Compositions comprising ENO1 and their use in methods of treating obesity or overweight and reducing weight gain

A technology of weight gain and composition, applied in the field of reducing or preventing weight gain of objects, obesity of objects, and can solve problems such as weight gain of patients

Inactive Publication Date: 2018-03-27
BERG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

For example, treatment of type 2 diabetes with rosiglitazone (Avandia) or sulfonylureas causes patients to gain weight

Method used

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  • Compositions comprising ENO1 and their use in methods of treating obesity or overweight and reducing weight gain
  • Compositions comprising ENO1 and their use in methods of treating obesity or overweight and reducing weight gain
  • Compositions comprising ENO1 and their use in methods of treating obesity or overweight and reducing weight gain

Examples

Experimental program
Comparison scheme
Effect test

example 7 and 8

[0119] The optimal ratio of dendrimer to Eno1 in the complex can be determined using any conventional method known in the art (e.g., pyruvate kinase (PK) / lactate dehydrogenase (LDH) assay or any of the methods described herein. Other assays) were tested and selected by analyzing the Eno1 activity of the dendrimer / Eno1 complex (eg, compared to non-complexed Eno1). The optimal ratio of dendrimer to Eno1 can also be assessed by measuring the glucose uptake in human skeletal muscle myotubes (HSMM), for example as described in Example 2 or any similar assay known in the art. Compounds were tested and selected for their effect on glucose uptake in in vitro assays. The optimal ratio of dendrimer to Eno1 can also be measured, for example, as described in Examples 7 and 8 of US2015 / 0361409 (which are incorporated herein by reference in their entirety) or any similar model or analysis known in the art. The effect of dendrimer / Eno1 complexes on blood glucose in a mouse model of diabetes...

example 1

[0172] Example 1: Reduction of body weight gain by treatment with muscle-targeted Eno1 / dendrimer complex and rosiglitazone in a db / db mouse genetic model of obesity

[0173] Muscle-targeted Eno1 / dendrimer complexes were generated to analyze their efficacy in reducing body weight gain. The dendrimer complex comprises human Eno1, transcript variant 1 protein (SEQ ID NO:2), which is non-covalently linked to a G5-PAMAM dendrimer / muscle targeting peptide (MTP) (ASSLNIA; SEQ ID NO: 7) Conjugates. A stock solution of Eno1 was prepared in buffer, and the protein solution was mixed with the G5 dendrimer-MTP conjugate.

[0174] Lean mice and male obese and diabetic db / db mice (male BKS.Cg-m+ / +Lepr db / J mice) were obtained from commercial suppliers. All mice were housed 2 to 3 per cage on a 12h:12h day-dark cycle at 22°C and acclimated to a standard diet for 3 weeks at the animal facility. At 8 weeks of age, Eno1 was given 200 μg / kg body weight twice daily by subcutaneous injection ...

example 2

[0182] Example 2: Generation of detectably labeled PAMAM dendrimers, muscle targeting Eno1

[0183] Detectably labeled muscle targeting Eno1 was generated to analyze its efficacy in targeting to muscle cells. Detectably labeled G5-PAMAM dendrimers containing the muscle targeting peptide (MTP) ASSLNIA and / or Eno1 were generated using the method described below. A range of different ratios of MTP to dendrimers was evaluated, including MTPs containing dendrimers containing about 10 MTP peptides per dendrimer, about 3 MTP peptides per dendrimer, or Body about 1 MTP peptide.

[0184] The procedure for preparing Eno1 dendrimer complexes involves identifying optimal ratios and concentrations of reagents. A stock solution of Eno1 was prepared in buffer, and the protein solution was mixed with G5 dendritic muscle targeting peptide (MTP) conjugate at different ratios. A range of different ratios of dendrimers to Eno1 were also evaluated, including Eno1 containing dendrimers containin...

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Abstract

The invention provides a method for reducing or preventing body weight gain in a subject comprising administering to the subject enolase 1 (Eno1). The invention also provides methods of treating obesity, and of reducing body weight in a subject afflicted with an overweight condition, comprising administering to the subject enolase 1 (Eno1). In certain embodiments, the body weight gain, obesity oroverweight condition is caused by a therapeutic treatment, such as a diabetic drug. In certain methods of the invention, the Eno1 is delivered to muscle.

Description

[0001] related application [0002] This application claims the benefit of US Provisional Patent Application No. 62 / 182,966, filed June 22, 2015, the contents of which are incorporated herein in their entirety. [0003] Submit sequence listing [0004] The Sequence Listing associated with this application is submitted in electronic format via EFS-Web and is hereby incorporated by reference in its entirety into this specification. The name of the text file containing the sequence listing is 119992_14802_Sequence_Listing. The size of the text file is 15KB, and the text file was created on June 22, 2016. Background technique [0005] Obesity is a major public health problem in developed countries. Obesity is also increasing in developing countries and affects younger populations. For example, obesity affects more than 20% of men and more than 25% of women in the United States. Have a body mass index (BMI = weight (kg) / height) greater than or equal to 30 2 (m 2 )) are consi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61P3/04A61P3/10
CPCA61K9/127A61K47/595A61K47/62A61K38/51C12Y402/01011A61K9/0053A61K9/0019A61P3/04A61P3/10
Inventor N·R·纳莱恩R·萨兰加拉詹V·K·维什纽达斯S·吉斯塔E·景
Owner BERG
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