Anti-MAG Neuropathy

"Anti-myelin-associated glycoprotein (anti-MAG) neuropathy is a rare dysimmune peripheral neuropathy, most commonly associated with an IgM monoclonal gammopathy. Its course is generally slow but may lead to significant functional disability. Despite therapeutic advances, including rituximab, intravenous immunoglobulins (IVIg), immunochemotherapy, and more recently Bruton tyrosine kinase inhibitors (BTKi), treatment response remains highly variable between patients. The Terminal Latency Index (TLI), an electrophysiological parameter reflecting distal demyelination, is a recognized diagnostic marker of anti-MAG neuropathy. However, its potential role as a predictive biomarker of treatment response remains insufficiently studied. Identifying a simple, reproducible, and readily available biomarker that could predict treatment response would be of major clinical importance for personalized patient management and optimization of therapeutic strategies. This monocentric retrospective study will analyze clinical, biological, and electrophysiological data from patients with anti-MAG neuropathy followed at Nice University Hospital (CHU de Nice) to assess the predictive value of baseline TLI for clinical response 12 months after treatment initiation."

The project aims to perform both conventional nerve-conduction studies and axonal-excitability assessments using the TRONDF protocol in patients with selected forms of Charcot-Marie-Tooth disease, with comparison to individuals affected by dysimmune, acquired neuropathies, specifically chronic inflammatory demyelinating polyneuropathy (CIDP) and anti-MAG-neuropathy. The study further includes the analysis of nerve fibers obtained from skin biopsy in patients with CMT, as well as ultrasound evaluation of nerves (from the wrist to the axilla) and of intrinsic hand muscles. Axonal-excitability techniques involve the delivery of two electrical stimuli to the nerve under investigation; both stimuli vary in intensity, whereas only the first, known as the conditioning stimulus, varies in duration. Changes in response amplitude are then measured as these stimulation parameters are systematically adjusted. Some preliminary studies have already suggested the effectiveness of this method in distinguishing CMT1A from certain forms of acquired demyelinating disease, including acute inflammatory demyelinating polyradiculoneuropathy (AIDP) and CIDP. Despite the promising results, only a limited number of studies have so far been conducted in humans and mice, and no comprehensive and systematic study has yet been carried out describing the changes in axonal excitability in the various CMT subtypes, either in humans or in mouse models.

Anti-MAG neuropathy is a progressively disabling orphan rare disorder due to a monoclonal immunoglobulin M(IgM) gammopathy displaying reactivity toward MAG, a glycoprotein of the peripheral nervous system. Its prevalence is around 1/100000 and to date, no treatment has proven efficacy in this disease, including rituximab in 2 Randomized Controlled Trails(RCTs).