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LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus

Canine Diabetes (CD) is identical to human T1DM. Helper T cells expressing the CD40 receptor (TH40) are prominent in human T1DM. TH40 cell expansions occur regardless of HLA haplotype or auto-antibody status and remain elevated throughout disease. TH40 cells from T1DM respond to human islets, TH40 f...

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Autores principales: Wagner, David, Vaitaitis, Gisela, Waid, Dan, Webb, Craig, Webb, Tracy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9625042/
http://dx.doi.org/10.1210/jendso/bvac150.611
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author Wagner, David
Vaitaitis, Gisela
Waid, Dan
Webb, Craig
Webb, Tracy
author_facet Wagner, David
Vaitaitis, Gisela
Waid, Dan
Webb, Craig
Webb, Tracy
author_sort Wagner, David
collection PubMed
description Canine Diabetes (CD) is identical to human T1DM. Helper T cells expressing the CD40 receptor (TH40) are prominent in human T1DM. TH40 cell expansions occur regardless of HLA haplotype or auto-antibody status and remain elevated throughout disease. TH40 cells from T1DM respond to human islets, TH40 from healthy controls do not. At a Veterinary Hospital 6 female and 2 male dogs that met clinical criteria for T1DM were recruited. Physical exam, blood panels and CBC were done. Dogs were dosed with a OPT501 a drug targeting CD40 mediated inflammation by IV infusion. Doses were 2 and later 4 mg/kg, given on days 1, 4, 7, then weekly for 8 weeks. Diabetic dogs had significantly elevated TH40 numbers compared to non-diabetic dogs (p < 0. 0001). OPT501 reduced TH40 cell numbers to normal, following which insulin requirements reduced on average by 75% and up to 90%. The canine equivalent of HbA1c reduced 40.2% on average; 3 subjects were normal range. Daily blood glucose reduced significantly, 3 subjects maintained normal glucose levels. Time-in-range (TIR) increased to up to 90%, from a previous 10%. Increased c - peptide levels were universally detected after 8 weeks of treatment. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
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spelling pubmed-96250422022-11-14 LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus Wagner, David Vaitaitis, Gisela Waid, Dan Webb, Craig Webb, Tracy J Endocr Soc Diabetes & Glucose Metabolism Canine Diabetes (CD) is identical to human T1DM. Helper T cells expressing the CD40 receptor (TH40) are prominent in human T1DM. TH40 cell expansions occur regardless of HLA haplotype or auto-antibody status and remain elevated throughout disease. TH40 cells from T1DM respond to human islets, TH40 from healthy controls do not. At a Veterinary Hospital 6 female and 2 male dogs that met clinical criteria for T1DM were recruited. Physical exam, blood panels and CBC were done. Dogs were dosed with a OPT501 a drug targeting CD40 mediated inflammation by IV infusion. Doses were 2 and later 4 mg/kg, given on days 1, 4, 7, then weekly for 8 weeks. Diabetic dogs had significantly elevated TH40 numbers compared to non-diabetic dogs (p < 0. 0001). OPT501 reduced TH40 cell numbers to normal, following which insulin requirements reduced on average by 75% and up to 90%. The canine equivalent of HbA1c reduced 40.2% on average; 3 subjects were normal range. Daily blood glucose reduced significantly, 3 subjects maintained normal glucose levels. Time-in-range (TIR) increased to up to 90%, from a previous 10%. Increased c - peptide levels were universally detected after 8 weeks of treatment. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m. Oxford University Press 2022-11-01 /pmc/articles/PMC9625042/ http://dx.doi.org/10.1210/jendso/bvac150.611 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Diabetes & Glucose Metabolism
Wagner, David
Vaitaitis, Gisela
Waid, Dan
Webb, Craig
Webb, Tracy
LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus
title LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus
title_full LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus
title_fullStr LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus
title_full_unstemmed LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus
title_short LBSUN332 A Novel Drug To Modulate Auto-inflammation And Promote Glucose Control In Type 1 Diabetes Mellitus
title_sort lbsun332 a novel drug to modulate auto-inflammation and promote glucose control in type 1 diabetes mellitus
topic Diabetes & Glucose Metabolism
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9625042/
http://dx.doi.org/10.1210/jendso/bvac150.611
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