječiti ni relapse ni akumulaciju invaliditeta, te uglavnom nije učinkovita u primarno progresivnom obliku multiple skleroze. B stanice imaju temeljnu ulogu u patogenezi autoimunih neuroloških poremećaja i važni su regulatori procesa aktivacije T stanica, proizvodnje citokina i stvaranja ektopičnih germinalnih centara u središnjem živčanom sustavu. Smatra se da su memorijske B stanice, koje prelaze krvno-moždanu barijeru, podložne ponovljenoj stimulaciji, klonalnoj ekspanziji i diferencijaciji u plazma stanice koje izlučuju protutijela. Posljedično, središnji živčani sustav bolesnika nije samo ciljna meta imunopatološkog procesa, već postaje i mjesto lokalne proizvodnje protutijela. B stanice mogu ili povećati ili ublažiti neuroinfl amaciju, ali u većini bolesnika prevladava proupalni učinak stanica. Deplecija B stanica pomoću humaniziranih monoklonskih antitijela koja prepoznaju specifi čne ciljne antigene, npr. CD20, CD25 ili CD52, je obećavajući terapijski koncept u bolesnika s multiplom sklerozom. Primjena monoklonskih protutijela smatra se gotovo revolucionarnom terapijom i potentna je mogućnost liječenja multiple skleroze, sa snažnim učinkom na progresiju bolesti i dokazanom učinkovitosti u primarno progresivnom obliku bolesti koji se liječi na nezadovoljavajući način.The traditional view of multiple sclerosis (MS) pathophysiology is the immune mediated infl ammation of the central nervous system or so called neuroinfl ammation mediated by type 1 CD4 + auxiliary (helper) T cells. The available immunomodulatory therapy based on this theory reduces the relapse rate by approximately one-third but cannot completely prevent relapses or accumulation of disability and is generally not effective in the primary progressive form of the disease. B cells play a fundamental role in the pathogenesis of various autoimmune neurological disorders and are important regulators of the T cell activation process, cytokine production and formation of ectopic germinal centers in the central nervous system. It is thought that memory B cells, which cross the blood-brain barrier, are susceptible to repeated stimulation, clonal expansion, and differentiation in plasma cells that secrete antibodies. Consequently, the central nervous system is not only the target of the immunopathological process, but also becomes the site of local antibody production. B cells can increase or mitigate neuroinfl ammation, but in most patients, the prophylactic effect prevails. Depletion of B cells by humanized monoclonal antibodies that recognize specifi c target antigens, directed mostly towards CD20 cell antigens, provides a promising therapeutic concept in MS patients. Therapy with monoclonal antibodies has been shown to be a revolutionary and clinically potent treatment for MS, with a strong infl uence on disease progression and proven effi cacy in progressive clinical phenotypes of the disease, currently treated unsatisfactorily. Although approved monoclonal antibodies have proven their effi cacy in MS treatment, the neurologist should keep in mind the potential safety hazards and dangers. Monoclonal antibodies can be used as initial induction MS therapy or chronic maintenance therapy, provided a reliable safety risk management. Treatment needs to be tailored to each individual patient, so neurology increasingly acquires clinical knowledge from oncology or rheumatology, and the focus of action is shifted from diagnosis to extensive clinical treatment. For patients, this means greater availability and wider choice of therapy, but also more intensive and risky medical care experience. The choice of therapy should be adjusted to the risk and benefi t ratio for each patient and regularly monitored via biological markers. The ultimate challenge is to choose an effective and reliable drug for each patient, which will infl uence the development of personalized therapies and personalized neurology that could facilitate the process of therapeutic choice and lead to the best outcome for the patient