RARE DISEASE
Guillain-Barré syndrome
Guillain-Barré syndrome
Guillain-Barré syndrome
Synonyms: GBS, Guillain-Barré-Strohl syndrome
Synonyms: GBS, Guillain-Barré-Strohl syndrome
Synonyms: GBS, Guillain-Barré-Strohl syndrome
Drug discovery
11
drugs
With orphan designations
Overview
Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy and the most common cause of acute flaccid paralysis worldwide [2][5]. Characterized by ascending paralysis, sensory abnormalities, and autonomic dysfunction, it typically follows infections or vaccinations [5][16]. Diagnosis relies on clinical presentation, cerebrospinal fluid analysis, and nerve conduction studies [6][11]. First-line treatments include IV immunoglobulin (IVIG) and plasma exchange [3][8], with most patients achieving functional recovery despite potential long-term disability [1][16].
Categories: rare neurological diseases
Research Papers
1,580 drug discovery papers about Guillain-Barré syndrome, with 3 first-in-class and 36 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,580 drug discovery papers about Guillain-Barré syndrome, with 3 first-in-class and 36 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-03 | Corrigendum to "Elsberg Syndrome with Albuminocytologic Dissociation - A Guillain-Barré Syndrome Mimic or Guillain-Barré Syndrome Variant?".
[This corrects the article DOI: 10.1177/19418744241233621.].
2026-07-31 | Pyruvate Kinase M2 Upregulation Is Associated With Guillain-Barré Syndrome Risk and Immune Dysregulation: Insights From Mendelian Randomization and the Experimental Autoimmune Neuritis Model.
This study aimed to investigate the potential involvement of pyruvate kinase M2 (PKM2) in the pathogenesis of Guillain-Barré syndrome (GBS). Mendelian randomization (MR) analysis was used to evaluate the causal association between PKM2 expression and GBS susceptibility, with mediation analysis performed to explore immune cell-mediated pathways. The association between PKM2 methylation and GBS risk was further examined using GoDMC mQTL data and GRT-qPCRWAS Data Hub profiling. To validate these findings experimentally, an experimental autoimmune neuritis (EAN) mouse model was established in male C57BL/6 mice (6-8 weeks) by immunization with P0180-199 peptide, with tissues collected at disease initiation (Day 8) and peak stage (Day 16). PKM2 expression dynamics, Th17/Treg (regulatory T cells) balance, and histopathological changes were assessed using, Western blot, immunohistochemistry, immunofluorescence, flow cytometry, and H&E/Luxol fast blue (LFB) staining. MR analysis revealed that elevated PKM2 expression in the tibial nerve was significantly associated with an increased risk of GBS (OR: 1.75-6.14, p < 0.05). In the EAN model, PKM2 expression in the sciatic nerve exhibited a time-dependent increase (p < 0.01), primarily localized to inflammatory infiltrates. Mechanistic studies demonstrated that PKM2 upregulation in CD4+ T cells was associated with promoted Th17 differentiation, as evidenced by the upregulation of IL-17a and RORγt (p < 0.05), concomitant with a reduction in Treg cells (p < 0.01). To further elucidate the upstream epigenetic regulation, the association between PKM2 methylation and GBS risk was investigated using GoDMC mQTL data. Among the four selected methylation sites, two-sample MR analyses indicated that cg24327132 were positively associated with GBS risk (p < 0.05). Furthermore, analysis of the GWAS Data Hub revealed that cg24327132 appeared to be preferentially hypomethylated in adaptive immune cells including regulatory T cells, CD4+ T cells, and B cells (Beta ≈ 0-0.05), visually distinct from innate immune populations (Beta ≈ 0.10-0.20), suggesting that perturbation of this hypomethylated state may dysregulate PKM2 expression and contribute to GBS susceptibility. PKM2 upregulation is associated with GBS risk and immune dysfunction. PKM2 methylation may represent a key regulatory mechanism underlying this association. PKM2 may represent a mechanism target warranting further therapeutic investigation.
2026-07-31 | Case Report: Guillain-Barré syndrome mimicking acute brainstem stroke with severe autonomic dysfunction-complete recovery after early plasma exchange.
Acute onset of bilateral ptosis, bulbar palsy, and quadriparesis typically raises suspicion for brainstem infarction. However, when neuroimaging is unrevealing, immune-mediated neuropathies such as Guillain-Barré syndrome (GBS) should be considered. This case highlights the diagnostic challenge and therapeutic response in a seronegative, rapidly progressive GBS variant with severe autonomic involvement. We report a 57-year-old previously healthy man who presented with acute right-sided weakness and dysarthria, progressing over 36 hours to bilateral ptosis, complete ophthalmoplegia, dilated pupils, bulbar palsy, flaccid quadriparesis, urinary retention, and paralytic ileus. Initial brain MRI-DWI was negative. CSF showed no albuminocytologic dissociation. Anti-ganglioside antibodies and neuromuscular junction antibodies were negative. Electromyography revealed motor-predominant polyneuropathy with sympathetic skin response abnormalities. A diagnosis of atypical GBS with severe autonomic involvement was made. Plasma exchange was initiated at 40 hours after onset, followed by a second session on day 5. The patient improved dramatically, walked independently by day 8, was discharged on day 15, and achieved complete recovery at 1 month. This case demonstrates that GBS can present as an acute brainstem stroke mimic with severe ileus and urinary retention, even in the absence of CSF abnormalities or detectable autoantibodies. Early plasma exchange may result in complete neurological recovery. Therefore, clinicians should maintain a high clinical suspicion for immune-mediated neuropathies in patients presenting with rapidly progressive stroke mimics accompanied by autonomic dysfunction.
2026-07-30 | Robot-assisted gait training using a robotic exoskeleton during inpatient rehabilitation in acute Guillain-Barré Syndrome.
A woman in her early 60s with acute Guillain-Barré syndrome (GBS) developed rapidly progressive tetraparesis and respiratory failure requiring non-invasive ventilation. Following intravenous immunoglobulin and medical stabilisation, she entered inpatient rehabilitation with severe weakness, poor truncal control and inability to ambulate. Despite intensive conventional therapy, early gait training was limited. Exoskeleton-based robot-assisted gait training (RAGT) using the Hybrid Assistive Limb (HAL; Cyberdyne Inc, Tsukuba, Japan) was introduced during inpatient rehabilitation as an adjunct to standard therapy. The patient completed 10 HAL sessions over a 15-day period without adverse events. During this time, progressive improvements in ambulatory distance and functional independence were observed. By completion of HAL training, she was able to ambulate 50 m with a walking stick and minimal assistance. She subsequently continued conventional rehabilitation and achieved independent ambulation by discharge. This case suggests that HAL-based RAGT may be a feasible adjunct to inpatient rehabilitation in medically stable patients with acute GBS. The intervention was well tolerated in this patient. Further studies are required to establish patient-selection criteria, optimal timing and the effectiveness of exoskeleton-assisted gait training in GBS.
2026-07-29 | Clinical spectrum and prognostic features of patients seropositive for anti-GD1a antibody.
Anti-GD1a antibodies are associated with a range of immune-mediated neuropathies, particularly acute motor axonal neuropathy (AMAN) and other Guillain-Barré syndrome (GBS) variants. However, their full clinical spectrum and prognostic significance remain unclear due to limited systematic studies. Here, we investigated the clinical phenotypes, serological profiles, cerebrospinal fluid (CSF) characteristic, and therapeutic outcomes associated with anti-GD1a antibodies. The clinical, paraclinical and therapeutic data were retrospectively collected and analyzed from 19 Chinese patients who tested positive for anti-GD1a antibodies. The mean age at onset in this cohort was 50.6 years. Among the 19 patients, 14 (74%) presented with acute syndromes. The remaining five patients (26%) exhibited features consistent with chronic neuropathies. Common manifestations included absent tendon reflexes (84%), limb weakness (84%), sensory impairment (58%), and cranial nerve involvement (53%). Isolated anti-GD1a antibody positivity was observed in only 5 patients, while others had co-existing antiganglioside antibodies, most commonly anti-GQ1b, and anti-GM1. Electrophysiological studies revealed axonal and demyelinating neuropathic patterns. Patients with cranial nerve involvement and albuminocytologic dissociation were associated with higher modified Erasmus GBS Outcome Score (mEGOS). Immunotherapy was effective in acute cases, with 57% achieving complete recovery at 6-month follow-up. Patients seropositive for anti-GD1a antibody exhibits significant clinical and electrophysiological heterogeneity and frequently coexists with other antiganglioside antibodies. Acute presentations generally respond well to immunotherapy, while chronic cases require individualized management.
2026-08-03 | Corrigendum to "Elsberg Syndrome with Albuminocytologic Dissociation - A Guillain-Barré Syndrome Mimic or Guillain-Barré Syndrome Variant?".
[This corrects the article DOI: 10.1177/19418744241233621.].
2026-07-31 | Pyruvate Kinase M2 Upregulation Is Associated With Guillain-Barré Syndrome Risk and Immune Dysregulation: Insights From Mendelian Randomization and the Experimental Autoimmune Neuritis Model.
This study aimed to investigate the potential involvement of pyruvate kinase M2 (PKM2) in the pathogenesis of Guillain-Barré syndrome (GBS). Mendelian randomization (MR) analysis was used to evaluate the causal association between PKM2 expression and GBS susceptibility, with mediation analysis performed to explore immune cell-mediated pathways. The association between PKM2 methylation and GBS risk was further examined using GoDMC mQTL data and GRT-qPCRWAS Data Hub profiling. To validate these findings experimentally, an experimental autoimmune neuritis (EAN) mouse model was established in male C57BL/6 mice (6-8 weeks) by immunization with P0180-199 peptide, with tissues collected at disease initiation (Day 8) and peak stage (Day 16). PKM2 expression dynamics, Th17/Treg (regulatory T cells) balance, and histopathological changes were assessed using, Western blot, immunohistochemistry, immunofluorescence, flow cytometry, and H&E/Luxol fast blue (LFB) staining. MR analysis revealed that elevated PKM2 expression in the tibial nerve was significantly associated with an increased risk of GBS (OR: 1.75-6.14, p < 0.05). In the EAN model, PKM2 expression in the sciatic nerve exhibited a time-dependent increase (p < 0.01), primarily localized to inflammatory infiltrates. Mechanistic studies demonstrated that PKM2 upregulation in CD4+ T cells was associated with promoted Th17 differentiation, as evidenced by the upregulation of IL-17a and RORγt (p < 0.05), concomitant with a reduction in Treg cells (p < 0.01). To further elucidate the upstream epigenetic regulation, the association between PKM2 methylation and GBS risk was investigated using GoDMC mQTL data. Among the four selected methylation sites, two-sample MR analyses indicated that cg24327132 were positively associated with GBS risk (p < 0.05). Furthermore, analysis of the GWAS Data Hub revealed that cg24327132 appeared to be preferentially hypomethylated in adaptive immune cells including regulatory T cells, CD4+ T cells, and B cells (Beta ≈ 0-0.05), visually distinct from innate immune populations (Beta ≈ 0.10-0.20), suggesting that perturbation of this hypomethylated state may dysregulate PKM2 expression and contribute to GBS susceptibility. PKM2 upregulation is associated with GBS risk and immune dysfunction. PKM2 methylation may represent a key regulatory mechanism underlying this association. PKM2 may represent a mechanism target warranting further therapeutic investigation.
2026-07-31 | Case Report: Guillain-Barré syndrome mimicking acute brainstem stroke with severe autonomic dysfunction-complete recovery after early plasma exchange.
Acute onset of bilateral ptosis, bulbar palsy, and quadriparesis typically raises suspicion for brainstem infarction. However, when neuroimaging is unrevealing, immune-mediated neuropathies such as Guillain-Barré syndrome (GBS) should be considered. This case highlights the diagnostic challenge and therapeutic response in a seronegative, rapidly progressive GBS variant with severe autonomic involvement. We report a 57-year-old previously healthy man who presented with acute right-sided weakness and dysarthria, progressing over 36 hours to bilateral ptosis, complete ophthalmoplegia, dilated pupils, bulbar palsy, flaccid quadriparesis, urinary retention, and paralytic ileus. Initial brain MRI-DWI was negative. CSF showed no albuminocytologic dissociation. Anti-ganglioside antibodies and neuromuscular junction antibodies were negative. Electromyography revealed motor-predominant polyneuropathy with sympathetic skin response abnormalities. A diagnosis of atypical GBS with severe autonomic involvement was made. Plasma exchange was initiated at 40 hours after onset, followed by a second session on day 5. The patient improved dramatically, walked independently by day 8, was discharged on day 15, and achieved complete recovery at 1 month. This case demonstrates that GBS can present as an acute brainstem stroke mimic with severe ileus and urinary retention, even in the absence of CSF abnormalities or detectable autoantibodies. Early plasma exchange may result in complete neurological recovery. Therefore, clinicians should maintain a high clinical suspicion for immune-mediated neuropathies in patients presenting with rapidly progressive stroke mimics accompanied by autonomic dysfunction.
2026-07-30 | Robot-assisted gait training using a robotic exoskeleton during inpatient rehabilitation in acute Guillain-Barré Syndrome.
A woman in her early 60s with acute Guillain-Barré syndrome (GBS) developed rapidly progressive tetraparesis and respiratory failure requiring non-invasive ventilation. Following intravenous immunoglobulin and medical stabilisation, she entered inpatient rehabilitation with severe weakness, poor truncal control and inability to ambulate. Despite intensive conventional therapy, early gait training was limited. Exoskeleton-based robot-assisted gait training (RAGT) using the Hybrid Assistive Limb (HAL; Cyberdyne Inc, Tsukuba, Japan) was introduced during inpatient rehabilitation as an adjunct to standard therapy. The patient completed 10 HAL sessions over a 15-day period without adverse events. During this time, progressive improvements in ambulatory distance and functional independence were observed. By completion of HAL training, she was able to ambulate 50 m with a walking stick and minimal assistance. She subsequently continued conventional rehabilitation and achieved independent ambulation by discharge. This case suggests that HAL-based RAGT may be a feasible adjunct to inpatient rehabilitation in medically stable patients with acute GBS. The intervention was well tolerated in this patient. Further studies are required to establish patient-selection criteria, optimal timing and the effectiveness of exoskeleton-assisted gait training in GBS.
2026-07-29 | Clinical spectrum and prognostic features of patients seropositive for anti-GD1a antibody.
Anti-GD1a antibodies are associated with a range of immune-mediated neuropathies, particularly acute motor axonal neuropathy (AMAN) and other Guillain-Barré syndrome (GBS) variants. However, their full clinical spectrum and prognostic significance remain unclear due to limited systematic studies. Here, we investigated the clinical phenotypes, serological profiles, cerebrospinal fluid (CSF) characteristic, and therapeutic outcomes associated with anti-GD1a antibodies. The clinical, paraclinical and therapeutic data were retrospectively collected and analyzed from 19 Chinese patients who tested positive for anti-GD1a antibodies. The mean age at onset in this cohort was 50.6 years. Among the 19 patients, 14 (74%) presented with acute syndromes. The remaining five patients (26%) exhibited features consistent with chronic neuropathies. Common manifestations included absent tendon reflexes (84%), limb weakness (84%), sensory impairment (58%), and cranial nerve involvement (53%). Isolated anti-GD1a antibody positivity was observed in only 5 patients, while others had co-existing antiganglioside antibodies, most commonly anti-GQ1b, and anti-GM1. Electrophysiological studies revealed axonal and demyelinating neuropathic patterns. Patients with cranial nerve involvement and albuminocytologic dissociation were associated with higher modified Erasmus GBS Outcome Score (mEGOS). Immunotherapy was effective in acute cases, with 57% achieving complete recovery at 6-month follow-up. Patients seropositive for anti-GD1a antibody exhibits significant clinical and electrophysiological heterogeneity and frequently coexists with other antiganglioside antibodies. Acute presentations generally respond well to immunotherapy, while chronic cases require individualized management.
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Drug Discovery Landscape
11 orphan drug designations for Guillain-Barré syndrome.
11 orphan drug designations for Guillain-Barré syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Humanised IgG4 monoclonal antibody against C1q | antibodies | EMA | 2023-10-13 | — | Sinclair Regulatory Consulting Europe Limited |
Eculizumab [Soliris] | antibodies | EMA | 2022-10-11 | — | Alexion Europe |
eculizumab | antibodies | FDA | 2022-09-28 | — | Alexion Pharmaceuticals, Inc. |
imlifidase | proteins | FDA | 2018-02-14 | — | Hansa Medical AB |
humanized IgG4 monoclonal antibody binding to human C1q | antibodies | FDA | 2017-01-19 | — | Annexon, Inc. |
Recombinant protein derived from the saliva of the Ornithodoros moubata tick | proteins | EMA | 2016-06-27 | — | Akari Malta Limited |
nomacopan | proteins | FDA | 2016-05-10 | — | Akari Therapeutics Plc |
immune globulin (human) | antibodies | FDA | 2010-03-02 | — | Octapharma USA, Inc. |
Fampridine | small molecules | EMA | 2007-07-10 | — | Ulrich Granzer |
4-Aminopyridine | small molecules | FDA | 2005-12-14 | — | Merz Pharmaceuticals LLC |
Immune Globulin Intravenous (human) | antibodies | FDA | 2004-05-04 | — | ZLB Bioplasma AG |
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