Multiple Sclerosis

Multiple sclerosis (MS) affects 2.5 million people worldwide. The disease involves an immune-mediated process in which an abnormal response of the body’s immune system is directed against the central nervous system (CNS), which is made up of the brain, spinal cord and optic nerves. The exact antigen — or target that the immune cells are sensitized to attack — remains unknown. People with MS typically experience one of different disease courses, which can be mild, moderate or severe (1). MS is currently untreatable but strategies exist which can help modify or slow the disease course, treat relapses, manage symptoms, improve function and safety, and address emotional health.

The neurodegenerative disease multiple sclerosis (MS) involves repeated episodes of inflammation of nervous tissue in areas of the brain‘s white matter in random patches called plaques. This process is followed by destruction of myelin, the fatty covering that insulates nerve cell fibers in the brain and spinal cord, which leaves multiple areas of scar tissue (sclerosis) along the covering of the nerve cells. Damage of myelin results in a slower or blocked neurological transmission of messages, leading to diminished or lost function.

The treatment of MS typically consists of direct symptom management, brief corticosteroid administration for acute exacerbations, and the regular use of disease-modifying drugs such as glatiramer acetate, interferon-β (IFN-β) and natalizumab. These treatments are mostly not effective enough and significant numbers of patients do not respond or develop antibody responses, thereby eliminating the therapeutic benefit. Moreover, patients treated with interferons often experience several side effects. This demonstrates the need for new therapeutic strategies, not only those that may offer greater patient satisfaction such as oral medications and monoclonal antibodies, but also agents intended to promote neuroprotection and neurorepair (e.g. fingolimod).

The Primomed approach

Primomed will aim to confirm the disease modifying potential of a compound blocking a immunological pathway called IL-23 which has shown indications of being involved especially in the on-set of MS (p19 specific inhibition). IL-23 is intimately engaged in the polarization of CD4+ T cells towards pro-inflammatory functions. At the same time the project will test another compound, which blocks CD40. CD40 is a co-stimulatory molecule expressed on professional antigen presenting cells. The interaction of CD40 with its ligand CD154 on T cells induces bi-directional signaling enhancing immune cell effector functions. The function of CD40 in immune regulation suggests that CD40-CD154 interactions may play a role in diseases where anomalous immune responses are a feature, e.g. autoantibody production or chronic inflammation. Blocking the CD40 pathway in multiple sclerosis is expected to interfere with the ongoing inflammatory process and hereby cause a relief of symptoms. Sufficient scientific literature supports this hypothesis.