publication . Article . 2016

Exploration of α1-Antitrypsin Treatment Protocol for Islet Transplantation: Dosing Plan and Route of Administration

Baranovski, Boris M.; Ozeri, Eyal; Shahaf, Galit; Ochayon, David E.; Schuster, Ronen; Bahar, Nofar; Kalay, Noa; Cal, Pablo; Mizrahi, Mark I.; Nisim, Omer; ...
Open Access English
  • Published: 01 Dec 2016 Journal: The Journal of Pharmacology and Experimental Therapeutics, volume 359, issue 3, pages 482-490 (issn: 0022-3565, eissn: 1521-0103, Copyright policy)
  • Publisher: The American Society for Pharmacology and Experimental Therapeutics
Abstract
Lifelong weekly infusions of human α1-antitrypsin (hAAT) are currently administered as augmentation therapy for patients with genetic AAT deficiency (AATD). Several recent clinical trials attempt to extend hAAT therapy to conditions outside AATD, including type 1 diabetes. Because the endpoint for AATD is primarily the reduction of risk for pulmonary emphysema, the present study explores hAAT dose protocols and routes of administration in attempt to optimize hAAT therapy for islet-related injury. Islet-grafted mice were treated with hAAT (Glassia; intraperitoneally or subcutaneously) under an array of clinically relevant dosing plans. Serum hAAT and immunocyte c...
Subjects
free text keywords: Inflammation, Immunopharmacology, and Asthma
46 references, page 1 of 4

Ashkenazi E Baranovski BM Shahaf G Lewis EC (2013) Pancreatic islet xenograft survival in mice is extended by a combination of alpha-1-antitrypsin and single-dose anti-CD4/CD8 therapy. PLoS One 8:e63625.23717456 [OpenAIRE] [PubMed]

Austin GE Mullins RH Morin LG (1987) Non-enzymic glycation of individual plasma proteins in normoglycemic and hyperglycemic patients. Clin Chem 33:2220–2224.3690840 [PubMed]

Balbi B Ferrarotti I Miravitlles M (2016) Efficacy of augmentation therapy for emphysema associated with α1-antitrypsin deficiency: enough is enough. Eur Respir J 47:35–38.26721962 [PubMed]

Braza F Brouard S Chadban S Goldstein DR (2016) Role of TLRs and DAMPs in allograft inflammation and transplant outcomes. Nat Rev Nephrol 12:281–290.27026348 [PubMed]

Daemen MA Heemskerk VH van’t Veer C Denecker G Wolfs TG Vandenabeele P Buurman WA (2000) Functional protection by acute phase proteins alpha(1)-acid glycoprotein and alpha(1)-antitrypsin against ischemia/reperfusion injury by preventing apoptosis and inflammation. Circulation 102:1420–1426.10993862 [PubMed]

Dhami R Zay K Gilks B Porter S Wright JL Churg A (1999) Pulmonary epithelial expression of human alpha1-antitrypsin in transgenic mice results in delivery of alpha1-antitrypsin protein to the interstitium. J Mol Med (Berl) 77:377–385.10353442 [PubMed]

Ehlers MR (2014) Immune-modulating effects of alpha-1 antitrypsin. Biol Chem 395:1187–1193.24854541 [OpenAIRE] [PubMed]

Elshikha AS Lu Y Chen MJ Akbar M Zeumer L Ritter A Elghamry H Mahdi MA Morel L Song S (2016) Alpha 1 antitrypsin inhibits dendritic cell activation and attenuates nephritis in a mouse model of lupus. PLoS One 11:e0156583.27232337 [OpenAIRE] [PubMed]

Feng Y Hu L Xu Q Yuan H Ba L He Y Che H (2015) Cytoprotective role of alpha-1 antitrypsin in vascular endothelial cell under hypoxia/reoxygenation condition. J Cardiovasc Pharmacol 66:96–107.25815674 [PubMed]

Feng Y Xu J Zhou Q Wang R Liu N Wu Y Yuan H Che H (2016) Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress. Front Physiol 7:176.27303303 [OpenAIRE] [PubMed]

Finotti P Pagetta A (2004) A heat shock protein70 fusion protein with alpha1-antitrypsin in plasma of type 1 diabetic subjects. Biochem Biophys Res Commun 315:297–305.14766207 [PubMed]

Fleixo-Lima G Ventura H Medini M Bar L Strauss P Lewis EC (2014) Mechanistic evidence in support of alpha1-antitrypsin as a therapeutic approach for type 1 diabetes. J Diabetes Sci Technol 8:1193–1203.25155845 [OpenAIRE] [PubMed]

Flotte TR Trapnell BC Humphries M Carey B Calcedo R Rouhani F Campbell-Thompson M Yachnis AT Sandhaus RA McElvaney NG (2011) Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results. Hum Gene Ther 22:1239–1247.21609134 [OpenAIRE] [PubMed]

Gao W, Zhao J, Kim H, Xu S, Chen M, Bai X, Toba H, Cho HR, Zhang H, Keshavjeel S (2014) alpha1-Antitrypsin inhibits ischemia reperfusion-induced lung injury by reducing inflammatory response and cell death. J Heart Lung Transplant 33:309–315.24365768 [PubMed]

Gottlieb PA Alkanani AK Michels AW Lewis EC Shapiro L Dinarello CA Zipris D (2014) α1-Antitrypsin therapy downregulates toll-like receptor-induced IL-1β responses in monocytes and myeloid dendritic cells and may improve islet function in recently diagnosed patients with type 1 diabetes. J Clin Endocrinol Metab 99:E1418–E1426.24527714 [OpenAIRE] [PubMed]

46 references, page 1 of 4
Abstract
Lifelong weekly infusions of human α1-antitrypsin (hAAT) are currently administered as augmentation therapy for patients with genetic AAT deficiency (AATD). Several recent clinical trials attempt to extend hAAT therapy to conditions outside AATD, including type 1 diabetes. Because the endpoint for AATD is primarily the reduction of risk for pulmonary emphysema, the present study explores hAAT dose protocols and routes of administration in attempt to optimize hAAT therapy for islet-related injury. Islet-grafted mice were treated with hAAT (Glassia; intraperitoneally or subcutaneously) under an array of clinically relevant dosing plans. Serum hAAT and immunocyte c...
Subjects
free text keywords: Inflammation, Immunopharmacology, and Asthma
46 references, page 1 of 4

Ashkenazi E Baranovski BM Shahaf G Lewis EC (2013) Pancreatic islet xenograft survival in mice is extended by a combination of alpha-1-antitrypsin and single-dose anti-CD4/CD8 therapy. PLoS One 8:e63625.23717456 [OpenAIRE] [PubMed]

Austin GE Mullins RH Morin LG (1987) Non-enzymic glycation of individual plasma proteins in normoglycemic and hyperglycemic patients. Clin Chem 33:2220–2224.3690840 [PubMed]

Balbi B Ferrarotti I Miravitlles M (2016) Efficacy of augmentation therapy for emphysema associated with α1-antitrypsin deficiency: enough is enough. Eur Respir J 47:35–38.26721962 [PubMed]

Braza F Brouard S Chadban S Goldstein DR (2016) Role of TLRs and DAMPs in allograft inflammation and transplant outcomes. Nat Rev Nephrol 12:281–290.27026348 [PubMed]

Daemen MA Heemskerk VH van’t Veer C Denecker G Wolfs TG Vandenabeele P Buurman WA (2000) Functional protection by acute phase proteins alpha(1)-acid glycoprotein and alpha(1)-antitrypsin against ischemia/reperfusion injury by preventing apoptosis and inflammation. Circulation 102:1420–1426.10993862 [PubMed]

Dhami R Zay K Gilks B Porter S Wright JL Churg A (1999) Pulmonary epithelial expression of human alpha1-antitrypsin in transgenic mice results in delivery of alpha1-antitrypsin protein to the interstitium. J Mol Med (Berl) 77:377–385.10353442 [PubMed]

Ehlers MR (2014) Immune-modulating effects of alpha-1 antitrypsin. Biol Chem 395:1187–1193.24854541 [OpenAIRE] [PubMed]

Elshikha AS Lu Y Chen MJ Akbar M Zeumer L Ritter A Elghamry H Mahdi MA Morel L Song S (2016) Alpha 1 antitrypsin inhibits dendritic cell activation and attenuates nephritis in a mouse model of lupus. PLoS One 11:e0156583.27232337 [OpenAIRE] [PubMed]

Feng Y Hu L Xu Q Yuan H Ba L He Y Che H (2015) Cytoprotective role of alpha-1 antitrypsin in vascular endothelial cell under hypoxia/reoxygenation condition. J Cardiovasc Pharmacol 66:96–107.25815674 [PubMed]

Feng Y Xu J Zhou Q Wang R Liu N Wu Y Yuan H Che H (2016) Alpha-1 antitrypsin prevents the development of preeclampsia through suppression of oxidative stress. Front Physiol 7:176.27303303 [OpenAIRE] [PubMed]

Finotti P Pagetta A (2004) A heat shock protein70 fusion protein with alpha1-antitrypsin in plasma of type 1 diabetic subjects. Biochem Biophys Res Commun 315:297–305.14766207 [PubMed]

Fleixo-Lima G Ventura H Medini M Bar L Strauss P Lewis EC (2014) Mechanistic evidence in support of alpha1-antitrypsin as a therapeutic approach for type 1 diabetes. J Diabetes Sci Technol 8:1193–1203.25155845 [OpenAIRE] [PubMed]

Flotte TR Trapnell BC Humphries M Carey B Calcedo R Rouhani F Campbell-Thompson M Yachnis AT Sandhaus RA McElvaney NG (2011) Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results. Hum Gene Ther 22:1239–1247.21609134 [OpenAIRE] [PubMed]

Gao W, Zhao J, Kim H, Xu S, Chen M, Bai X, Toba H, Cho HR, Zhang H, Keshavjeel S (2014) alpha1-Antitrypsin inhibits ischemia reperfusion-induced lung injury by reducing inflammatory response and cell death. J Heart Lung Transplant 33:309–315.24365768 [PubMed]

Gottlieb PA Alkanani AK Michels AW Lewis EC Shapiro L Dinarello CA Zipris D (2014) α1-Antitrypsin therapy downregulates toll-like receptor-induced IL-1β responses in monocytes and myeloid dendritic cells and may improve islet function in recently diagnosed patients with type 1 diabetes. J Clin Endocrinol Metab 99:E1418–E1426.24527714 [OpenAIRE] [PubMed]

46 references, page 1 of 4
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