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Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination
Published on: September 12, 2016
Daclizumab and its use in multiple sclerosis treatment
1Department of Neurology, Barzilai University Medical Center, Ashkelon, Faculty of Health Sciences, Ben-Gurion University of the Negev, Ashkelon, Israel. ronm@bmc.gov.il.
Abstract:
Daclizumab is a humanized monoclonal antibody that binds to the a-subunit (CD25) of the interleukin-2 receptor (IL-2R), thus blocking the formation of the high-affinity IL-2R which is expressed mainly on activated and regulatory T cells. IL-2R modulation by daclizumab results primarily in the expansion of regulatory CD56(bright) natural killer cells that are capable of killing activated T cells, rather than direct suppression of activated T cells. The pharmacokinetic profile of its currently available form, daclizumab high-yield process (DAC-HYP, Zinbryta), suggests high subcutaneous bioavailability, linear pharmacokinetics and an effective half-life suitable for monthly administration. A comprehensive clinical program in relapsing-remitting multiple sclerosis demonstrated an impressive effect of DAC-HYP on inflammatory and clinical disease activity compared with placebo or interferon beta, which led to its recent approval for the treatment of relapsing forms of multiple sclerosis. Several serious adverse events and risks call for the implementation of a risk management program in multiple sclerosis patients treated with DAC-HYP.
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