Novel assays to study the pathophysiology of antibody-mediated channelopathies of the nervous system

PathAb aims to develop and validate in vitro assays in collaboration with Tzartos NeuroDiagnostics for the characterization of the effector functions of disease-causing antibodies of different neuroimmunological disorders to accurately diagnose and provide an optimal and personalized treatment.

Antibody-mediated autoimmune disorders are chronic, highly debilitating disorders that affect an increasing 2.5% of the general population. In the nervous system, the presence of autoantibodies can result in impairment of nerve conduction and synaptic transmission, translating into symptoms varying from hallucinations and delusions, muscle weakness, cognitive complaints, seizures, breathing difficulties, to comma and even death. These are sometimes difficult to diagnose, resulting in delayed treatment. Current treatment strategies rely mainly on general immunosuppression, associated with delayed and even lack of efficacy in some patients and collateral side effects. 

Antigenic modulation and complement activation are two main autoantibodies-effector functions contributing to these disorders. The novel assays characterizing the pathogenic autoantibodies modulation and complement activation’scapacity in individual patients, developed in this project, will 1) speed up and improve diagnosis and 2) provide guidance on the selection of a treatment strategy with a higher success rate for each individual patient. These will prevent chronification and exacerbation of symptoms, reducing hospitalizations, follow-up visits and long-term workabsences. In the Netherlands in 2020 the mean per-patient annual total cost of illness because of one of these disorders ranged from €14,950 to €44,690 based on production losses due to absenteeism, as well as informal care and total cost of illness.

Deliverables include 1) the development of modulation and complement activation assays for different neuronal surface antigens, 2) test the developed assays in a representative group of patients with antibodies against the selected antigens, 3) correlate the modulation and complement activation capacity to the pathophysiology and 4) define the significance of these on disease severity and treatment response.