# Targeting Antigen-Presenting Cells in Multiple Sclerosis Treatment
## 1 Introduction  
Multiple sclerosis (MS) is an autoimmune, inflammatory, and demyelinating disease of the central nervous system (CNS). Its etiology is still unknown, despite the fact that the new concepts appear with more in-depth studies. The pathogenesis is clearer, and we know that pathological processes such as inflammation, demyelination, astrogliosis, and neurodegeneration play an important role in this complex mechanism [1]. For many years, autoimmune inflammation was considered to be the initial step in MS pathogenesis. It is suggested that the major target of autoimmune attack is protein autoantigens localized in the CNS myelin sheaths. This concept was confirmed in animal models of the disease [2]. The complex clinical and pathological picture of MS is not reflected by single animal models. Rather, various animal models are utilized for studies on different aspects of this disease. One of the most frequently used model, especially in the context of autoimmunity, is EAE (_experimental autoimmune encephalomyelitis_). There are two main types of EAE--active and passive--depending on the selected method of induction [3]. Moreover, this model can be induced in various animals, such as mice, rats, guinea pigs, and primates. EAE resembles MS in pathological changes observed in the CNS (inflammation, demyelination, neurodegenerative) and in some aspects of clinical signs [4]. However, the etiology has varied greatly, as EAE is induced by animal immunization with selected myelin peptides, whereas in patients with MS, the autoantigen responsible for disease induction is not known. The clinical picture of MS is also complex. Four different clinical courses of MS can be distinguished. The most common (85%) is the remitting-relapsing type of the diseasecharacterized by the appearance of neurological attacks of the disease. Those attacks are clinical manifestations of acute inflammatory events in the CNS and last at least 24 h [5]. The type of the symptoms depends on the localization of the lesion in the CNS. Generally, those symptoms can be visual, motor, sensory, or cognitive. Relapses are separated by the spontaneous remissions, which are the consequence of healing processes in the CNS. The duration of the remissions is unpredictable and may last weeks, months, or even years. Approximately half of the patients with remitting-relapsing MS will develop the secondary progressive form of MS after 10 years [6]. This is the critical point of the disease, because it represents the situation where neurodegeneration starts to dominate in the CNS over inflammation. In some patients, this situation is present from the beginning of the disease and this is the most serious third clinical course of MS called primary progressive MS. In this variant, the disease constantly progresses without any remissions. The last clinical type of MS is the combination of previous ones whereby the patients experience relapses and progression of the disease. This form is called progressive relapsing MS [7]. Progressive forms of MS are bad predictors for the patients future, because the vast majority of currently available drugs for MS are registered for remitting-relapsing MS. Those treatments target the patient immune system. So far, there are no effective drugs for the treatment of neurodegeneration predominating in progressive MS. Treatment of MS can be divided into: (a) treatment of MS symptoms, (b) treatment of MS relapse, and (c) treatment modifying disease progression. The major goal of MS treatment is slowing down the disease progression. Several medicines have shown to be effective in this area during the last twenty years. The first drugs were beta interferons and glatiramer acetate injected s.c. or i.m. ; later, i.v (natalizumab) and p.o. drugs (fingolimod) were developed. The newer medicines are more effective than the previous ones to diminish relapse rate and slow down MS progression, but they also ameliorate pathological changes seen in MRI of MS patients. The mechanisms of action of disease-modifying treatments in MS are varied.