RARE DISEASE
Multifocal motor neuropathy
Multifocal motor neuropathy
Multifocal motor neuropathy
Synonyms: MMN, MMNCB, Multifocal motor neuropathy with conduction block
Synonyms: MMN, MMNCB, Multifocal motor neuropathy with conduction block
Synonyms: MMN, MMNCB, Multifocal motor neuropathy with conduction block
Drug discovery
3
drugs
With orphan designations
Overview
Multifocal Motor Neuropathy (MMN) is a rare, immune-mediated motor neuropathy characterized by asymmetric limb weakness, typically affecting distal upper extremities without sensory loss. Diagnosis relies on electrophysiological evidence of multifocal motor conduction blocks and elevated anti-GM1 IgM antibodies in ~50% of patients [1][7][12]. Unlike ALS, MMN progresses slowly, spares cranial/respiratory muscles, and responds to intravenous immunoglobulin (IVIg) [2][4][16]. Early treatment is critical to prevent axonal degeneration and disability [6][13].
Burden
Progressive weakness leads to impaired dexterity, reduced work capacity, and dependence on long-term IVIg [5][12][16].
Chronic disability (e.g., hand atrophy, gait instability) occurs in 30–40% despite treatment [1][17][20].
Psychological distress from delayed diagnosis (often misdiagnosed as ALS) and treatment costs [4][5][12].
Therapies
IVIg (2 g/kg induction, then 1–2 g/kg every 2–8 weeks) is first-line; improves strength in 60–80% of patients [3][6][8].
Subcutaneous immunoglobulin (SCIg) offers comparable efficacy to IVIg with fewer systemic side effects [5][13].
Avoid corticosteroids/plasma exchange (may worsen symptoms); cyclophosphamide or rituximab used in refractory cases [8][12][18].
Categories: rare neurological diseases
Research Papers
306 drug discovery papers about Multifocal motor neuropathy, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
306 drug discovery papers about Multifocal motor neuropathy, with 2 first-in-class and 4 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-14 | Multifocal motor neuropathy: А literature review and case report
Multifocal motor neuropathy (MMN) is a rare immune-mediated disease of the peripheral nervous system manifesting as progressive asymmetric muscle weakness and motor conduction blocks. This article presents a clinical case of a patient with verified MMN in whom the use of rituximab was not accompanied by clinical improvement and was associated with further progression of paresis. Subsequent administration of intravenous immunoglobulin (IVIG) led to pronounced positive dynamics with an increase in muscle strength and a decrease in the severity of motor deficit. Introduction. MMN is a rare dysimmune neuropathy clinically characterized by asymmetric muscle weakness, atrophy, and fasciculations with absent or minimal sensory impairments. The most significant diagnostic signs include the detection of IgM antibodies to ganglioside GM1 and the registration of motor conduction blocks during electroneuromyographic examination. IVIG is considered the mainstay of pathogenetic therapy for MMN, while the efficacy of other immunomodulatory drugs, including rituximab, remains insufficiently defined. Materials and methods. We analyzed a clinical case of a female patient born in 1961 who was admitted with complaints of increasing weakness in the left hand, clumsiness during movements, and fasciculations in the muscles of the left upper limb. The diagnostic evaluation included a neurological examination, electroneuromyography, ultrasound examination of peripheral nerves and the brachial plexus, as well as magnetic resonance imaging. To clarify the nosological entity of the process, an analysis of the cerebrospinal fluid and a laboratory assessment of anti-GM1 antibodies were performed. Results. The examination revealed motor conduction blocks outside typical compression sites, as well as an elevated titer of anti-GM1 antibodies, which confirmed the diagnosis of MMN. The administration of rituximab, necessitated in part by organizational and economic limitations of therapy, did not lead to clinical stabilization. After transferring the patient to IVIG therapy, clear positive dynamics were noted in the form of reduced severity of paresis and increased muscle strength. Conclusion. The presented clinical observation emphasizes the importance of timely diagnosis of MMN and early initiation of pathogenetic therapy. In this case, the use of rituximab did not provide clinical stabilization, whereas IVIG demonstrated high therapeutic efficacy. Improving the availability of immunoglobulin therapy and physicians’ awareness of MMN is essential to prevent the progression of motor deficit and patient disability.
2026-08-05 | Cladribine treatment in chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: two case reports
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) are immune-mediated peripheral neuropathies that may follow a progressive course and be refractory and poorly tolerated to standard immunomodulatory treatments. Therapeutic options for such patients remain limited. We report two patients with immune-mediated neuropathies—one with typical CIDP and one with MMN—who were treated with low-dose intermittent subcutaneous cladribine. Clinical outcomes were assessed using the Medical Research Council (MRC) sum score and the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Both patients demonstrated clinically meaningful and sustained improvements in muscle strength and functional disability lasting up to 24 months after treatment completion. Cladribine was well tolerated; transient lymphopenia occurred in one patient without serious adverse events. These cases suggest that cladribine may represent a potential therapeutic option for selected patients with CIDP or MMN. Further studies are warranted to confirm efficacy and safety.
2026-07-29 | Revisiting multifocal motor neuropathy: mechanisms, diagnosis and future directions.
Multifocal Motor Neuropathy (MMN) is an immune-mediated, pure motor neuropathy characterized by slowly progressive, asymmetric limb weakness. It predominantly affects men in mid-adulthood and often presents with distal upper-limb weakness, such as wrist or finger drop. Although the disease course is typically chronic, slowly and sometimes stepwise progressive, timely recognition is critical, as early immunotherapy can prevent irreversible axonal loss and long-term disability. This review aims to provide a comprehensive and clinically integrated overview of MMN, spanning pathogenesis, clinical presentation, diagnostic challenges, and current and emerging therapeutic strategies. Emphasis is placed on translating mechanistic insights into practical diagnostic and treatment frameworks, and on identifying priorities for future research. Pathophysiologically, MMN is best understood as an antibody-mediated nodo-paranodopathy. IgM antibodies directed against GM1 gangliosides bind to GM1-enriched domains at the nodes of Ranvier, activate the classical complement cascade, and disrupt sodium channel clustering and axo-glial integrity. The resulting conduction block constitutes the electrophysiological hallmark of the disease and may initially be reversible. Persistent immune-mediated injury, however, can lead to secondary axonal degeneration and fixed disability. While GM1 IgM antibodies are detected in a substantial proportion of patients, seronegativity does not exclude MMN, potentially reflecting mechanistic heterogeneity and/or assay limitations. Diagnosis relies on the combination of a characteristic clinical phenotype and electrophysiological evidence of motor conduction block with preserved sensory conduction. However, conduction block can be difficult to demonstrate because of proximal lesions, temporal dispersion, or superimposed axonal loss, contributing to diagnostic uncertainty. High-resolution nerve ultrasound and magnetic resonance neurography offer valuable complementary information by revealing focal nerve enlargement or plexus abnormalities, though neither technique is independently diagnostic. Intravenous immunoglobulin (IVIg) remains the established standard of care and the only approved therapy, producing rapid but often transient improvement that necessitates individualized maintenance regimens. Subcutaneous immunoglobulin provides an effective long-term alternative for many patients. Conventional immunosuppressants have shown limited efficacy, whereas emerging complement inhibitors targeting upstream components of the classical pathway represent a promising, mechanism-based strategy currently under clinical evaluation. Despite advances, significant gaps remain. Reliable biomarkers to predict treatment response, monitor disease activity, and detect early axonal injury are lacking. Future progress will require integrated translational models, harmonized outcome measures, and well-designed clinical trials to move toward more durable and personalized therapeutic approaches in MMN.
2026-07-28 | Discovery and engineering of novel IgM proteases for the treatment of autoimmune and inflammatory diseases 2253144
Abstract Introduction IgM is a multifunctional immunoglobin that acts as the first line of defense against systemic pathogens. IgM’s multimeric structure, together with its complement binding ability, makes IgM a highly potent inflammation driver. The presence of autoreactive IgM antibodies causing complement dependent damage has been described in inflammatory and autoimmune conditions such as Cold Agglutinin Disease (CAD) and Multifocal Motor Neuropathy (MMN) . For this reason, the development of IgM autoantibodies degrading therapy represents an attractive approach. Methods Employing Seismic’s IMPACT platform and evolutionary screening, we identified several novel and selective IgM proteases. Discovered proteases cleave soluble IgM in plasma and the IgM BCR in B cells from healthy individuals. Results CAD is an autoimmune hemolytic anemia, caused by IgM autoantibodies that bind to red blood cells (RBC), causing agglutination and activate complement cascade resulting in RBC death. Seismic’s IgM protease cleaves RBC bound IgM, preventing agglutination in whole blood from CAD donors, an unmet need not targeted by current approved treatment. In addition, IgM cleavage reduced cold-induced complement deposition on RBC from CAD patients. Conclusion Further engineering and optimization with our IMPACT Platform for the novel proteases is currently under way. Funding Source n/a Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-07-11 | Intravenous immunoglobulin frequency in multifocal motor neuropathy: a retrospective study of nerve conduction outcomes.
In resource-limited rural settings, patients with multifocal motor neuropathy (MMN) often present late due to limited access to neurophysiology services, by which time significant axonal damage may have occurred, rendering them less responsive to immunotherapy-yet this clinically subgroup is consistently underrepresented in randomized controlled trials. In this study, we aimed to examined the impact of intravenous immunoglobulin (IVIg) frequency on electrophysiological changes in such undertreated MMN patients. A retrospective analysis was conducted across three rural medical centers. Patients receiving > 2 IVIg cycles annually were classified as group A, others as group B. Nerve conduction was assessed at baseline, after the first treatment course, and at the final follow-up. Thirty-nine MMN patients initially identified, 11 patients with confirmed conduction block (CB) were included. 27 nerves exhibited definite CB, with 7 (25.9%) in the median nerve, 8 (29.6%) in the ulnar nerve, and 6 (18.5%) in both the tibial and peroneal nerves. The treatment intervals was 4.9 ± 1.8 (range, 2.6 to 8.0) months, The follow-up period was 17.2 ± 3.3 months (range, 12.0 to 21.0). 7 (63.6%) were in group A, while 4 patients (36.4%) were in group B. There was a clear improvement in mRS scores at the last follow-up compared to baseline (z = -2.795, p = 0.007). We compared the variations in distal compound muscle action potential (CMAP) amplitude at baseline and the last follow-up, after adjusting for baseline CMAP amplitude, it showed significantly greater improvements in distal CMAP amplitude in group A versus group B (F = 40.217, P < 0.001; B = 2.881, 95% CI 1.941 ~ 3.821, P < 0.001), with the model accounting for 71.5% of the variance (adjusted R²= 0.715). The number of CBs decreased from 17 to 14 in group A, with no change in group B (p > 0.05). High frequency IVIg treatment may be associated with improved CMAP amplitude and mRS in undertreated MMN patients, suggesting potential benefits that require further validation.
2026-08-14 | Multifocal motor neuropathy: А literature review and case report
Multifocal motor neuropathy (MMN) is a rare immune-mediated disease of the peripheral nervous system manifesting as progressive asymmetric muscle weakness and motor conduction blocks. This article presents a clinical case of a patient with verified MMN in whom the use of rituximab was not accompanied by clinical improvement and was associated with further progression of paresis. Subsequent administration of intravenous immunoglobulin (IVIG) led to pronounced positive dynamics with an increase in muscle strength and a decrease in the severity of motor deficit. Introduction. MMN is a rare dysimmune neuropathy clinically characterized by asymmetric muscle weakness, atrophy, and fasciculations with absent or minimal sensory impairments. The most significant diagnostic signs include the detection of IgM antibodies to ganglioside GM1 and the registration of motor conduction blocks during electroneuromyographic examination. IVIG is considered the mainstay of pathogenetic therapy for MMN, while the efficacy of other immunomodulatory drugs, including rituximab, remains insufficiently defined. Materials and methods. We analyzed a clinical case of a female patient born in 1961 who was admitted with complaints of increasing weakness in the left hand, clumsiness during movements, and fasciculations in the muscles of the left upper limb. The diagnostic evaluation included a neurological examination, electroneuromyography, ultrasound examination of peripheral nerves and the brachial plexus, as well as magnetic resonance imaging. To clarify the nosological entity of the process, an analysis of the cerebrospinal fluid and a laboratory assessment of anti-GM1 antibodies were performed. Results. The examination revealed motor conduction blocks outside typical compression sites, as well as an elevated titer of anti-GM1 antibodies, which confirmed the diagnosis of MMN. The administration of rituximab, necessitated in part by organizational and economic limitations of therapy, did not lead to clinical stabilization. After transferring the patient to IVIG therapy, clear positive dynamics were noted in the form of reduced severity of paresis and increased muscle strength. Conclusion. The presented clinical observation emphasizes the importance of timely diagnosis of MMN and early initiation of pathogenetic therapy. In this case, the use of rituximab did not provide clinical stabilization, whereas IVIG demonstrated high therapeutic efficacy. Improving the availability of immunoglobulin therapy and physicians’ awareness of MMN is essential to prevent the progression of motor deficit and patient disability.
2026-08-05 | Cladribine treatment in chronic inflammatory demyelinating polyradiculoneuropathy and multifocal motor neuropathy: two case reports
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) are immune-mediated peripheral neuropathies that may follow a progressive course and be refractory and poorly tolerated to standard immunomodulatory treatments. Therapeutic options for such patients remain limited. We report two patients with immune-mediated neuropathies—one with typical CIDP and one with MMN—who were treated with low-dose intermittent subcutaneous cladribine. Clinical outcomes were assessed using the Medical Research Council (MRC) sum score and the Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Both patients demonstrated clinically meaningful and sustained improvements in muscle strength and functional disability lasting up to 24 months after treatment completion. Cladribine was well tolerated; transient lymphopenia occurred in one patient without serious adverse events. These cases suggest that cladribine may represent a potential therapeutic option for selected patients with CIDP or MMN. Further studies are warranted to confirm efficacy and safety.
2026-07-29 | Revisiting multifocal motor neuropathy: mechanisms, diagnosis and future directions.
Multifocal Motor Neuropathy (MMN) is an immune-mediated, pure motor neuropathy characterized by slowly progressive, asymmetric limb weakness. It predominantly affects men in mid-adulthood and often presents with distal upper-limb weakness, such as wrist or finger drop. Although the disease course is typically chronic, slowly and sometimes stepwise progressive, timely recognition is critical, as early immunotherapy can prevent irreversible axonal loss and long-term disability. This review aims to provide a comprehensive and clinically integrated overview of MMN, spanning pathogenesis, clinical presentation, diagnostic challenges, and current and emerging therapeutic strategies. Emphasis is placed on translating mechanistic insights into practical diagnostic and treatment frameworks, and on identifying priorities for future research. Pathophysiologically, MMN is best understood as an antibody-mediated nodo-paranodopathy. IgM antibodies directed against GM1 gangliosides bind to GM1-enriched domains at the nodes of Ranvier, activate the classical complement cascade, and disrupt sodium channel clustering and axo-glial integrity. The resulting conduction block constitutes the electrophysiological hallmark of the disease and may initially be reversible. Persistent immune-mediated injury, however, can lead to secondary axonal degeneration and fixed disability. While GM1 IgM antibodies are detected in a substantial proportion of patients, seronegativity does not exclude MMN, potentially reflecting mechanistic heterogeneity and/or assay limitations. Diagnosis relies on the combination of a characteristic clinical phenotype and electrophysiological evidence of motor conduction block with preserved sensory conduction. However, conduction block can be difficult to demonstrate because of proximal lesions, temporal dispersion, or superimposed axonal loss, contributing to diagnostic uncertainty. High-resolution nerve ultrasound and magnetic resonance neurography offer valuable complementary information by revealing focal nerve enlargement or plexus abnormalities, though neither technique is independently diagnostic. Intravenous immunoglobulin (IVIg) remains the established standard of care and the only approved therapy, producing rapid but often transient improvement that necessitates individualized maintenance regimens. Subcutaneous immunoglobulin provides an effective long-term alternative for many patients. Conventional immunosuppressants have shown limited efficacy, whereas emerging complement inhibitors targeting upstream components of the classical pathway represent a promising, mechanism-based strategy currently under clinical evaluation. Despite advances, significant gaps remain. Reliable biomarkers to predict treatment response, monitor disease activity, and detect early axonal injury are lacking. Future progress will require integrated translational models, harmonized outcome measures, and well-designed clinical trials to move toward more durable and personalized therapeutic approaches in MMN.
2026-07-28 | Discovery and engineering of novel IgM proteases for the treatment of autoimmune and inflammatory diseases 2253144
Abstract Introduction IgM is a multifunctional immunoglobin that acts as the first line of defense against systemic pathogens. IgM’s multimeric structure, together with its complement binding ability, makes IgM a highly potent inflammation driver. The presence of autoreactive IgM antibodies causing complement dependent damage has been described in inflammatory and autoimmune conditions such as Cold Agglutinin Disease (CAD) and Multifocal Motor Neuropathy (MMN) . For this reason, the development of IgM autoantibodies degrading therapy represents an attractive approach. Methods Employing Seismic’s IMPACT platform and evolutionary screening, we identified several novel and selective IgM proteases. Discovered proteases cleave soluble IgM in plasma and the IgM BCR in B cells from healthy individuals. Results CAD is an autoimmune hemolytic anemia, caused by IgM autoantibodies that bind to red blood cells (RBC), causing agglutination and activate complement cascade resulting in RBC death. Seismic’s IgM protease cleaves RBC bound IgM, preventing agglutination in whole blood from CAD donors, an unmet need not targeted by current approved treatment. In addition, IgM cleavage reduced cold-induced complement deposition on RBC from CAD patients. Conclusion Further engineering and optimization with our IMPACT Platform for the novel proteases is currently under way. Funding Source n/a Topic Categories Therapeutic Approaches to Autoimmunity (THER)
2026-07-11 | Intravenous immunoglobulin frequency in multifocal motor neuropathy: a retrospective study of nerve conduction outcomes.
In resource-limited rural settings, patients with multifocal motor neuropathy (MMN) often present late due to limited access to neurophysiology services, by which time significant axonal damage may have occurred, rendering them less responsive to immunotherapy-yet this clinically subgroup is consistently underrepresented in randomized controlled trials. In this study, we aimed to examined the impact of intravenous immunoglobulin (IVIg) frequency on electrophysiological changes in such undertreated MMN patients. A retrospective analysis was conducted across three rural medical centers. Patients receiving > 2 IVIg cycles annually were classified as group A, others as group B. Nerve conduction was assessed at baseline, after the first treatment course, and at the final follow-up. Thirty-nine MMN patients initially identified, 11 patients with confirmed conduction block (CB) were included. 27 nerves exhibited definite CB, with 7 (25.9%) in the median nerve, 8 (29.6%) in the ulnar nerve, and 6 (18.5%) in both the tibial and peroneal nerves. The treatment intervals was 4.9 ± 1.8 (range, 2.6 to 8.0) months, The follow-up period was 17.2 ± 3.3 months (range, 12.0 to 21.0). 7 (63.6%) were in group A, while 4 patients (36.4%) were in group B. There was a clear improvement in mRS scores at the last follow-up compared to baseline (z = -2.795, p = 0.007). We compared the variations in distal compound muscle action potential (CMAP) amplitude at baseline and the last follow-up, after adjusting for baseline CMAP amplitude, it showed significantly greater improvements in distal CMAP amplitude in group A versus group B (F = 40.217, P < 0.001; B = 2.881, 95% CI 1.941 ~ 3.821, P < 0.001), with the model accounting for 71.5% of the variance (adjusted R²= 0.715). The number of CBs decreased from 17 to 14 in group A, with no change in group B (p > 0.05). High frequency IVIg treatment may be associated with improved CMAP amplitude and mRS in undertreated MMN patients, suggesting potential benefits that require further validation.
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Drug Discovery Landscape
3 orphan drug designations for Multifocal motor neuropathy, including 1 approved therapy.
3 orphan drug designations for Multifocal motor neuropathy, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Empasiprubart | antibodies | EMA | 2025-06-20 | — | Argenx |
empasiprubart | antibodies | FDA | 2024-06-05 | — | argenx BV |
immune globulin infusion (human) [Gammagard Liquid] | antibodies | FDA | 2006-07-20 | 2012-06-22 | Takeda Pharmaceuticals U.S.A., Inc. |
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