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. 2014 Dec 29;178(Suppl 1):124–126. doi: 10.1111/cei.12538

7th International Immunoglobulin Conference: Interlaken Leadership Awards

M C Dalakas *,†, W N Löscher ‡
PMCID: PMC4285518  PMID: 25546789

Abstract

The Interlaken Leadership Awards (ILAs), established in 2010, are monetary grants pledged annually by CSL Behring to fund research into the use of immunoglobulin (Ig) therapy, especially into its use in neurological disorders. Five recipients of the 2011/2012 Awards were invited to present their research at the 7th International Immunoglobulin Conference. Dr Honnorat reports on paraneoplastic neurological syndromes (PNS). His multi-centre Phase II trial, currently under way, will assess the efficacy of IVIg therapy in treating PNS in the first 3 months of treatment. Dr Geis shows improved disease scores after IVIg treatment in a mouse model of neuromyelitis optica (NMO). It is hoped that these promising results will translate well into human NMO. Dr Schmidt studied IVIg therapy in an mdx mouse model for Duchenne muscular dystrophy (DMD). He reports that motor function improved and myopathic changes in skeletal muscles and creatine kinase release were decreased. Dr Gamez presents the design and rationale for a Phase II clinical trial investigating the preoperative use of IVIg therapy in myasthenia gravis patients to prevent post-operative myasthenic crisis. Dr Goebel reports results from studies elucidating the immune-mediated pathogenesis of complex regional pain syndrome (CRPS), the successful IVIg therapy in a proportion of CRPS patients, and the development of a model for predicting which patients are more likely to respond to Ig therapy.

Keywords: complex regional pain syndrome, Duchenne muscular dystrophy, myasthenia gravis, neuromyelitis optica, paraneoplastic neurological syndrome

Introduction

The Interlaken Leadership Awards (ILAs) are research grants awarded annually by CSL Behring to scientists around the world committed to furthering knowledge of the use of immunoglobulin (Ig) therapy. Established in 2010, the programme's mission is to ‘explore novel opportunities to enhance quality of life (QoL) for patients using polyvalent immunoglobulins’ 1. The current focus of the programme is neurological disorders. The papers in this section have been written by recipients of the 2011/2012 ILAs, and detail research into the treatment of neurological disorders with Ig therapy which has been made possible by funding from the Awards.

Findings are presented from research designed or conducted in five different disorders: paraneoplastic neurological syndromes (PNS), neuromyelitis optica (NMO), Duchenne muscular dystrophy (DMD), myasthenia gravis (MG) and complex regional pain syndrome (CRPS). Our understanding of the causes, pathology and specific therapies of these diseases is varied; however, all are seriously debilitating conditions which can leave patients with a very poor QoL.

PNS encompass immune-mediated neurological conditions associated with cancer that affect multiple parts of the central and peripheral nervous system 2. Dr Honnorat presents an overview of the existing retrospective and prospective clinical studies in PNS 3–13, and the rationale for the current Phase II, multi-centre trial investigating the efficacy of intravenous immunoglobulin (IVIg) in their treatment.

Dr Geis has used the Award to study the effects of IVIg therapy in a mouse model of NMO, a central nervous system disease affecting the spinal cord and optic nerve, related to autoantibodies against aquaporin 4 (AQP4) 14. Currently, treatments for NMO focus on removal of the autoantibodies or suppression of their production, B cell depletion or high-dose corticosteroid treatment; data from Dr Geis' study have shown that IVIg treatment ameliorated symptoms in the mouse model, suggesting that treatment with IVIg may be explored as potential therapy in NMO patients.

Unlike the other diseases discussed in this section, DMD is an inherited disorder, caused by mutations in the dystrophin gene on the X chromosome 15, which results not only in degenerative but also reactive inflammatory changes within the muscle. DMD patients experience devastating muscle degeneration and death before their fourth decade. Dr Schmidt and his team tested IVIg therapy in a mouse model for DMD, finding that motor function and muscle contractility were improved and myopathic changes and cellular infiltration were reduced. Whether these results will have any potential applications for the treatment of human disease remains to be determined.

Dr Gamez, the only 2012 Award recipient in this section, is currently recruiting patients to his Phase II clinical trial of IVIg treatment for MG patients undergoing surgery. Procedures such as thymectomies are often required in these patients 16, but the use of general anaesthetic may carry a risk of inducing life-threatening muscle weakness 17. Dr Gamez's study aims to ascertain whether pre-operative treatment with IVIg could be helpful in reducing the occurrence of these myasthenic deteriorations.

Finally, Dr Goebel presents data from his ongoing work looking into the potential uses of IVIg treatment in CRPS. Despite having been a recognized condition for more than a century, CRPS is an extremely complex and previously poorly understood condition where patients experience chronic, ongoing pain with no apparent cause which does not respond to typical pain relief treatments. Data now show that the ongoing pain signal may, at least partially, have an autoimmune pathogenesis, and it has also been shown that a proportion of patients may respond to treatment with IVIg therapy. Dr Goebel's current research focuses on methods that could potentially predict response to Ig or other immunotherapies 18–20.

Acknowledgments

M. C. D. and W. N. L. would like to thank Meridian HealthComms Ltd for providing medical writing services.

Disclosure

M. C. D. has received speaking honoraria or served as a consultant for Novartis, CSL, Genzyme, Baxter, Octapharma, Dysimmue Foundation and Grifols. W. N. L. received project funding, travel support or speaker fees from CSL Behring, Lilly, Astellas, Genzyme, Baxter and Pfizer.

References

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