Takeda Pharmaceutical Research Articles

Spatial Association Between Gene Expression and Brain Damage in Neuromyelitis Optica Spectrum Disorders (S50.004)

<h3>Objective:</h3> To investigate the spatial association between brain damage and gene expression in NMOSD. <h3>Background:</h3> A former study suggested that typical brain lesions in aquaporin-4 positive Neuromyelitis Optica Spectrum Disorders (AQP4+NMOSD) occur at areas with high AQP4 expression. However, this represents a partial view of both brain damage and NMOSD pathogenesis, since the former also includes atrophy and microstructural abnormalities, and the latter involves other elements of the immune system such as complement and granulocytes. <h3>Design/Methods:</h3> 3.0 and 1.5 T brain MRI scans were acquired from 80 AQP4+NMOSD and 94 controls at two European centers. In patients, brain damage was assessed through (i) T2-hyperintense lesion probability map, (ii) white (WM) and grey matter (GM) atrophy at voxel-based morphometry on 3D T1-weighted sequences, (iii) WM microstructural abnormalities at tract-based spatial statistics on diffusion-tensor imaging. The spatial association between maps and expression of 313 genes according to the Allen Human Brain Atlas was obtained with the MENGA platform. Functional-enrichment analysis investigated the overrepresented biological processes involving the genes significantly associated with the different types of brain damage. <h3>Results:</h3> T2-hyperintense lesions were mainly located in the periventricular WM; GM atrophy was observed in the visual, prefrontal cortex, and insula, WM atrophy selectively involved the optic tracts; patients also had a widespread increase of WM mean diffusivity and no fractional anisotropy abnormalities. The expression of AQP4 and C5 were associated with all types of brain damage, IL6 family signal transducer was associated with brain atrophy only, and CD59 was protective. Interferon-gamma, interleukin-4/-13 signalling and activation of C3/C5 were associated with both lesions and microstructural abnormalities. Pathways sometimes not specific for NMOSD pathogenesis were associated with brain atrophy. <h3>Conclusions:</h3> Brain lesions and WM microstructural abnormalities are associated with biological processes specific of AQP4+NMOSD, including complement activation and eosinophils/neutrophils recruitment. More complex mechanisms contribute to atrophy. <b>Disclosure:</b> Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA. Loredana Storelli has nothing to disclose. Elisabetta Pagani has nothing to disclose. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck . Dr. Moiola has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Genetic Variants in Iron Metabolism impact Disease Progression in MS through HIF1A (S9.006)

Genetic Variants in Iron Metabolism impact Disease Progression in MS through HIF1A (S9.006)

Trofinetide for the treatment of Rett syndrome: an open-label study in girls 2 to 4 years of age (P13-9.005)

Trofinetide for the treatment of Rett syndrome: an open-label study in girls 2 to 4 years of age (P13-9.005)

Treatment with trofinetide shows benefit compared to placebo for the ability to communicate in individuals with Rett syndrome: a secondary analysis of the LAVENDER study (P13-9.006)

Treatment with trofinetide shows benefit compared to placebo for the ability to communicate in individuals with Rett syndrome: a secondary analysis of the LAVENDER study (P13-9.006)

Myelin Density in Normal-Appearing White Matter in Measurements by q-Space Diffusional MRI Correlates with Clinical Disability in Multiple Sclerosis (P10-3.005)

Myelin Density in Normal-Appearing White Matter in Measurements by q-Space Diffusional MRI Correlates with Clinical Disability in Multiple Sclerosis (P10-3.005)

A Phase 2 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX005 in Patients with, or at Risk of, Manifest Huntington’s Disease (HD) (S32.009)

A Phase 2 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX005 in Patients with, or at Risk of, Manifest Huntington’s Disease (HD) (S32.009)

Long-Term Treatment With First-Line Ocrelizumab in Patients With Early RMS: 9-Year OPERA Subgroup Analysis (S46.002)

Long-Term Treatment With First-Line Ocrelizumab in Patients With Early RMS: 9-Year OPERA Subgroup Analysis (S46.002)

A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (S49.008)

A Prospective Natural History Study of Patients with Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia (ALSP) (S49.008)

The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathies (S37.004)

The Synuclein-One Study: Skin Biopsy Detection of Phosphorylated alpha-synuclein for Diagnosis of the Synucleinopathies (S37.004)

Neuropathy as an adverse effect of proteasomal inhibitors in multiple myeloma treatment: a network meta-analysis (P11-8.004)

<h3>Objective:</h3> To determine the comparative risk of incidence of neuropathy associated with proteasomal inhibitors (PIs) in multiple myeloma (MM) patients. <h3>Background:</h3> PIs (bortezomib, carfilzomib, ixazomib) are commonly used in treating MM. Bortezomib is traditionally associated with peripheral neuropathy, but it remains unclear whether its adverse effects also mirror the class-specific neurotoxic profile of PIs. Newer oral proteasome inhibitor, ixazomib, has fewer incidences of neuropathy. However, a direct comparison of neuropathy as a side effect of individual PIs has not been performed. <h3>Design/Methods:</h3> Published randomized control trials (RCTs) reporting neuropathy in MM patients (newly diagnosed and/or relapsed) treated with PI were searched up to May 2021. Studies where PIs were used along with chemotherapy vs. placebo, or no additional drugs (control) in the other arm were included. The primary outcome was the presence of neuropathy after follow-up. Pair-wise meta-analysis and network meta-analysis were performed using the frequentist’s approach to estimate the odds ratio (OR). <h3>Results:</h3> Eleven randomized clinical trials with a total of 3576 MM patients were evaluated in the analysis, which reported the incidence of neuropathic events. A total of nine studies on bortezomib(6), ixazomib(2), and carfilzomib(1) reported neuropathic events against a control group. Two studies compared bortezomib to carfilzomib. There was a significant increase in all grade (OR = 2.51, 95% CI 1.54–4.09) and high-grade neuropathy (based on CTCAE criteria) (OR = 3.37, 95% CI 2.36–4.81) among patients treated with any PI compared to control. Among the PIs, bortezomib was associated with a maximum risk of all-grade neuropathy (OR 4.00; 95% CI 3.30–4.85). <h3>Conclusions:</h3> Our results showed that treatment with bortezomib is associated with the highest risk of neuropathy among PIs in MM patients. This may warrant increased awareness among treating physicians and close monitoring of patients treated with these agents. <b>Disclosure:</b> Dr. Garg has nothing to disclose. Avash Das has nothing to disclose. Mr. GUPTA has nothing to disclose. Prof. KUMAR has nothing to disclose. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda Pharmaceuticals. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Roy has stock in Cabaletta bio. . The institution of Dr. Roy has received research support from Martin Shubik Fund for IBM at Yale University.

Frequency of anti-IgLON5 disease in patients who meet the clinical diagnostic criteria for progressive supranuclear palsy/corticobasal syndrome (S22.010)

<h3>Objective:</h3> To confirm the prevalence of anti-immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease in patients who fulfill the diagnostic criteria for progressive supranuclear palsy (PSP) or corticobasal syndrome (CBS). <h3>Background:</h3> Anti-IgLON5 disease can present symptoms that mimic PSP and CBS, including vertical supranuclear gaze palsy and parkinsonism. Some patients who are diagnosed with PSP or CBS are expected to have anti-IgLON5 antibodies; however, the frequency of such patients remains unknown. <h3>Design/Methods:</h3> We included 360 subjects enrolled in the Japanese Longitudinal Biomarker Study in PSP and Corticobasal Degeneration (JALPAC). We noted the age and sex of each patient and evaluated their diagnosis using diagnostic criteria for each subtype of PSP (PSP with Richardson’s syndrome [PSP-RS], PSP with parkinsonism [PSP-P], PSP-pure akinesia with gait freezing [PSP-PAGF], and PSP with cerebellar ataxia [PSP-C]), and using the revised Cambridge criteria and Armstrong criteria for CBS. In patients who fulfilled any diagnostic criteria, we then tested serum anti-IgLON5 antibodies via a cell-based assay. <h3>Results:</h3> Of 360 subjects in JALPAC, 223 fulfilled at least one of the diagnostic criteria for possible or probable PSP/CBS. The median age of these 223 patients was 73 (range 51–88) years; 123 (55%) were male. The numbers of patients who met each set of criteria were as follows: PSP-RS, 52; PSP-PAGF, 6; PSP-C, 2; CBS, 117; PSP-RS and CBS, 37; PSP-PAGF and CBS, 4; PSP-RS and PSP-PAGF, 1; PSP-RS and PSP-P, 1; PSP-P and CBS, 1; PSP-RS, PSP-PAGF, and CBS, 1; and PSP-RS, PSP-C, and CBS, 1. All 223 patients were negative for anti-IgLON5 antibodies. <h3>Conclusions:</h3> Anti-IgLON5 disease is likely absent or extremely rare in patients who meet the diagnostic criteria for PSP/CBS and have typical clinical presentations. Atypical symptoms such as sleep disturbance, dysautonomia, and respiratory failure may be crucial clinical features of anti-IgLON5 disease with PSP-/CBS-like presentations. <b>Disclosure:</b> Yoya Ono has nothing to disclose. Akira Takekoshi has nothing to disclose. Dr. Yoshikura has nothing to disclose. Dr. Takigawa has nothing to disclose. Ikuko Aiba has nothing to disclose. Ritsuko Hanajima has nothing to disclose. Dr. Kowa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for DAIICHI SANKYO COMPANY, LIMITED. Dr. Kowa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eli Lilly Japan K.K.. Dr. Kowa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka Pharmaceutical Co., Ltd.. Dr. Kowa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen Inc.. Dr. Kowa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharmaceutical Company Limited.. Dr. Kowa has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Kyowa Kirin Co., Ltd.. Dr. Kowa has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Chugai Pharmaceutical Co., Ltd.. Dr. Kowa has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for ONO PHARMACEUTICAL CO., LTD.. Dr. Kanazawa has nothing to disclose. Dr. ?? has nothing to disclose. Aya Tokumaru has nothing to disclose. Dr. Morita has nothing to disclose. Dr. Hasegawa has nothing to disclose. Kenji Nakashima has nothing to disclose. Dr. Ikeuchi has nothing to disclose. Dr. Kimura has nothing to disclose. Dr. Shimohata has nothing to disclose.

Correlation of 18F-PM-PBB3 (18F-florzolotau) Tau PET Imaging with Postmortem Neuropathological Findings in A Case with Progressive Supranuclear Palsy (P9-11.015)

<h3>Objective:</h3> To examine correlations between <i>in vivo</i> positron emission tomography (PET) imaging with 18F-PM-PBB3 (18F-florzolotau) and postmortem neuropathological findings in a patient with progressive supranuclear palsy (PSP). <h3>Background:</h3> There have been no reports demonstrating tight PET-pathology associations in the same individual with non-Alzheimer-type neurodegenerative disorders, including PSP, characterized by aggregations of four-repeat tau isoforms only. 18F-florzolotau is a PET probe allowing high-contrast imaging of Alzheimer’s and non-Alzheimer tau pathologies irrespective of isoform compositions, while the utility of this tracer for quantifying the abundance of tau deposits in living cases is yet to be verified. <h3>Design/Methods:</h3> <h3>Patient:</h3> A 65-year-old male with a clinical diagnosis of PSP Richardson syndrome underwent 11C-PiB amyloid and 18F-florzolotau tau PET scans one year before autopsy. Clinical, neuroimaging, and neuropathological findings in this case were briefly summarized elsewhere (K Tagai, et al. Neuron 2021). <h3>Image analysis:</h3> The standardized uptake value ratio (SUVR) image was generated from averaged PET images at 90–110 min after injecting 18F-florzolotau. The reference region was determined using an optimized reference tissue method (K Tagai, et al. medRxiv DOI: https://doi.org/10.1101/2022.02.13.22270135). <h3>Neuropathological analysis:</h3> Quantitative analysis of tau burden was performed using an anti-phosphorylated tau antibody (AT8). A threshold-based binarization method was used for determining the mean AT-8-positive area (%area tau burden). <h3>Results:</h3> 18F-florzolotau PET showed enhanced radiosignals in the brainstem, subthalamic nucleus, and basal ganglia, and the presence of PSP-characteristic tau deposits, including the globose neurofibrillary tangle, tufted astrocytes and coiled bodies, primarily in these areas was confirmed by neuropathological assays. There was a close correlation between regional radioprobe SUVR and %area tau burden (<i>r</i><i>_s</i> = 0.63, <i>p</i> &lt;0.0001). Amyloid PET was negative by visual read. <h3>Conclusions:</h3> 18F-florzolotau PET measures reflect the abundance of tau pathologies in PSP. <b>Disclosure:</b> Dr. Endo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for APRINOIA Therapeutics. Dr. Endo has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AbbVie Inc.. The institution of Dr. Endo has received research support from JSPS KAKENHI 21K15705. Dr. Araki has nothing to disclose. Dr. Takeda has nothing to disclose. Dr. Takado has nothing to disclose. Dr. Tagai has nothing to disclose. Dr. Matsuoka has nothing to disclose. Dr. Seki has nothing to disclose. Dr. Takahata has nothing to disclose. Dr. Sahara has nothing to disclose. Hitoshi Shinotoh has nothing to disclose. Mr. Kawamura has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Honda has nothing to disclose. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eli lilly. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharmaceutical . Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Nihon Medi-Physics. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for FUJIFILM Toyama Chemical. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunplanet . Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for NIPPON CHEMIPHAR. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sumitomo Pharma. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GE Healthcare. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for CHUGAI PHARMACEUTICAL. Prof. SHIMADA has received intellectual property interests from a discovery or technology relating to health care. Prof. SHIMADA has received publishing royalties from a publication relating to health care. Prof. SHIMADA has received publishing royalties from a publication relating to health care. Prof. SHIMADA has received publishing royalties from a publication relating to health care. The institution of Dr. Higuchi has received research support from APRINOIA Therapeutics.

Feasibility Assessment of Facilitated Subcutaneous Immunoglobulin 1.0 G/Kg with Abbreviated Dose Ramp-Up and without Ramp-Up: A Phase 1 Tolerability and Safety Study in Healthy Adults (P6-4.003)

<h3>Objective:</h3> To assess the feasibility of infusions of facilitated subcutaneous immunoglobulin (fSCIG; immunoglobulin infusion with recombinant human hyaluronidase) at a 1.0g/kg target dose via an abbreviated dose ramp-up or no ramp-up versus conventional ramp-up in healthy participants, based on tolerability and safety outcomes. <h3>Background:</h3> When transitioning from intravenous to facilitated subcutaneous dosing, dose ramp-up is used to incrementally increase infusion volumes to achieve target doses, acclimating patients to high-volume infusions. <h3>Design/Methods:</h3> This phase 1, open-label, single-center trial enrolled healthy adults aged 19–50 years (NCT04578535). Participants were assigned into three fSCIG arms (each with a 1.0g/kg target dose): (1) conventional dose ramp-up (0.25g/kg [Week 1] to 1.0g/kg [Week 8]), (2) abbreviated dose ramp-up (0.50g/kg [Week 1] to 1.0g/kg [Week 5]), or (3) 1.0g/kg without ramp-up. fSCIG tolerability (primary endpoint) was assessed as the proportion of participants completing all initiated infusions without interruptions or infusion rate reduction owing to treatment-emergent adverse events (TEAEs). Safety endpoints included the rates of TEAEs per person-year. <h3>Results:</h3> Overall, 27 participants were enrolled (mean age 34.9 years); with 8, 9, and 10 participants in the conventional, abbreviated, and no ramp-up arms, respectively. Participants completed all initiated infusions. No discontinuations due to TEAEs occurred but discontinuations were proportionally highest in the no ramp-up group. In total, 69.7, 74.0 and 99.7 TEAEs occurred per person-year in the conventional, abbreviated and no ramp-up arms, respectively. No serious or severe TEAEs occurred. <h3>Conclusions:</h3> fSCIG was well-tolerated in healthy adults with or without dose ramp-up at a 1.0 g/kg target dose, but the higher proportion of discontinuations in the no ramp-up arm may provide indirect evidence of better tolerability with ramp-up. The feasibility of abbreviated ramp-up was demonstrated by the lower TEAE rates seen in the dose ramp-up arms. Therefore, administration schedules can be individualized according to physician discretion based on tolerability. <b>Disclosure:</b> Zhaoyang Li has received personal compensation for serving as an employee of Takeda. Andras Nagy has nothing to disclose. Mr. Khaskhely has nothing to disclose. Mr. Lindner has received personal compensation for serving as an employee of Takeda. Mr. Lindner has stock in Takeda. Kimberly Duff has nothing to disclose. Dr. Garcia has received personal compensation for serving as an employee of Takeda Pharmaceutical Company Limited. Dr. Garcia has stock in Takeda Pharmaceutical Company Limited. Dr. AY has received personal compensation for serving as an employee of Takeda. Dr. Rondon has nothing to disclose. Prof. Yel has received personal compensation for serving as an employee of Takeda. Prof. Yel has stock in Takeda. Prof. Yel has received publishing royalties from a publication relating to health care.

Patient Concept Elicitation Interviews: Insights into Multiple System Atrophy (MSA) Patient Experiences and Relevance of a modified United Multiple System Atrophy Rating Scale (P8-9.003)

Patient Concept Elicitation Interviews: Insights into Multiple System Atrophy (MSA) Patient Experiences and Relevance of a modified United Multiple System Atrophy Rating Scale (P8-9.003)

Real World Experience of New MG Therapies: Single Center Cohort Study (P7-8.012)

Real World Experience of New MG Therapies: Single Center Cohort Study (P7-8.012)

The Impact of Generalized Myasthenia Gravis Severity on Work and Daily Activities: A Real World Study (P7-8.006)

<h3>Objective:</h3> To explore the relationship between generalised myasthenia gravis (gMG) severity and the ability to work and perform normal daily activities. <h3>Background:</h3> GMG is a rare and chronic autoantibody neuromuscular disease which manifests as muscle weakness and fatigue. The symptoms of gMG may affect patients’ ability to work and perform daily activities. <h3>Design/Methods:</h3> Data came from the Adelphi gMG Disease Specific Programme (DSP), a cross-sectional survey of MG treating physicians and their consulting MG patients, administered in 5 European countries and the US between March and September 2020. Patient data included demographics, severity based on Myasthenia Gravis Foundation of America (MGFA) classification (class I least severe, class V most severe) and the Charlson Comorbidity Index (CCI). Patients completed the Work, Productivity and Activity Impairment (WPAI) questionnaire. Linear regressions assessed the relationship between MGFA class and WPAI while controlling for age and CCI. <h3>Results:</h3> A total of 257 people with MGFA class II-IV (gMG) completed at least one of the WPAI questions: 40% were employed full/part-time, 41% were on long-term sick leave or retired. Mean age was 54.7 years; 52.9% were male. There was no significant association between MGFA class II or III-IV on the percentage of work time missed (n=90, <i>p</i>=0.44). MGFA class III-IV gMG were associated with a 14.3% higher impairment while working vs class II (n=94, <i>p</i>=0.01) and were associated with 14.8% higher overall work impairment due to gMG (n=84; <i>p</i>=0.04). Respondents with class III-IV gMG reported 15.5% higher impairment in normal daily activities than the less severe class II respondents (n=257, <i>p</i>&lt;0.01). <h3>Conclusions:</h3> Generalized Myasthenia Gravis impacts the ability to work and perform daily activities with more severe disease associated with greater impairment. Treatments that control symptoms resulting in less severe disease could have a positive impact on work and daily activities of patients living with gMG. <b>Disclosure:</b> Dr. Pesa has received personal compensation for serving as an employee of Janssen. Dr. Pesa has stock in J&amp;J. Dr. Chaudhry has received personal compensation for serving as an employee of Johnson &amp; Johnson. Dr. Chaudhry has received personal compensation for serving as an employee of Takeda Pharmaceuticals. Jonathan de Courcy has nothing to disclose. Miss Barlow has nothing to disclose. Miss Chatterton has nothing to disclose. Mr. Thomas has nothing to disclose. Mr. Gibson has nothing to disclose. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MT pharma. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catalyst. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche . Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. Dr. Govindarajan has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Alexion. Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for MT pharma . Dr. Govindarajan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Catalyst. The institution of Dr. Govindarajan has received research support from Band of Hope . The institution of Dr. Govindarajan has received research support from Alexion. Dr. Govindarajan has received publishing royalties from a publication relating to health care.

Mills’ Disease Variant (P3-8.012)

Mills’ Disease Variant (P3-8.012)

Early B cell tolerance defects in anti-neurofascin 155 mediated chronic inflammatory demyelinating polyneuropathy (S40.005)

Early B cell tolerance defects in anti-neurofascin 155 mediated chronic inflammatory demyelinating polyneuropathy (S40.005)

Toward a Biomarker Panel measured in CNS-originating Extracellular Vesicles for Differential Diagnosis of Parkinson’s Disease and Multiple System Atrophy (S37.005)

Toward a Biomarker Panel measured in CNS-originating Extracellular Vesicles for Differential Diagnosis of Parkinson’s Disease and Multiple System Atrophy (S37.005)

Clinical Implications of Specific Autoantibodies in Chronic Inflammatory Neuropathies (P11-8.013)

<h3>Objective:</h3> A large-scale, in-depth analysis of clinical, electrophysiological characteristics and treatment response of autoantibody associated immune-mediated neuropathies. <h3>Background:</h3> Chronic inflammatory neuropathies (CINs) can have varied clinical presentations. In the past two decades several autoantibodies have been identified in CIN patients. While the literature suggests specific clinical phenotypes with some of these autoantibodies, the full range of possible presentations and the associated clinical syndromes of each antibody requires additional investigation. <h3>Design/Methods:</h3> We reviewed the electronic medical records of adult patients undergoing evaluation for immune mediated neuropathies between 01/01/2012 and 04/01/2022 at our institution who were assessed for autoantibodies. The clinical presentations, laboratory work-up, electrodiagnostic studies, and treatment responses were reviewed for this ongoing project. <h3>Results:</h3> This analysis resulted in a total of 1168 patients who were evaluated for CIN-associated autoantibodies. Anti-trisulfated-heparin-disaccharide (TS-HDS) autoantibodies were present in 266 (22.8%) patients, anti-fibroblast-growth-factor-receptor-3 (FGFR3) autoantibodies were present in 200 (17.1%) patients and 33 (2.8%) patients were positive for anti-neurofascin (NF)-140/155 autoantibodies. Other autoantibodies were rare (&lt;1%), and multiple autoantibodies were detected in some patients.. Interestingly, some patients with anti-NF presented with focal sensorimotor dysfunction prior to subsequent bilateral involvement. About 20% of patients with anti-NF autoantibodies had predominant demyelinating features in electrodiagnostic studies. Anti-FGFR3 autoantibodies were often associated with sensory involvement, but sometimes motor dysfunction was also present. Anti-TS-HDS-associated CIN had a more varied clinical presentation. There were differences in therapeutic response based on the associated autoantibodies; however, the therapeutic decision was provider-specific, and a direct comparison was not feasible. <h3>Conclusions:</h3> Autoantibodies associated with CINs can have a variety of often overlapping motor and sensory presentations. In a subset of patients, their presence can help gauge therapeutic responsiveness. However, in some cases, they may represent an epiphenomenon, and further studies are warranted. <b>Disclosure:</b> Dr. Bushlyar has nothing to disclose. Dr. Zubair has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for The MedNet. Dr. Cardenas Castillo has nothing to disclose. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genentech. Kevin O’Connor has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Viela Bio. Kevin O’Connor has received stock or an ownership interest from Cabaletta. Dr. DiCapua has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. DiCapua has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Argenx. Dr. Desai has nothing to disclose. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Momenta . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Immunovant . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio . Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Viela Bio. Dr. Nowak has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cour Pharma. The institution of Dr. Nowak has received research support from Ra Pharma. The institution of Dr. Nowak has received research support from Alexion . The institution of Dr. Nowak has received research support from Momenta . The institution of Dr. Nowak has received research support from Immunovant . Dr. Nowak has received research support from argenx. Dr. Nowak has received research support from Viela Bio . Dr. Nowak has a non-compensated relationship as a Member of the Board of Directors with Myasthenia Gravis Foundation of America (MGFA) that is relevant to AAN interests or activities. Dr. Tseng has nothing to disclose. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda Pharmaceuticals. Dr. Roy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for argenx. Dr. Roy has stock in Cabaletta bio. . The institution of Dr. Roy has received research support from Martin Shubik Fund for IBM at Yale University.