Compositions for treating insulin deficiency conditions

A technology of insulin deficiency and composition, applied in the direction of drug combination, metabolic disease, endocrine system disease, etc., can solve problems such as high cost, lower quality of life of T1D patients, disability, etc.

Pending Publication Date: 2022-03-01
UNIVERSITY OF GENEVA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Due to this effect, intensive insulin therapy can lead to hypoglycemia, which can lead to disability and sometimes death 12-14
Since insulin therapy does not eradicate the disabling comorbidities of T1D (e.g. heart attack, stroke, blindness, renal failure, neuropathy, etc.), the required cost of T1D care is enormous and comparable to the quality of life of normal subjects. T1D patients have a 15% lower quality of life than

Method used

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  • Compositions for treating insulin deficiency conditions
  • Compositions for treating insulin deficiency conditions
  • Compositions for treating insulin deficiency conditions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0177] result

[0178] Beneficial metabolic effects of enhanced S100A9 in a mouse model of T1D

[0179] The inventors overexpressed S100A9 in insulin-deficient mice. The inventors performed hydrodynamic tail vein injection studies in RIP-DTR mice carrying the rat insulin promoter (RIP) upstream of the diphtheria toxin receptor (DTR) sequence cloned into the X chromosome Hprt locus. After three consecutive intraperitoneal DT administrations, RIP-DTR mice almost completely lost pancreatic β cells. Indeed, in DT-injected RIP-DTR mice subjected to HTVI of pLIVE (DT-pLIVE) or pLIVE-S100A9 (DT-pLIVE-S100A9), nearly all pancreatic β-cells were ablated (data not shown). Consistent with β-cell loss, pancreatic proinsulin mRNA levels were barely measurable, and these defects resulted in barely detectable circulating insulin in DT-pLIVE and DT-pLIVE-S100A9 mice (Fig. 1a, Fig. 1b). To test whether S100A9 was increased in DT-pLIVE-S100A9 mice, we assessed plasma S100A9 levels and found ...

Embodiment 2

[0184] The presence of the C-terminal FLAG sequence did not interfere with the ability of S100A9 to ameliorate ID symptoms in mice.

[0185] To determine whether the addition of a FLAG tag sequence to S100A9 would affect the ability of S100A9 to ameliorate ID symptoms in mice, we overexpressed the full-length native S100a9 sequence (with or without a C-terminal FLAG tag) under the control of the albumin promoter using HTVI delivery. ) plasmid (pLIVE-n-S100A9 or pLIVE-S100A9-FLAG) or control empty vector (pLIVE). DT-treated RIP-DTR mice subjected to HTVI of pLIVE (DT-pLIVE) or pLIVE-n-S100A9 (DT-pLIVE-n-S100A9) or pLIVE-S100A9-FLAG (DT-pLIVE-S100A9-FLAG) 27 showed a similar degree of hypoinsulinemia ( image 3 a). While DT-pLIVE mice exhibited hyperglycemia and hyperketosis, DT-pLIVE-n-S100A9 mice and DT-pLIVE-S100A9-FLAG mice showed similar improvements in these parameters ( image 3 b to image 3 c). These data suggest that the fusion of S100A9 to the FLAG tag sequence doe...

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Abstract

The present disclosure provides compositions and methods for treating an insulin deficiency (ID) disorder or associated symptom in a subject in need thereof, the compositions comprising S100 calcium binding protein A9 (S100A9), a variant or fragment of S100 calcium binding protein A9, and insulin, a variant or fragment of insulin.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority from European Patent Application Serial No. 19183317.7 filed 28 June 2019, the content of which is incorporated herein by reference in its entirety. [0003] sequence listing [0004] The Sequence Listing related to this application is provided in text format in lieu of a paper copy and is hereby incorporated by reference into the specification. The name of the text file containing the sequence listing is PAT7278PC00_ST25.txt. technical field [0005] The present disclosure provides compositions and methods for treating insulin deficiency (ID) disorders or related symptoms in a subject in need thereof, the compositions comprising S100 calcium binding protein A9 (S100A9), S100 calcium binding protein A9 Variants or fragments and insulin, variants or fragments of insulin. Background technique [0006] Tens of millions of people suffer from type 1 diabetes (T1D); a con...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P3/10A61P5/50A61K38/28
CPCA61K38/1709A61P5/50A61P3/10A61K38/28A61K2300/00
Inventor R·科帕里G·拉马多里D·米克罗普洛
Owner UNIVERSITY OF GENEVA
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