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“Tremendous advances in our understanding of pathogenesis of amyotrophic lateral sclerosis (ALS) have provided a

rich pipeline of drugs for clinical trialists. At least 32 unique compounds have been tested. Nevertheless, riluzole is currently the only treatment that prolongs survival. We present a critical overview of past clinical trials, how therapies are selected for testing in people, challenges with ALS clinical trial design and conduct, and ways to best move forward.”
“This review focuses Selonsertib on recent data regarding inflammatory demyelinating neuropathies and neuropathies associated with monoclonal gammopathies. We describe both acute and chronic inflammatory neuropathies, and we discuss conditions ranging from mostly cell-mediated to antibody-mediated disorders. These diseases are characterized

by proximal and distal sensory motor involvement. Treatments are based on immune-modulation and/or immune-suppression. Work-up sequence and therapeutical modes are discussed in the light of recently published data, with a special interest on new treatment modalities.”
“Myasthenia gravis (MG) is a prototypic antibody-mediated neurological autoimmune disorder. Herein we characterize modern treatment algorithms that are adapted to disease severity, and introduce the current principles of escalating strategies for MG treatment. In non-thymoma patients younger than about 50 years of age and with generalized weakness, a complete early (but not AMP deaminase urgent) Selleckchem Roscovitine thymectomy is considered as state-of-the-art on the basis of circumstantial evidence and expert opinion. In up to 10% of patients, MG is associated with a thymoma (i.e., is of paraneoplastic origin). The best surgical type of procedure is still under debate.

Myasthenic crisis is best treated by plasmapheresis, mostly

combined with immunoabsorption techniques. Intravenous immunoglobulins are a reasonable alternative, but a shortage in supplies and high prices limit their use. In generalized MG, a wide array of immunosuppressive treatments has been established, although not formally tested in double-blind, prospective trials. With regard to immunosuppression, azathioprine is still the standard baseline treatment, often combined with initial corticosteroids. In rare patients with an inborn hepatic enzyme deficiency of thiomethylation, azathioprine may be substituted by mycophenolate mofetil. Severe cases may benefit from combined immunosuppression with corticosteroids, cyclosporine A, and even with moderate doses of methotrexate or cyclophosphamide. Tacrolimus is under investigation.

In refractory cases, immunoablation via high-dose cyclophosphamide followed by trophic factors such as granulocyte colony-stimulating factor has also been suggested. In the future we may face an increased use of novel, B-cell, or T-cell directed monoclonal antibodies.