Plasmid encoding fibroblast growth factor for the treatment of hypercholesterolemia or diabetes associated angiogenic defects

A technique for hypercholesterolemia and fibroblasts, applied in the field of promoting collateral angiogenesis in ischemic myocardium or skeletal tissue, collateral vessels and arterioles in ischemic tissue, and can solve the problem of collateral vessel reversal, failure Convincingly proven, inability to improve blood flow, etc.

Inactive Publication Date: 2006-09-13
AVENTIS PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0025] At this point, known therapeutic angiogenesis has not been convincingly demonstrated when tested in a rabbit model of hypercholesterolemia that underwent femoral artery resection, as collateral vessel formation was observed to be impaired following VEGF administration. damage and capillary density were partially reversed (26)
Furthermore, therapeutic angiogenesis has not been convincingly demonstrated when tested in diabetic models, as Roguin A. et al. (Cardiovascular Diabetology 2003, 2:18) found in diabetic ischemic mice using Plasmids expressing VEGF do not enhance blood flow nor promote collateral formation

Method used

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  • Plasmid encoding fibroblast growth factor for the treatment of hypercholesterolemia or diabetes associated angiogenic defects
  • Plasmid encoding fibroblast growth factor for the treatment of hypercholesterolemia or diabetes associated angiogenic defects
  • Plasmid encoding fibroblast growth factor for the treatment of hypercholesterolemia or diabetes associated angiogenic defects

Examples

Experimental program
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Effect test

Embodiment 1

[0122] Example 1: Animals and their diets

[0123] 11-12 week old Syrian golden hamsters (n=50) (CERJ, Le Genest St Isle, France) were used in this experiment. Animals were allowed to equilibrate in a standard environment at least 7 days prior to the start of the experimental protocol. All animals had free access to water throughout the experiment. All animal procedures were approved by the Animal Use committee of Aventis Pharma and performed in accordance with guidelines published by the National Institutes of Health. (NIH Publication No. 85-23, revised 1985).

[0124] In Experiment 1, hamsters (n=37) were randomly divided into 3 groups ( figure 1 ). Low cholesterol group (LC) hamsters (n=13) were fed ad libitum with standard chow (cf. A04-C, UAR, Epinay-sur-Orge, France). For hamsters in two high cholesterol (HC) groups, 21 days (HC / 21) and 28 days after treatment (HC / 28) respectively (HC / 21: n=12; HC / 28: n=12) were given daily 20 g per animal of a cholesterol-enriched...

Embodiment 2

[0125] Example 2: Induction of lower extremity ischemia

[0126] After 35 days of LC or HC feeding, animals were susceptible to lower limb ischemia following surgical procedures as described below. Inducing lower extremity ischemia with N 2 O(0.81.min -1 ), O2 (0.41.min -1 ) and isoflurane (2%) gas anesthesia, following procedures used in other animal species. In a sterile surgical setting, make a longitudinal incision on the medial aspect of the right lower extremity, from the inguinal ligament to the point proximal to the patella. Through this incision, using surgical loops, the femoral artery is isolated and its main branches are coagulated. The femoral artery is completely cut off, its proximal end is the origin of the branch from the external iliac artery, and its distal end is where it divides into two branches, the saphenous artery and the popliteal artery (20). The incision was closed in a single layer with 4.0 silk suture.

Embodiment 3

[0127] Example 3: Gene transfer of lower extremity skeletal muscle

[0128] In Experiment 2, 14 days after the induction of ischemia, the saline group (n=5) or the plasmid group encoding NV1FGF (180 gag DNA, n=8) were blindly given 3 injections, 50 μL each time, and the injection sites were respectively in the ischemic area. Tibialis cranialis, adductors and quadriceps of the lower extremities.

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Abstract

The present invention relates to the use of a plasmid encoding a fibroblast growth factor as therapeutic agent for the prevention and treatment of hypercholesterolemia or diabetes associated myocardial or skeletal angiogenic defects. The present invention also relates to a method for enhancing formation of both collateral blood vessels and arterioles in myocardial or skeletal ischemic tissues in a mammalian subject suffering from hypercholesterolemia or diabetes. The present invention further relates to a method of promoting collateral blood vessels in ischemic myocardial or skeletal tissues without inducing VEGF-A factor expression and causing edema in the treated muscles.

Description

technical field [0001] The present invention relates to the application of the plasmid encoding fibroblast growth factor as a therapeutic drug for preventing and treating myocardial or bone angiogenesis defect related to hypercholesterolemia (hyperchelesterolemia) or diabetes (diabetes). The present invention also relates to methods for enhancing collateral vessel and arteriolerogenesis of ischemic tissue of the myocardium and bone in a mammalian subject suffering from hypercholesterolemia or diabetes. The present invention further relates to a method of promoting collateral angiogenesis in ischemic myocardium or skeletal tissue, which method does not induce VEGF-A factor expression nor cause edema of the treated muscle. Background technique [0002] Blood vessels form a closed blood supply that begins and ends in the heart and includes three main types of blood vessels, arteries, capillaries, and veins. As the heart beats, blood is forced from the ventricles into the aorta...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K38/18A61P9/10A61K31/727
Inventor 亚历克西斯·卡伦弗洛伦斯·伊曼纽尔安妮·卡伦弗朗科伊斯·菲尼尔斯桑德林·米歇莱特伯特兰德·施瓦茨迪迪尔·劳伊迪迪尔·布拉尼利克
Owner AVENTIS PHARMA INC
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