US 2026/0169008 A1 · BIOMARKER FOR TYPE 1 DIABETES

Abstract

In islets collected from female NOD mice at 10, 12, and 14 weeks of age, there was a time-restricted upregulation of proteins involved in the maintenance of β cell function and stress mitigation, followed by loss of expression of these protective proteins that heralded diabetes onset. Pathway analysis showed modulation of EIF2 signaling, the unfolded protein response, mTOR signaling, mitochondrial function, and oxidative phosphorylation during disease progression in NOD mice and in the acute adoptive transfer model, highlighting the importance of this core set of pathways in TID pathogenesis. In immunofluorescence validation studies, β cell expression of protein disulfide isomerase A1 (PDIA1) and 14-3-3b were found to be increased during disease progression in NOD islets, while PDIA1 plasma levels were increased in pre-diabetic NOD mice and in the serum of children with recent-onset TID compared to age and sex-matched non-diabetic controls.

Claims21

Dependent claims

A method of identifying a biomarker associated with early onset type 1 diabetes in humans, said method comprising:

performing a first analysis of a proteome of islets from female NOD mice at three pre-diabetic time points and at a time of diabetes onset;
performing a second analysis of proteome of islets from diabetic NOD mice and NOD-SCID mice that has been rendered acutely diabetic following an adoptive transfer of T cells from NOD.BDC2.5 mice;
performing a third analysis of islets from NOD mice that remained diabetes-free after a time period of observation;
and
identifying a murine biomarker based on the first, second, and third analysis;
and
using the murine biomarker as the biomarker associated with early onset type 1 diabetes in humans before administering a type 1 diabetes preventative therapeutic.

4 more elements

Dependencies are inferred from the claim text.

Biomarker for type 1 diabetes

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Biomarker for type 1 diabetes

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Abstract

Claims21