This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. If the Autoimmune response in Type I diabetes, mediated by T-helper Type 1 (Th1) cells and their secreted cytokines including IFN-y, TNF-a and IL-2, could be modulated prior to B cell destruction, insulin deficiency might be prevented. Daclizumab (Zenapax), a humanized IgG1 monoclonal antibody specific for IL-2 receptor, functions as a receptor antagonist. Its 20 day half-life permits IV drug dosing every 2-3 weeks. Daclizumab is approved for prevention of acute renal allograft rejections. No toxicity has been demonstrated as measured by rates of systemic infusion reaction, nephrotoxicity, infections, or malignancies with three years of follow-up. We propose an open label trial to test the safety and efficacy of daclizumab in children with partial residual B cell function. One hundred children, ages 1-16 years, will be recruited into the two year trial and randomized either to conventional therapy or conventional treatment in combination with daclizumab. Efficacy will be assessed by duration of the honeymoon period, dose of insulin, HgA1C, glycated albumin levels, C-peptide levels, fasting insulin to glucose ratios and IVGTT. Immunologic efficacy will include assessment of CD25 expression in peripheral blood, islet cell, insulin and GAD antibodies, and in vitro T cell proliferative response to GAD. Safety will be monitored by assessing infusion-related toxicities, frequency and type of infections, development of daclizumab antibodies, and chemistry and hematological profiles. If a clinical response is not demonstrated by 6 months, daclizumab will be discontinued, but efficacy and safety parameters will be monitored for the duration of the study.
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