GBS-CIDP Foundation Research Grant Program (Elevation Awards)

GBS-CIDP Foundation Research Grant Program (Elevation Awards) is sponsored by GBS-CIDP Foundation International. This award funds smaller projects or portions of projects related to GBS, CIDP, and variants. Availability should be confirmed by emailing the foundation.

Foundation Funded Research - GBS | CIDP Foundation International Foundation Funded Research To date, the GBS|CIDP Foundation has awarded more than $8 million in grants meant to advance the knowledge of GBS, CIDP, and variants. Read on to learn about the projects that were chosen based on recommendations from the Grant Committee of the Global Medical Advisory Board. All grants awarded before 2021 were awarded in amounts of up to $60,000.

Foundation Funded Research Update Access This Speaker Series Summary Here Dr. med. Martin K. R.

Svačina, UTHealth Science Center Houston Study: Effects of Efgartigimod on Endoneurial Inflammation in Preclinical Models of Immune Neuropathies Dr. Saraswati Nashi, National Institute of Mental Health and Neuro Sciences, Bangalore, India, Study: Exploring the genetic risk factors underlying differential responses to treatment in Inflammatory Neuropathies in an Indian Cohort 2024 Discover Grant Awardees Chiara Briani MD, University of Padova Study : Non-invasive monitoring of MYD88L265P in patients with anti-MAG antibody neuropathy treated with zanubrutinib (bioMAZINGA) Daniela Latorre, PhD, Institute of Microbiology, ETH Zurich, Switzerland Study : Dissecting autoreactive T cell immunity in distinct Guillain-Barré syndrome variants Ruth Huizinga, MD, Erasmus MC, University Medical, Center, Rotterdam Study: Biomarkers for paranodal injury in Guillain-Barré syndrome 2023 Discovery Grant Awardees Title: Evaluating Janus Kinase (JAK) Inhibition for Treatment of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Maureen A.

Su, MD, UCLA Synopsis: Despite optimization of existing treatment regimens, advancements in Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) treatment have not kept pace with our improved understanding of disease pathogenesis.

Recent studies by our lab and others have demonstrated the dysregulation of multiple inflammatory cytokines in CIDP, suggesting interventions which broadly inhibit cytokine signaling may be necessary to inhibit pathogenesis1-5. In our mouse model of CIDP, we have shown that interleukin-10 (IL-10), interferon-γ (IFN-γ), and IL-21 signaling promote disease development.

Janus kinase (JAK)-mediated STAT phosphorylation is involved in signaling by various cytokines, including IL-10, IFN-γ, and IL-21. Therefore, disruption of this pathway using existing, FDA approved JAK inhibitors is an attractive treatment strategy for CIDP6. These inhibitors are currently used to treat multiple autoimmune conditions with ongoing clinical trials likely to broaden their use.

Given the role of the JAK-STAT signaling pathway in CIDP, we hypothesize that JAK inhibition will confer protection against peripheral nerve autoimmunity through interruption of multiple cytokine signaling pathways. We plan to perform functional assays to characterize the effect of JAK inhibition on immune cell pathogenicity in vitro and in vivo.

Title: Neurofilament light chain as biomarker to define the disease dynamics, subtype and prognosis of the Guillain-Barré syndrome: Bart C. Jacobs1, Thomas Harbo2, Zhahirul Islam3, Mike Lunn4, Luis Querol5, for the IGOS Consortium, Erasmus University Medical Centre, Rotterdam, Synopsis: Neurofilament light chain (NfL) is a specific marker for axonal injury.

Previous studies indicated that serum NfL levels are increased in Guillain-Barré syndrome (GBS), especially in patients with severe and axonal forms with poor outcome. NfL is a potential biomarker to monitor axonal injury and predict prognosis in GBS but further studies are required.

The aim of the current study to use the cohort of the prospective International GBS Outcome Study (IGOS) and ultrasensitive SIMOA technology (1) to determine the serum NfL levels in relation to preceding infections, anti-ganglioside antibodies and clinical course, (2) improve the subtype classification which is currently based on nerve conduction studies only, (3) improve the current prognostic models to predict the clinical outcome in individual patients and (4) to better understand the role of axonal damage in long-term disability and complaints.

These NfL test results will also increase the impact of all future biobank studies conducted by the IGOS Consortium.

Title: Involvement of microRNA-155 dysregulation in T Helper 17 cell differentiation in the pathogenesis of Guillain–Barre syndrome: Israt Jahan (PhD fellow), Division, icddr,b, Bangladesh; Department of Medical Microbiology and Infectious Diseases, Erasmus University Synopsis: Guillain–Barre syndrome (GBS), an immune-mediated disorder, mostly preceded by Campylobacter jejuni, with 14% mortality in Bangladesh.

Despite of effective treatments such as plasma exchange or intravenous immunoglobulin (IVIg), only 10% patients receive specific treatments due to high expense and one-third of them do not respond to the treatment in Bangladesh. Etiology of GBS still needs to be understand in terms of involvement of genetic factors and there role in immune regulation.

Growing evidence suggested, microRNAs (miRNAs) involve in regulating the immune response in autoimmune diseases. Therefore, we hypothesized that dysregulation in miR-155 expression regulates the Th17 cell differentiation that involve in the pathogenesis and treatment response in GBS. we designed a case-control study with patients with GBS and age-matched controls (C.

jejuni enteritis and healthy controls). We will (I) determine miR-155 expression and Th17 cells differentiation and find association with GBS disease activity, severity and treatment response; and II) function of miR-155 in Th17 cell differentiation. CD4+ T cells of acute phase, 4 and 26 weeks will be used to extract total RNA and measure miR-155, STAT3 and RORƴt mRNA expression and Th17 cell differentiation.

Function of miR-155 will be evaluated with miR-155 transfection study. From this study, we will find new insight to understand the function of miR-155 in Th17 cell regulation to monitor GBS disease activity and treatment response. Title Deciphering autoreactive T cell immunity in patients with COVID-19-associated Guillain-Barré syndrome.

Daniela Latorre, PhD, Institute of Microbiology, ETH Zurich Synopsis: Guillain-Barré syndrome (GBS) is an immune-mediated disorder of the peripheral nervous system (PNS) usually triggered by a preceding bacterial or viral infection 1. An association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and new-onset of a large spectrum of neurological manifestation, including GBS, has been recently shown 2, 3.

However, the underpinning pathophysiological mechanisms remain elusive 2. Current observations exclude a direct humoral- or viral-mediated pathology in COVID-19-associated GBS, thus suggesting that additional immune-mediated processes may be involved 2, 4, 5.

Based on our recent data demonstrating the existence of self-reactive T cells in patients with GBS not associated to COVID-19 (manuscript in preparation), the proposed project aims at investigating autoreactive T cell immunity in COVID-19-associated GBS.

To this end, the project includes 3 main Aims: Aim 1 is to explore frequency distribution of immune cell subsets ex vivo in the blood by flow cytometry; Aim 2 is to characterize antigen specificity, T cell receptor repertoire and phenotype of PNS-myelin- as well as SARS-CoV-2-specific T cells in the cerebrospinal fluid (CSF) and blood from GBS patients by in vitro screenings 6; Aim 3 is to examine T cell cross-reactivity between self- and SARS-CoV-2-antigens by sequential in vitro antigenic stimulation 7.

The outcomes of this project may have substantial impact in understanding T cell immunity in COVID-19-associated GBS and, potentially, in a larger spectrum of COVID-19-associated neurological disorders, thus shedding light into a controversial and relevant medical challenge.

IgM and IgG GM1 antibodies in MMN versus GBS/AMAN inflammatory neuropathies Dr. Nicolas Dubuisson, Nuffield Department of Clinical Neurosciences Synopsis: The aim of the project is to define and compare the B cell immunology underlying the acute and chronic inflammatory neuropathies, associated with IgG and IgM class antibodies, respectively.

The inflammatory neuropathies are devasting disorders in which immune-mediated damage to peripheral nerves leads to progressive disability. The clinically defined syndromes are undoubtedly pathologically heterogenous, and current treatments are poorly targeted and incompletely effective.

We propose that the inflammatory neuropathies can be categorised into three groups based on the presence (or absence) of peripheral nerve reactive IgG1, IgG4 or IgM autoantibodies. We hypothesise that distinct immunopathological processes underly each of the serologically defined conditions, and that these explain the group differences in disease course, relapse rates and response to treatment.

The proposed research will identify and characterise the B cells responsible for generating the different classes of GM1 autoantibodies associated with acute motor axonal neuropathy (AMAN, IgG1/3) and multifocal motor neuropathy (MMN, IgM) respectively. These will be exploited to generate disease-relevant, human, monoclonal antibodies.

We will determine the factors which promote and maintain autoantibody production in bulk cultures, and use singly-sorted B cells to identify defects in self-tolerance. We will define the immunological autoantigen-specific lineage, and map the evolution of high affinity, pathogenic antibodies by tracking B-cell receptor mutations through the developing autoimmune response.

At each stage monoclonal antibodies will be generated, and their epitopes, affinities and pathogenic potential carefully evaluated. This will increase understanding of both the induction and effector phases of these diseases and should ultimately inform the use of more tailored and effective therapies.

In addition, the facilities and equipment required for the project are all available within the department’s main base at the John Radcliffe Hospital. The hospital also hosts one of the largest clinical neurology departments in the United Kingdom with particular expertise in neuromuscular disorders.

2022 Discovery Grant Awardees Principal Investigator: Dr. Pietro Emiliano Doneddu, MD Humanitas Clinical and Research Hospital-IRCCS, Italy Title of Project : Dissecting the genetic architecture of chronic inflammatory demyelinating Synopsis: In this study, we aim to characterize the genetic architecture of a large cohort of CIDP patients and healthy controls to evaluate whether specific alleles/haplotypes are implicated in the risk of CIDP, in its clinical and immunological variability, Principal Investigators: Dr. H.

G. (Ruth) Huizinga and Prof. Bart C. Jacobs Erasmus MC, University Medical Center Rotterdam, The Netherlands Title of Project : Pathogenicity of human antibodies cloned from Guillain-Barré syndrome patient Synopsis: This project aims to determine the pathogenic potential of human anti-GM1 antibodies.

More specifically, we will investigate whether human anti-GM1 antibodies: 1) have different fine specificities and affinities; 2) can induce axonal damage, demyelination or both.

Principal Investigators: PD Dr. Moritz Kronlage, MD University of Heidelberg, Germany Title of Project : MR-neurography in chronic inflammatory demyelinating polyradiculopathy (CIDP) Synopsis: To evaluate the diagnostic accuracy and utility of quantitative magnetic resonance neurography (MRN) for the longitudinal assessment of nerve integrity and therapy response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Principal Investigators: Dr. Ioannis Petropoulos Weill Cornell Medicine Qatar- Qatar Foundation, Qatar, Title of Project : Corneal Confocal Microscopy: An Objective Imaging Marker for Immune Activation and Neurodegeneration in Guillain Barre Syndrome Synopsis: To assess the relationship between corneal nerve loss and immune activation with the evolution of clinical disability and outcomes in different subtypes (AIDP, AMAN, MFS, post vaccine) of GBS.

Principal Investigators: Dr Eileen Mc Manus MB BCh BAO BA, MSc.

, Waikato Hospital, New Zealand Title of Project : The Guillain-Barre Syndrome (GBS) Phenotype in Aotearoa/New Zealand: How Ethnicity, Socioeconomics, and Infection Influence GBS Outcomes Synopsis: Guillain-Barre syndrome (GBS) is the commonest cause of acute paralysis worldwide GBS phenotypes are defined based on clinical, electrophysiological, and pathological characteristics [2].

NZ has the highest incidence of GBS in the world and the highest Campylobacteriosis infection rate in the developed world [3,4]. The excess of GBS is entirely attributable to Campylobacteriosis.

Diarrhoea as an antecedent event is strongly linked to more severe GBS [5] and to the acute motor axonal neuropathy (AMAN) phenotype [6] so it would be expected that there would be a higher rate of severe disease and of AMAN in NZ compared to other developed countries. Clinical experience suggests that Māori have a higher incidence of AMAN, the pharyngo-cervico-brachial (PCB) variant and Miller Fisher syndrome (MFS).

Māori also have a worse prognosis. We aim to develop a national registry for GBS in NZ. Currently, there is no GBS registry in NZ.

Principal Investigators: Jean-Philippe Camdessanché PhD, MD, University Hospital of Saint-Étienne, France Title of Project : Revealing the autoantigen repertoire of IVIg responders versus nonresponders with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Synopsis: About 20% of patients with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) do not respond to intravenous immunoglobulins (IVIg).

The reason is unknown and predicting markers are lacking. Our recent deep screening found IVIg responders targeting 3 times more antigens than non-responders in a cohort of 22 CIDP patients. Our primary objective is to validate this finding with an independent cohort.

Our secondary objective is to systemically analyze the targeted antigen repertoire to fident cohort. Our secondary objective is to systemically analyze the targeted antigen repertoire to find prognostic markers.

Study: Examining the Role of Microbiota in Inflammatory Peripheral Neuropathies Award Grantee: Gang Zhang, PhD, University of Texas, Health Sciences Center at Houston Autoimmune peripheral neuropathies are associated with dysregulated immune responses. The gut microbiome, the bacteria residing in gastrointestinal tract, plays a fundamental role in regulating the host immune system.

This proposal will help understand the role of microbiota in pathogenesis of inflammatory demyelinating neuropathies. Study: Influence of the small chain fatty acid propionic acid on the peripheral immune regulation in the context of chronic in­flammatory demyelinating polyneuropathy (CIDP) Award Grantee: Anna Lena Fisse, MD, Ruhr University Bochum St.

Josef Hospital, Germany The intestinal immune system and the community of intestinal microbes, the microbiome,determine autoimmune inflammation. Nutrition is a major influence factor on microbiome and supplementation of the fatty acid propionic acid showed positive immunomodulatory effects in diseases like multiple sclerosis.

The aim of this project is to investigate the immunomodulatory effect of propionic acid in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), who take propionic acid orally for 90 day.

Inhibition of the terminal complement pathway in EAN with a novel monoclonal antibody targeting C6; Frank Baas, MD, PhD, Prof, Leiden University Medical Center Leiden, The Netherlands In this project, we will show whether blockade of C6 is an attractive target, as generation of MAC is prevented, but in contrast to C5-inhibition, the C5a-induced pathways remain unaffected.

Nerve Ultrasound for Diagnosis and Prognosis of GBS ; Natalia Gonzalez, MD, and Lisa Hobson-Webb, MD, Duke University Medical Center Delay in Guillain-Barré syndrome (GBS) diagnosis and treatment is associated with higherfrequency of intubation and residual weakness.

We have two main objectives for this pilot study: (1) to define peripheral nerve ultrasound (US) measures diagnostic of GBS in the acutesetting and (2) to identify peripheral nerve US biomarkers of GBS prognosis.

Precision medicine in chronic inflammatory neuropathy assessment , Luis Querol MD PhD, Hospital de la Santa Creu i Sant Pau The aim of this project is to find precise tools that help optimize patientmonitoring in daily clinical practice by using two objective measures of disease activity: a wearablesystem to monitor gait parameters, and serum neurofilament levels, a novel blood biomarker of neuronal damage used in other neurological diseases.

If successful, this project will provide better tools to assess disease status and treatment effect and, ultimately, more precision in neurological assessment that help improve patient care and clinical trial outcomes.

Validation of novel biomarkers in acquired inflammatory neuropathies; Professor Michael Lunn, Institute of Neurology, University College London (UCL) Inflammatory neuropathies are a heterogeneous group of acquired nerve-damaging disorders, which commonly have life-changing implications for sufferers. The most common chronic immune-mediated form, CIDP, has an estimated prevalence of 3 per 100,000 in the United Kingdom1.

To resolve these unmet needs, we will identify novel POEMS, GBS and CIDP biomarkers Lenalidomide in anti-MAG Neuropathy: Phase 1b Study ; : Amro Stino, MD, University of Michigan Medical School We aim to assess the safety profile and maximum tolerated dose of Lenalidomide in anti-MAG neuropathy. Drug efficacy will serve as secondary outcome.

Lenalidomide is current standard of care therapy in the treatment of paraproteinemic neuropathies, namely osteosclerotic myeloma (POEMS syndrome), amyloid, and multiple myeloma. Its safety and efficacy in anti-MAG IgM associated demyelinating neuropathy (DADS syndrome) has not been previously explored.

Research Grant Update 2023 Optimizing (electro) diagnosis in CIDP with machine learning ; Camiel Verhamme MD PhD, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands Despite current diagnostic criteria sets for CIDP, the rate of misdiagnosis is high. In this project, our aim is to develop machine learning (ML) algorithms with improved (electro) diagnostic accuracy for CIDP as compared to current criteria sets.

Proteomics based discovery of disease activity biomarkers in chronic inflammatory demyelinating polyneuropathy , Luuk Wieske MD PhD, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands Patients suffering from and clinicians treating chronic inflammatory demyelinating polyneuropathy (CIDP) are currently lacking disease activity biomarkers that can provide objective guidance on when to start and stop treatment.

Serum proteins may serve as quantitative, responsive and easily obtainable disease activity biomarkers.

In this project, our aim is to identify potential disease activity biomarkers by screening a focused blood proteome comprised of 184 proteins related to the nervous system and inflammation Research Grant Update – 2023 Pathogenic Th17 cell pathology in CIDP : Karissa Gable, Duke University Evidence from our lab, supported by the medical literature, suggests that T helper cells producing IL-17 (Th17) are important mediators of inflammation in CIDP.

We propose to deeply characterize pathogenic Th17 cell populations in CIDP and determine the effects of Th17 targeted therapy for this disease. Treatments for CIDP have not advanced significantly in many years and new treatment approaches are needed.

Recent Study Update – June 2021 A randomized controlled trial with Rituximab versus placebo in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDPRIT): support for an additional dose of Rituximab after six months of therapy; EDUARDO NOBILE-ORAZIO, Milan University, IRCCS Humanitas In this study, immunoglobulin therapy will be continued for six month after initial rituximab therapy to allow rituximab to become effective.

We originally proposed the same protocol shown to be effective in another immunological disease (rheumatoid arthritis) with rituximab at the dose of 1000 mg intravenously versus placebo on day 1 and 15 after randomization.

After reconsidering the results of the rituximab trial in arthritis rheumatoid where its efficacy was significant after 24 weeks but declined at week 48, with proposed an amendment to our Ministry of Health to add a further 1 g dose of rituximab or placebo 6 months after the initial therapy, one week after IVIg suspension (see attached revised protocol).

This decision took into account the fact that the primary end-point of the study was the different proportion of patients relapsing within 12 months after therapy initiation. This amendment was approved without further financial support for the additional therapy. Development of New Biomarkers Using Immune Cells Profiling and T-cell Specific Sequencing ; A.

JUNG-JOON SUNG, Seoul National University College In this study, immunoglobulin therapy will be continued for six month after initial rituximab therapy to allow rituximab to become effective. We originally proposed the same protocol shown to be effective in another immunological disease (rheumatoid arthritis) with rituximab at the dose of 1000 mg intravenously versus placebo on day 1 and 15 after randomization.

After reconsidering the results of the rituximab trial in arthritis rheumatoid where its efficacy was significant after 24 weeks but declined at week 48, with proposed an amendment to our Ministry of Health to add a further 1 g dose of rituximab or placebo 6 months after the initial therapy, one week after IVIg suspension (see attached revised protocol).

This decision took into account the fact that the primary end-point of the study was the different proportion of patients relapsing within 12 months after therapy initiation. This amendment was approved without further financial support for the additional therapy.

Exploring possible role of TGR5 and FXR in autoimmune neuropathy ; BETTY SOLIVEN, University of Chicago There is increasing evidence that diet and gut microbiome regulate the immune function via changes in short chain fatty acids and other metabolites, but also via altering the bile acid composition in the host. These microbially generated secondary bile acids are signaling molecules that interact with multiple host bile acid receptors.

For this pilot study, we plan to focus on a G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5), and type 2 nuclear receptor called farnesoid X receptors (FXR), both of which are activated by bile acids and are implicated in the control of the immune system.

Both TGR5-selective agonist and FXR-selective agonist have been shown to modulate the function of monocytes and macrophages, but their effects on lymphocytes have not been as well-elucidated.

The goal of this pilot study is to investigate our hypothesis that altered expression or function of TGR5 or FXR could contribute to the pathogenesis or disease progression in Guillain Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).

Recent Study Update – June 2021 Neuromuscular ultrasound (NMUS) parameters as diagnostic and prognostic biomarker in chronic inflammatory demyelinating polyneuropathy (CIDP) ; H. G. (RUTH) HUIZINGA & BART C.

JACOBS, Erasmus MC, University Medical Center Antibodies (Abs) to gangliosides play a key role in the pathogenesis of a proportion of patients with Guillain-Barré syndrome (GBS). Although these Abs have been characterized extensively, little is known about the cells that produce these Abs.

We have recently demonstrated that plasmablasts, precursors of plasma cells, are elevated in the peripheral blood of one-third of the patients with GBS and that dominant B-cell clones can be identified. Moreover, preliminary data indicate that isolated plasmablasts can be cultured in vitro and secrete anti-ganglioside Abs. Further studies are required to substantiate these findings.

Recent Study Update – June 2021 Targeting Wallerian-like degeneration in GBS mouse models ; Elisabetta Babetto, Ph. D. , Research Assistant Professor; The Research Foundation for SUNY on behalf of U.

at Buffalo Axon degeneration accounts for the most debilitating clinical symptoms of Guillain Barré Syndrome (GBS). Our goal is to explore the mechanisms of axon loss in this condition, by testing the hypothesis that axon degeneration in GBS is governed by a defined molecular program amenable for therapeutic intervention.

Specifically we will test whether inactivation of proteins, known to dictate axon loss after experimental injury, affords axon terminal protection in murine models of GBS.

Sphingomyelin dosage in GBS/CIDP patients: biomarker validation in a multicenter, prospective study ; Luana Benedetti, MD, PhD and Lucilla Nobbio, PhD; University of Genova, ITALY The identification of a biomarker specific and sensitive to improve diagnostic accuracy, to monitor disease activity, to stage patients, and to select specific treatments is a prime goal for the GBS/CIDP Community.

Due to the encouraging results we obtained by dosing SM levels in the CSF of patients affected by GBS and CIDP, we propose the present study whose major significance is to validate our results on a sizeable and carefully selected number of patients.

(IGOS) in Switzerland: a deeper look into HEV-induced GBS ; Paolo Ripellino, MD, Neurologist; Neurocenter of Southern Switzerland This study will increase the amount of clinical and prognostic data of the IGOS consortium with the inclusion of patients from an important area located in the middle of Europe. The high quality of the Swiss health care system will allow researchers to obtain accurate data.

The systematic collection of acute phase samples in a biobank will be fundamental for future international, cooperative studies. The subproject about the role of HEV is innovative because – although so far neglected – HEV is an increasing, preventable (by appropriate cooking and blood donors testing) disease and this infection is associated to GBS.

Disease-specific Biomarkers In Inflammatory Neuropathies ; Luis Querol MD PhD; Hospital de la Santa Creu i Sant Pau, Barcelona Inflammatory neuropathies (IN) are disorders in which disease-specific biomarkers are not required or diagnostic purposes, leading to disease heterogeneity. We discovered the association of anti-contactin-1 antibodies to a specific CIDP subset using an unbiased approach.

This strategy has also proven effective in antibodies against NF155 and nodal neurofascins in CIDP, in which our group has also played a central role.

The discovery of paranodal antibodies hasboosted translational research in the field, including the description of specific pathology, genetic background ( DRB1*15 association with NF155 antibodies), response to treatment and animal models, supporting the idea that the classification of IN according to disease-specific biomarkers would make IN research and care more efficient.

Intravenous immunoglobulin and intravenous methylprednisolone as optimal induction treatment in CIDP (OPTIC trial) ; Dr Laura Zambreanu, MD, MRCP; National Hospital for Neurology and Neurosurgery, UK Most CIDP patients are treated with regular intravenous immunoglobulin (IVIg) because of fast improvement and rare adverse events, but IVIg is expensive.

Corticosteroid treatment is associated with longer time to improvement and more side effects, but may lead to long-term remission1,2. We intend to participate in a multicentre, randomized, double-blind, placebo-controlled superiority trial in patients with active CIDP.

The primary objective is to assess whether combining IVIg and intravenous methylprednisolone (IVMP) leads to more frequent long-term remission in CIDP compared to IVIg alone. Patients will be recruited in the Netherlands and the UK.

Enhance peripheral nerve repair by modulating macrophage subsets: ( Gang Zhang, PhD Assistant Professor of Neurology University of Texas, Health Sciences Center at Houston) Synopsis: Autoimmune neuropathies consist of a group of peripheral nerve disorders associated with dysregulation of adaptive and innate immune responses.

Among these disorders, Guillain-Barré syndrome (GBS) is one of the most common causes of acute flaccid paralysis worldwide. Two immune modulating therapies, namely, Intravenous immunoglobulin (IVIg) and plasma exchange, have been developed to treat GBS. However, there are many disadvantages including high cost, supply shortages, and multiple side effects that are usually associated with high dose and long infusion time of IVIg.

Therefore, new therapeutic strategies that can limit the nerve injury during the acute phase of the disease and enhance repair during recovery period are highly desirable. It is in this context we propose a novel therapeutic strategy of modulating macrophage polarization (promote M2 polarization) for treating GBS. Macrophages are central regulators of inflammation.

Probing the role of skin biopsy in CIDP nodo-paranodopathies: (Raffaella Lombardi,1 Jerome Devaux,2 Andrea Cortese,3 Giuseppe Lauria1) Synopsis: CIDP is a heterogeneous pathology that critically lacks of diagnostic and prognostic biomarkers. The recent identification of IgG4 anti-neurofascin 155 (Nfasc155) or anti-contactin 1 (CNTN1) antibodies in a subset of patients has widened the spectrum of CIDP phenotypes.

These patients how disabling tremor, poor response to intravenous immunoglobulin, and distal and sensory disturbances. Cell-adhesion molecule Nfasc155 and CNTN1 are expressed on the paranode, and play key roles on sodium channel clustering and glia-axon interactions.

Our preliminary results on skin biopsies from three IgG4 Nfasc155-positive CIDP patients revealed complete loss of Nfasc155 staining at the paranodes, asymmetrical paranodes and widening of the nodes of dermal myelinated nerve fibers. One IgG4 CNTN1-positive CIDP patient showed abnormal nodal/paranodal immunostaining with different features as compared with IgG4 Nfasc155-positive patients suggesting specific changes.

Flavivirus and arbovirus associated GBS in South East Asia: ( Umapathi Thirugnanam , Senior Consultant Neurologist, National Neuroscience) Synopsis: A number of antecedent infections are associated with Guillain-Barré syndrome (GBS). Recently, symptomatic and asymptomatic Zika virus (ZIKV) infection has been shown to trigger GBS.

In the Southern hemisphere the burden of flavi and other mosquito-borne arbovirus infections such as dengue, chikungunya and Japanese encephalitis is considerable. Even in a small, developed country like Singapore, dengue infections can exceed 20,000 a year. Symptomatic dengue has been documented to antecede GBS.

Recently we reported that asymptomatic dengue could also trigger GBS. In parts of South East Asia, GBS cases increase after rainy season when mosquitos breed and dengue infections are common. The anecdotal experience of doctors working in these region suggests that diarrhea associated GBS is infrequent.

The actual burden of dengue and other arbovirus, including ZikV, associated GBS is uncertain. The ZikV strain responsible for the current epidemic is Asian, described in 1960-70s in South East Asia. It is conceivable that ZikV isendemic in this region.

The serological response to secondary infections in patients previously infected with dengue or other flavivirus may also impact on the propensity for these viruses to induce dysimmunity. These questions on immunopathology of flavivirus and arbovirus related GBS are particularly pertinent as the search for vaccines is intensified and large scale vaccinations are expected shortly.

Effect of Anti-Contactin-1 Antibodies on DRG Neuron: (Dr. Kathrin Doppler MD, Prof. Dr. Claudia Sommer University Hospital Würzburg) Synopsis: Antibodies against the paranodal (excitable area of the axon in between the myelinated sections) protein contactin-1 have been reported in a subgroup of patients with CIDP who have tremor and an unsteady gait. Binding of autoantibodies is proposed to lead to impaired nerve conduction.

Contactin-1 is also expressed by sensory neurons of the dorsal root ganglia (DRG). It is proposed by the applicant that Ab binding to the DRG causes sensory ataxia (unsteady gait) in patients. Anti-contactin-1 Ab decreases the density of sodium channels on DRG neurons.

They therefore hypothesize that binding of anti-contactin-1 to DRG neurons affects the physiology of voltage-gated sodium channels and thus impairs neuronal function.

They will determine the effect of anti-contactin-1 Ab on the function of these sodium channels by patch clamp recordings of living cultured mouse DRG neurons after incubation with patients’ or control IgG prepared from Therapeutic plasma exchange material of patients and controls. Ab binding will be confirmed with a cytochrome labeled second antibody.

Development of a Tolerogenic vaccination for Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): (Cristoforo Comi, MD, PhD. Assistant Professor of Neurology Department of Translational Medicine, University of Piemonte Orientale) Synopsis: CIDP is an autoimmune disease in which peripheral nerve injury reflects both antibody (Ab) and cell-mediated immune responses against peripheral nerve components or antigens (Ags).

Candidate Ags include myelin proteins used to induce experimental autoimmune neuritis (EAN) and nodal/paranodal proteins including contactin-1 and neurofascin. Better knowledge of the spectrum of autoAgs is crucial to develop new specific therapies, such as tolerogenic (or “inverse”) vaccination to turn off the specific immune response.

This lab previously developed a vaccine to Experimental Allergic Encephalomyelitis by using nanoparticles encapsulating both auto Ags and immunomodulatory substances that inhibited experimental autoimmune encephalomyelitis Loss of Schwann cell plasticity in CIDP: A central role for GM-CSF: (Helmar C.

Lehmann, MD Department of Neurology University Hospital of Cologne Kerpener Strasse) Synopsis: Current available therapies in CIDP are aimed to reduce inflammation in affected nerve fibers. However there is no treatment available to enhance regeneration once nerves are injured.

We observed in preliminary experiments that Schwann cells fail to support regeneration of injured nerves when they are exposed to blood components of CIDP patients. Preliminary studies showed a significantly “low expression of cytokine GM-CSF” that might be responsible for the incomplete clinical recovery seen in many CIDP patients.

We propose a set of experiments to characterize the pro-regenerative potential of GM-CSF in more detail and to assess GM-CSF as putative biomarker in CIDP. The medium-term goal is to develop a novel treatment strategy to enhance nerve regeneration in CIDP. Defining the contribution of B cells