Targeting the Type I interferon pathway in Neuromyelitis Optica Spectrum Disorder

点击翻译按钮获取中文摘要

Neuromyelitis Optica Spectrum Disorder (NMO) is a disease of the nervous system which can cause severe disability and blindness. Patients are treated with broad suppression of the immune system. This works for some -but not all- patients. Although we have good drugs, there is currently no way to precisely predict who needs which drug. So the aim of this project is to develop a new way of identifying which patients would benefit from a different, targeted treatment.NMO is caused by a direct antibody attack upon aquaporin-4, a protein found at a high concentration on the surface of brain cells called astrocytes. What's the importance of this? Astrocytes play vital roles in the brain; controlling water balance, supporting efficient communication, and supplying energy to other brain cells. In NMO, the astrocytes die as a result of the antibody attack and cannot perform these roles. This leads to inflammation and ineffective communication in the nerves that supply the arms, bladder, bowels, eyes, and legs. Some patients with NMO have an increased level of a protein called interferon in their blood. Usually this protein is helpful at defending us from viral infections but it has been linked to production of bad disease-causing antibodies, like the antibodies found in NMO patients.We think that interferon levels may provide a way of predicting which patients will respond to targeted immune treatments. Our lab will be working with a state of the art ultra precise way of measuring interferon in patient blood samples. We will use this technique to measure interferon levels in a group of patients from across the UK. Then we will look at how interferon levels relate to the severity of patient disease and the response that people have to treatment.In conjunction with this we will study human immune cells and astrocytes 'in a dish' to try and understand how and why interferon promotes the immune system's attack upon astrocytes. This could help us to find other new targets for medicines.