Definition

Multiple Sclerosis (MS) is a prototypic complex disease in which the immune system launches an autoimmune attack against the brain, resulting in significant disability.

Pathologically, MS is characterized by demyelination, multifocal inflammation, reactive gliosis, and oligodendrocyte and axonal loss. There are four clinical forms of MS: relapsing remitting (RR), secondary progressive (SP), primary progressive (PP), and progressive relapsing (PR) MS.

MS is the second cause of disability in young people in the EU, and it imposes a significant social and health burden to EU citizens and governments.

Causes

The etiology of MS remains elusive; however, it is assumed that both a complex genetic background and environmental factors contribute to disease manifestation.

Symptoms

The symptoms, severity, and course of MS vary widely depending partly on the sites of the plaques and the extent of the demyelination.

Treatment

Current MS therapies are based on the use of immunomodulatory drugs that modulate the interactions between lymphocytes and monocytes, thereby affecting the activity of the adaptive immune system in different ways (the interplay between lymphocytes and monocytes), decreasing cerebral inflammation and damage. MS therapies are divided into three categories: First line therapy that includes different formulations of IFN-beta and GA; second line therapy includes the use of natalizumab and fingolimod; and third line therapy involving chemotherapeutic approaches (mitoxantrone, cyclophosphamide). Although providing comparative estimates of efficacy is difficult, we can estimate that first line therapy reduces relapses by 30-40%, second line therapy by 50-60% and third line therapy by 60-70%. However, such efficacy only considers the reduction in the number of relapses and the prevention of associated disability, without accounting for the progressive phase of the disease, which affects more than half of patients. Moreover, these therapies are associated with significant side-effects, such as adverse immune reactions or severe opportunistic infections, and they therefore require frequent injections. Thus, while the benefits to patients are well established, they are modest and the situation is far from satisfactory. Moreover, current therapies are only effective in a subgroup of patients with relapsing disease, and they only target immune system activation without exerting neuroprotective or regenerative effects.

Given the involvement of multiple signaling pathways in complex diseases like in the case of MS, combining different therapies is a promising strategy, each providing an additive or even synergistic effect in modulating the pathways affected by the disease. However, the challenge of defining combination therapy in drug discovery programs is not insignificant, as the individual and combined effects of each drug in the organism must be identified, as well as possible side-effects due to drug interactions. The combinatorial nature of this approach requires the analysis of a large number of scenarios due to the focus on several targets as opposed to the testing of single drugs, which make it unaffordable from the experimental perspective.


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CONTACT

Albert G. Zamora, Coordinator
Bionure Farma S.L.
Dalmases, 27, Local 1 08017 Barcelona
combims@bionure.com

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