ArticleDiabetologia2010
Intradermal alpha1-antitrypsin therapy avoids fatal anaphylaxis, prevents type 1 diabetes and reverses hyperglycaemia in the NOD mouse model of the disease.
Article in Diabetologia, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (GlassiaInternational journal of molecular sciences · 2019Trial
- Alpha 1 Antitrypsin Suppresses Autoantibody Production and Cellular Autoimmunity in Chronic Graft-Versus-Host Disease (cGVHD) in a Lupus Mouse Model.Biomolecules · 2026Article
- The Inhibitory Effects of Alpha 1 Antitrypsin on Endosomal TLR Signaling Pathways.Biomolecules · 2025Article
- Skewed adaptive immune responses are involved in alpha-1 antitrypsin deficiency emphysema.The European respiratory journal · 2025Article
- Alpha-1 Antitrypsin Reduces Disease Progression in a Mouse Model of Charcot-Marie-Tooth Type 1A: A Role for Decreased Inflammation and ADAM-17 Inhibition.International journal of molecular sciences · 2022Article
- Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes.Developmental cell · 2021Article
- Transgenic Mice Overexpressing Human Alpha-1 Antitrypsin Exhibit Low Blood Pressure and Altered Epithelial Transport Mechanisms in the Inactive and Active Cycles.Frontiers in physiology · 2021Article
- Association between α1-antitrypsin and acute coronary syndrome.Experimental and therapeutic medicine · 2020Article
- Alpha-1-Antitrypsin Ameliorates Pristane Induced Diffuse Alveolar Hemorrhage in Mice.Journal of clinical medicine · 2019Article
- Regulated hAAT Expression from a Novel rAAV Vector and Its Application in the Prevention of Type 1 Diabetes.Journal of clinical medicine · 2019Article
- Alpha 1 Antitrypsin Gene Therapy Extends the Lifespan of Lupus-Prone Mice.Molecular therapy. Methods & clinical development · 2018Article
- Alpha-1 Antitrypsin Therapy for Autoimmune Disorders.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- Anti-inflammaging effects of human alpha-1 antitrypsin.Aging cell · 2018Article
- Targeting Innate Immunity for Type 1 Diabetes Prevention.Current diabetes reports · 2017Review
- Alpha-1 antitrypsin inhibits RANKL-induced osteoclast formation and functions.Molecular medicine (Cambridge, Mass.) · 2017Article
- iTRAQ-Based Proteomics of Chronic Renal Failure Rats after FuShengong Decoction Treatment Reveals Haptoglobin and Alpha-1-Antitrypsin as Potential Biomarkers.Evidence-based complementary and alternative medicine : eCAM · 2017Article
- Exploration of α1-antitrypsin treatment protocol for islet transplantation: dosing plan and route of administration.The Journal of pharmacology and experimental therapeutics · 2016Article
- Alpha 1 Antitrypsin Inhibits Dendritic Cell Activation and Attenuates Nephritis in a Mouse Model of Lupus.PloS one · 2016Article
- TAK1 inhibition prevents the development of autoimmune diabetes in NOD mice.Scientific reports · 2015Article
- Immune protective effect of human alpha-1-antitrypsin gene during β cell transplantation in diabetic mice.Immunologic research · 2015Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
aims/hypothesisHuman alpha1-antitrypsin (hAAT) gene therapy prevents type 1 diabetes in a NOD mouse model of diabetes. However, repeated i.p. injections of hAAT into NOD mice leads to fatal anaphylaxis. The aim of the study was to determine if an alternative route of administration avoids anaphylaxis and allows evaluation of hAAT's potential for diabetes prevention and reversal. We also sought to determine if the addition of granulocyte colony-stimulating factor (G-CSF), augments hAAT's capacity to prevent or reverse disease in the NOD mice.
methodsTo evaluate hAAT pharmacokinetics, serum hAAT levels were monitored in NOD mice receiving a single dose (2 mg) of hAAT by i.p., s.c. or i.d. injection. For studies of type 1 diabetes prevention and reversal, mice received i.d. hAAT (2 mg/mouse/3 days) for 8 or 10 weeks or hAAT and G-CSF (i.p., 6 microg/day) for 6 weeks. Blood glucose determinations, glucose tolerance testing and insulin tolerance tests were performed.
resultsBoth i.p. and s.c. injections resulted in fatal anaphylaxis. The i.d. injection avoided anaphylaxis and i.d. injection of hAAT into 11-week-old NOD mice prevented disease (p = 0.005, AAT vs PBS at 40 weeks of age). Treatment of diabetic NOD mice with hAAT or hAAT plus G-CSF provided long-term (at least 100 days) reversal of diabetes in 50% of treated animals. G-CSF did not enhance the reversal rates of hAAT. Glucose tolerance and insulin levels were normalised in mice with hAAT prevention and reversal. CONCLUSIONS/
interpretationIntradermal hAAT prevents and reverses disease in a NOD mouse model of type 1 diabetes without inducing anaphylaxis.
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Registered trials
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