Immunoglobulin G as an innovative neuro-diagnostic agent (NIMOCHIP)


Project title
Immunoglobulin G as an innovative neuro-diagnostic agent (NIMOCHIP)
Project Coordinator
Participant Organization(s)
 
Status
In progress
Start date
03-01-2024
Expected Completion
02-01-2027
 
Abstract
In a number of neurodegenerative diseases (NDs) the production of the anti-neuronal immunoglobulin G (IgG) is a significant feature of the immune-inflammatory process. It was shown that human IgGs may induce diverse physiological effects not only on neurons but also on glial cells of animal origin. Of note, these reactions were only in a few cases explained as an antibody-antigen reaction. We propose a genuinely novel biomedical approach to the use of patient IgGs to induce and study physiological reactions on a standardized cellular test platform for in vitro screening of IgGs from amyotrophic lateral sclerosis (ALS) patients. As a short-term goal, we would like to explore the mechanism(s) of these non-canonical IgG effects. As a long-term goal, we intend to introduce a disruptive molecular diagnostics technology at the cellular imaging level that may allow better therapy follow-up of ALS. This unique approach offers a multipurpose processing of a single sample (patient’s IgGs) activating physiological response markers on cells cultured in a microfluidic lab-on-chip. The chip can provide complex information about multiple cellular signaling processes recorded by: (1) electrophysiology - voltage imaging, (2) calcium imaging, (3) Reactive Oxygen Species (ROS), and (4) intracellular vesicle trafficking. This experimental approach will lead to a clinically relevant technology based on microfluidics and automated on-chip video-microscopy. The multidisciplinary data analysis methodology with machine learning will improve the performance towards diagnosis, prediction, monitoring, intervention and especially the assessment of therapeutic response. The personalized experimental diagnostics designed for ALS should in long term serve a variety of NDs in the particular area of neuroinflammation.