ArticleDiabetes2010
Virtual optimization of nasal insulin therapy predicts immunization frequency to be crucial for diabetes protection.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Role of the PD-1/PD-L1 Dyad in the Maintenance of Pancreatic Immune Tolerance for Prevention of Type 1 Diabetes.Frontiers in endocrinology · 2020Review
- Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Article
- Optimal Tolerogenic Dendritic Cells in Type 1 Diabetes (T1D) Therapy: What Can We Learn From Non-obese Diabetic (NOD) Mouse Models?Frontiers in immunology · 2019Review
- Quantitative Systems Pharmacology: A Case for Disease Models.Clinical pharmacology and therapeutics · 2017Article
- A model qualification method for mechanistic physiological QSP models to support model-informed drug development.CPT: pharmacometrics & systems pharmacology · 2016Article
- In silico model-based inference: an emerging approach for inverse problems in engineering better medicines.Current opinion in chemical engineering · 2015Article
- Agent-Based Modeling in Systems Pharmacology.CPT: pharmacometrics & systems pharmacology · 2015Article
- Article
- Enhancing the discovery and development of immunotherapies for cancer using quantitative and systems pharmacology: Interleukin-12 as a case study.Journal for immunotherapy of cancer · 2015Review
- Autoreactive T cells specific for insulin B:11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice.PloS one · 2014Article
- Trials in type 1 diabetes: Antigen-specific therapies.Clinical immunology (Orlando, Fla.) · 2013Review
- Progress in immune-based therapies for type 1 diabetes.Clinical and experimental immunology · 2013Review
- Preexisting autoantibodies predict efficacy of oral insulin to cure autoimmune diabetes in combination with anti-CD3.Diabetes · 2012Article
- Clinical potential of antigen-specific therapies in type 1 diabetes.The review of diabetic studies : RDS · 2012Review
- Antigen-specific prevention of type 1 diabetes in NOD mice is ameliorated by OX40 agonist treatment.Journal of autoimmunity · 2011Article
- Insulin as a key autoantigen in the development of type 1 diabetes.Diabetes/metabolism research and reviews · 2011Review
- 2011 Update: antigen-specific therapy in type 1 diabetes.Current opinion in endocrinology, diabetes, and obesity · 2011Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveDevelopment of antigen-specific strategies to treat or prevent type 1 diabetes has been slow and difficult because of the lack of experimental tools and defined biomarkers that account for the underlying therapeutic mechanisms. RESEARCH DESIGN AND
methodsThe type 1 diabetes PhysioLab platform, a large-scale mathematical model of disease pathogenesis in the nonobese diabetic (NOD) mouse, was used to investigate the possible mechanisms underlying the efficacy of nasal insulin B:9-23 peptide therapy. The experimental aim was to evaluate the impact of dose, frequency of administration, and age at treatment on Treg induction and optimal therapeutic outcome.
resultsIn virtual NOD mice, treatment efficacy was predicted to depend primarily on the immunization frequency and stage of the disease and to a lesser extent on the dose. Whereas low-frequency immunization protected from diabetes atrributed to Treg and interleukin (IL)-10 induction in the pancreas 1-2 weeks after treatment, high-frequency immunization failed. These predictions were confirmed with wet-lab approaches, where only low-frequency immunization started at an early disease stage in the NOD mouse resulted in significant protection from diabetes by inducing IL-10 and Treg.
conclusionsHere, the advantage of applying computer modeling in optimizing the therapeutic efficacy of nasal insulin immunotherapy was confirmed. In silico modeling was able to streamline the experimental design and to identify the particular time frame at which biomarkers associated with protection in live NODs were induced. These results support the development and application of humanized platforms for the design of clinical trials (i.e., for the ongoing nasal insulin prevention studies).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.