Therapeutic Monoclonal Antibody Therapies in Chronic Autoimmune Demyelinating Neuropathies

Monoclonal Antibody Therapies

Currently, autoimmune diseases of the peripheral nervous system are mainly treated with exogenous, high-dose intravenous immunoglobulin (IVIg). However, due to the increasing shortage of IVIg and other problems, it is crucial to develop new therapies, one of which is the use of B-cell-depleting monoclonal antibodies. This route has played a prominent role in the treatment of chronic autoimmune demyelinating neuropathies, particularly in anti-MAG antibody neuropathy and autoimmune neuropathies with nodal/paranoid antigen antibodies unresponsive to IVIg.

Features

Specificity-Specific binding, selective target cell killing, targeted distribution in vivo, and enhanced efficacy.
Diversity-Diversity of target antigens, antibody structures,and mechanisms of action.
Targeted-Preparation of antibody drugs with different therapeutic effects according to needs.

Applications

Diagnostic reagents for medical testing
Protein purification
Tumor guidance therapy and radio-immunoimaging technology

Monoclonal Antibody Therapies in CIDP

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a type of inflammatory polyneuropathy characterized by progressive symmetric (lasting more than 2 months) or recurrent remitting sensorimotor deficits. Clinical studies have shown that a patient with CIDP received and responded to rituximab after the failure of IVIg and steroid therapy. In addition, the FcRn blockers efgartigimod (a humanized IgG1-derived Fc fragment that competitively inhibits FcRn) and rozanolixizumab are being investigated in CIDP.

Monoclonal Antibody Therapies in Nodo-Paranodopathies

Nodo-paranodopathies are autoimmune neuropathies. Patients with this disease respond poorly to IVIg and antibodies (mainly IgG4 and IgG3 subtypes) to nodal-paranodal antigens (i.e., neurofascial-155, contactin-1, and caspr1 in the region of the paranodal, and neurofascin-186/-140 in the region of the nodal). Clinical studies have shown that this type of disease appears to respond to rituximab. In addition, one patient responded to daratumumab, an anti-CD38 monoclonal antibody targeting long-lived plasma cells, after the failure of multiple therapies, including steroids, plasma exchange, and rituximab.

Monoclonal Antibody Therapies in Anti-MAG Antibody Neuropathy

Neuropathy with anti-MAG antibodies is the most common IgM paraproteinemic neuropathy and is characterized by predominant sensory symptoms, ataxic gait, and upper limb tremors, with motor involvement and disability occurring late in the course of the disease. Clinical studies have demonstrated that the administration of rituximab improves the disability caused by anti-MAG neuropathy. However, there are very few immunotherapies that are effective in treating anti-MAG neuropathy. Thus, it is necessary to develop monoclonal antibodies that are more effective against B-cell depletion.

Fig 1. Neonatal Fc receptor, complement membrane attack complex (MAC), CD20, and monoclonal antibodies targeting CD20. (Chiara Briani, et al. 2022)

Monoclonal Antibody Therapies in Multifocal Motor Neuropathy

Multifocal motor neuropathy (MMN) is a rare form of acquired motor neuropathy that primarily affects young men and is characterized by progressive asymmetric weakness without sensory loss.

MMN does not respond to steroids or plasma replacement, and the response to IVIg therapy remains unclear. A study indicated that ARGX-117 (an Fc-engineered human IgG1 inhibitory anti-C2 antibody) inhibits C2-dependent complement activation triggered by the binding of IgM anti-GM1 to motor neurons.

Reference

Briani, C.Visentin, A., Therapeutic monoclonal antibody therapies in chronic autoimmune demyelinating neuropathies. Neurotherapeutics, 2022. 19(3): p. 874-884.

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