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Treatment of Type 2 Diabetes With FTY720

a type 2 diabetes and fty720 technology, applied in the field of type 2 diabetes (t2d), can solve the problems of t2d risk, new cases of blindness among adults, non-traumatic lower limb amputation, etc., and achieve the effects of reducing insulin levels, preserving or increasing the mass of functional beta-cells, and treating poor glycemic control

Inactive Publication Date: 2014-04-17
DIAPIN THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes a new treatment for Type 2 diabetes (T2D) using a medication called FTY720, which is already FDA-approved for relapsing multiple sclerosis (MS). FTY720 is taken as an oral pill, is easy to tolerate, and has potential to cure T2D. It also promotes beta-cell regeneration with low risk of tumorigenesis. The patent discusses the safety profile of FTY720 and its use in treating relapsing MS without any reports of cancer formation. Overall, this patent highlights the technical effects of FTY720 as a promising treatment for T2D.

Problems solved by technology

Diabetes is the leading cause of kidney failure, non-traumatic lower-limb amputation, and new cases of blindness among adults in the United States.
Without intervention and appropriate treatment, people with prediabetes are at risk for developing T2D.
Although some anti-diabetic drugs may positively affect beta-cells, there are few effective therapeutic approaches proposed to target beta-cell mass expansion.

Method used

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  • Treatment of Type 2 Diabetes With FTY720
  • Treatment of Type 2 Diabetes With FTY720
  • Treatment of Type 2 Diabetes With FTY720

Examples

Experimental program
Comparison scheme
Effect test

example 1

Oral Administration of FTY720 to Db / Db Mice Normalizes Hyperglycemia without Affecting Insulin Sensitivity

[0085]To rigorously determine the effects of FTY720 in vivo, pre-diabetic (age of six weeks, fasting glucose <126 mg / dL) and diabetic (age of 8-9 weeks, fasting glucose=430 mg / dL) female db / db mice were fed daily with FTY720 (+FTY720) for 29 weeks, and monitored by weekly fasting blood glucose measurements. It was demonstrated that the fasting glucose levels in the FTY720-treated pre-diabetic db / db mice remained normal (˜126 mg / dL) and in diabetic db / db mice (glucose ≧350 mg / dL) also became normal after six weeks of FTY720-treatment whereas fasting glucose levels increased significantly in the untreated group (−FTY720) by the age of eight weeks and continued to increase over time (to about 500 mg / dL by the age of 12 weeks) (FIG. 2A).

[0086]Importantly, this well controlled fasting glucose levels over time occurred despite the fact that FTY720 administration was ceased completely ...

example 2

FTY720 Treatment Increases Beta-Cell Mass in Db / Db Mice

[0090]Islets were isolated from 8 weeks old normal C57 / BL6 mice and treated with or without 0.2 μM FTY720 in the culture medium without FBA for 24 hours. Then the islets were stimulated with glucose and secreted insulin was measured using an Ultra Sensitive Mouse Insulin ELISA Kit (Crystal Chem Inc., Downers Grove, Ill.) and total proteins of islets were measured. FTY720 does not affect glucose-stimulated insulin secretion ex vivo in the isolated pancreatic islets (FIG. 6).

[0091]Because FTY720 treatment increased fasting insulin levels in the db / db mice (FIG. 4) and did not affect the glucose-stimulated insulin secretion ex vivo (FIG. 7), the islet morphology, size and insulin content in pancreases were compared between the two groups of animals. Both hematoxylin and eosin (H&E) staining (FIG. 7) and immunohistochemical staining for insulin (FIG. 8) indicated that the untreated db / db mice experienced deterioration in islet morph...

experiment 3

FTY720 Treatment Activates PI3K Signaling Pathway in Db / Db Islets

[0096]Expression of pancreatic and duodenal homeobox 1 (PDX-1), a transcription factor, is required for pancreatic development and β-cell maturation. This invention demonstrated that the PDX-1 expression in the islets from the FTY720-treated db / db mice was 6-fold higher than that in the islets from the untreated mice consistent with PI3K activation (FIG. 14). These data provide evidence that oral administration of FTY720 significantly increases the expression of pancreatic and duodenal homeobox 1 (PDX-1) in the islets of the db / db mice.

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PUM

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Abstract

The present disclosure provides therapeutic methods for prevention and treatment of type-2 diabetes comprising administering to the subject an effective amount of FTY720 or an analog.

Description

CROSS-REFERENCE TO RELATED APPLICATION[0001]This application is a continuation of U.S. application Ser. No. 13 / 722,495, filed Dec. 20, 2012, which is a continuation of PCT Application No. PCT / US2012 / 049565, filed on Aug. 3, 2012, which claims priority to U.S. Provisional Application Ser. No. 61 / 574,441, filed Aug. 3, 2011. The entire content of these applications are incorporated herein by reference.STATEMENT OF FEDERAL SUPPORT[0002]This invention was made with government support under grant number NS063962 awarded by the National Institute of Health. The government has certain rights in the invention.FIELD[0003]The present invention relates generally to the field of type-2 diabetes (T2D). More particularly, the present invention concerns method for treating prediabetes and for preventing and treating type T2D.BACKGROUND OF THE INVENTION[0004]Diabetes is a group of metabolic diseases characterized by high levels of blood glucose levels (≧126 mg / dL or 7.0 mmol / L). The three most comm...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/28A61K31/661C07F9/09A61K31/138C07C215/30A61K45/06
CPCA61K38/28C07C215/30A61K31/661C07F9/094A61K31/138A61K45/06A61K31/137A61P43/00A61P3/10
Inventor MA, ZHONGMIN
Owner DIAPIN THERAPEUTICS
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