Whether chronic or acute, patients with inflammatory nerve disorders are often out of luck for a quick diagnosis or accurate treatment. A new study could soon contribute to improving the circumstances of these patients though: from the University of Wurzburg, researchers are looking at a specific protein as the culprit for some cases of immune-mediated neuropathy.
Inflammatory nerve disorders develop quickly, often resulting in severe paralysis. There are currently zero diagnostic tests in existence that can accurately diagnose an immune-mediated neuropathies. Patients are then often treated with corticosteroids or antibodies that that have little to no therapeutic effect. Based on results from their current study, published in the journal Brain
, and previous studies with similar findings, Wurzburg scientists recommend a new approach.
In a study of 35 patients with a chronic inflammatory nerve disorder, called chronic inflammatory demyelinating polyneuropathy (CIDP), and 22 patients an acute disorder called Guillain-Barre syndrome, researchers looked for any evidence of autoantibodies targeting a specific component of the nerve fiber called Caspr. This protein helps to build the “Nodes of Ranvier,” a nerve fiber structure that serves as a gap between sections of myelin sheath that forward nerve impulses.
The myelin sheath acts as an “electrical insulator” that propagates nerve impulses to the attached Nodes of Ranvier, and when antibodies attack Caspr, the structure of the nodes is destroyed and nerve function is rendered drastically impaired.
Wurzburg researchers found autoantibodies targeting Caspr in the blood of one patient with CIDP and one patient with Guillain-Barre syndrome. With confirmation of the causation behind these patients’ disease, the researchers successful administered rituximab to inhibit antibody function and reduce the symptoms of their neuropathy. Rituximab is a CD20-directed cytolytic antibody used for treating patients with conditions like non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
Antibodies targeting Caspr proteins may not be the full answer to immune-mediated neuropathies, but researchers from the study believe that antibodies targeting other nerve fiber-related proteins could fill in the gaps of causation. In fact, Caspr is just the third protein in this area of the Nodes of Ranvier for which autoantibodies have been identified. The other two proteins involved with immune-mediated neuropathies include Contactin-1 and Neurofascin-155. Scientists are starting to see that depending on which nerve fiber protein is being targeted by autoantibodies, a patient will exhibit different features.
In the future, researchers plan to conduct blood tests for known autoantibodies that target nerve fiber-related proteins, as well as continue to search for other proteins being targeted that cause neuropathies.
Sources: Therapeutic Advances in Neurological Disorders
, University of Wurzburg
, Basic Neurochemistry: Molecular, Cellular and Medical Aspects. 6th edition