Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Treating type i and type ii diabetes

a type i and diabetes technology, applied in the field of diabetes treatment methods and materials, can solve the problems of life-threatening hypoglycemia, fatal hypoglycemia, and rare achievement, and achieve the effects of reducing or avoiding fatal hypoglycemia, reducing or eliminating fatal hypoglycemia, and improving quality of li

Inactive Publication Date: 2016-07-07
MAYO FOUND FOR MEDICAL EDUCATION & RES
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The methods and materials provided in this patent can allow clinicians to treat diabetes using an effective insulin gene therapy approach. This approach allows the clinician to control the number of genetically modified insulin-producing cells, which ensures that adequate amounts of insulin are produced while reducing or avoiding insulin overproduction and fatal hypoglycemia. This can replace the daily injections of insulin used by patients with severe type II diabetes. The methods and materials provided can also be used to release vector-encoded insulin continuously at a steady rate, providing better quality of life, compliance with therapy, glycemic control, lower HbA 1c levels, and fewer diabetic complications for diabetes patients.

Problems solved by technology

The goal of therapy is normoglycemia, which minimizes the risk of long-term and short-term complications, but this is rarely achieved despite multiple daily insulin injections, insulin infusion pumps, tight dietary controls, and careful insulin dose calculations based on frequent blood glucose monitoring.
At the other extreme, excess insulin causes life-threatening hypoglycemia.
For example, intramuscular delivery of AAV1 vectors encoding furin-activatable human insulin can normalize blood glucose in diabetic mice, but overdosing can cause fatal hypoglycemia.
Likewise, hydrodynamic liver-directed delivery of sleeping beauty vectors encoding furin-activatable human insulin can normalize blood glucose in diabetic mice, but overdosing can cause fatal hypoglycemia.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Treating type i and type ii diabetes
  • Treating type i and type ii diabetes
  • Treating type i and type ii diabetes

Examples

Experimental program
Comparison scheme
Effect test

example 1

Insulin Gene Therapy for Diabetes

[0034]Nucleic acid encoding human preproinsulin was designed such that the proprotein convertase cleavage signals at the B / C and C / A peptide junctions were modified to allow recognition and cleavage by furin, which is present in the Golgi compartment of most mammalian cells. Briefly, the B / C and C / A cleavage signals were mutated, respectively, from KTTR to RQKR and from LQKR to RQKR (FIG. 1). As a result of these modifications, the expressed preproinsulin polypeptide is processed to functional insulin in the Golgi apparatus of most mammalian cell types and then released by the cell into the extracellular medium.

[0035]Initially, AAV1 or sleeping beauty (SB) vectors encoding a furin-activatable proinsulin without an iC9 death switch were used (FIG. 1). Intramuscular administration of the AAV1-insulin vector to mice with streptozotocin-induced diabetes led to a dose-dependent reduction in the blood glucose level, but caused fatal hypoglycemia at higher ...

example 2

Safety Studies of AAV-insulin-iC9 in Mice

[0039]The optimal vector dose is determined in mice. Experimental diabetes is induced in 8-week-old C57B1 / 6 mice by multiple intraperitoneal injections of streptozotocin (50 mg / kg) resuspended in 0.1 M citrate buffer (pH 4.5) over the course of five days. Fasting blood glucose levels are monitored bi-weekly by FreeStyle Lite Blood Glucose Monitor (Abbott, Ill., USA). Two weeks after diabetes induction, groups of diabetic mice (n=6) receive increasing doses of AAV1-INS-iCasp9 (2.5×1011, 5×1011, 1×1012, 2×1012, 4×1012, 8×1012, 1.6×1013, and 3.2×1013 vg / kg in 200 μL of saline) distributed into tibialis cranealis, gastrocnemius and quadriceps muscles of both hindlimbs. Control groups are non-STZ-treated and STZ-treated mice treated with saline. The mice are monitored for body weight, plasma insulin, c-peptide, and blood glucose levels in the morning and evening and glucose responsiveness through glucose challenge for four weeks after AAV1 adminis...

example 3

Safety Studies of AAV-insulin-iC9 in Non-Human Primates

[0043]Cynomolgus macaques are exposed to streptozotocin (STZ) for diabetes induction followed by disease characterization and then application of AAV1-insulin-iC9 gene therapy for safety and efficacy evaluations. All animals are euthanized at the completion of study and undergo full necropsy. In both the pre and post-STZ phase, animals are screened for baseline characteristics including CBC, chemistry (CPK inclusion required), and HA1c. Blood glucose is measured at least twice daily in the morning (pre prandial) and evening (post prandial). A metabolic panel including c-peptide, IVGTT, AST, MMTT, and 8 hour standard glucose curve is performed. AAV1-ins-IC9 is administered by multiple intramuscular injections unilaterally in the leg muscle under general anesthesia. Dosing is as follows (in genome copies per kilogram): 10e12 (NHP#1), 2×10e12 (NHP#2), or 4×10e12 (NHP#3) using a Quadra-Fuse needle (or equivalent) injection device at...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

This document provides methods and materials for treating diabetes. For example, methods and materials for using nucleic acid encoding human preproinsulin to treat diabetes (e.g., type I or type II diabetes) are provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application Serial No. 61 / 870,537, filed Aug. 27, 2013. The disclosure of the prior application is considered part of (and is incorporated by reference in) the disclosure of this application.BACKGROUND[0002]1. Technical Field[0003]This document relates to methods and materials for treating diabetes. For example, this document provides methods and materials for using nucleic acid encoding human preproinsulin to treat diabetes (e.g., type I or type II diabetes).[0004]2. Background Information[0005]Insulin replacement therapy is the mainstay of treatment for all patients with type I diabetes and for many patients with type II diabetes. The goal of therapy is normoglycemia, which minimizes the risk of long-term and short-term complications, but this is rarely achieved despite multiple daily insulin injections, insulin infusion pumps, tight dietary controls, and careful insulin dose calcu...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C07K14/62A61K31/4545C12N7/00A61K48/00C12N15/85C12N15/86
CPCC07K14/62C12N15/85C12N15/86C12N7/00C12N2800/90A61K31/4545A61K38/00C12N2750/14143C12N2840/203A61K48/005A61P3/10C12N9/6472C12N2830/20
Inventor RUSSELL, STEPHEN JAMES
Owner MAYO FOUND FOR MEDICAL EDUCATION & RES
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com