Pharmacological studies of RGTA₁₁, a heparan sulfate mimetic polymer, efficient on muscle regeneration

Abstract

RGTA is a family of chemically modified polymers that have been engineered to mimic the properties of heparan sulfates towards heparin binding growth factors. In vivo, RGTA stimulated tissue repair and protection when injected at the site of an injury. These properties have been reported in various models, suggesting a potential interest for therapeutic uses as a general tissue repair agent. We have focused our interest on RGTA(11), a dextran derivative that was shown to enhance, after a unique and local administration, muscle regeneration after total crushing. We first show that a single RGTA(11) systemic administration can be as efficient as a local injection for stimulating muscle regeneration. Using an H(3)-labeled RGTA(11) we have measured some pharmacokinetic parameters. Distribution volume was 51.81 mL, clearance was about 2 mL/min, and half-life was 94 min, giving a total elimination time of 11 h. We also demonstrate that RGTA(11) remains detectable in the body only after tissue injury. It was detected by autoradiography in the crushed muscle just after injury and remained at least for a week. These results provide a rational explanation for the long lasting effect of a single local or systemic injection of RGTA.

An Engineered Biopolymer Prevents Mucositis Induced by 5-Fluorouracil in Hamsters

“…Protection of basement membrane integrity by RG1503 has been reported also in a model of ischemic muscle healing. 25 We found in an earlier study that RG1503 enhanced type III collagen deposition within the epithelium basement membrane of periodontal pockets in hamsters. 7 As laminin and type IV collagen are heparin-binding molecules, 26 RG1503 may also mimic the properties of heparan sulfate toward these molecules.…”

A Synthetic Glycosaminoglycan Mimetic Binds Vascular Endothelial Growth Factor and Modulates Angiogenesis

“…They are obtained by grafting specific amounts of carboxylate and sulfate groups onto a dextran backbone. These molecules stimulate tissue repair when applied to the site of injury or systemically (16). They expedite healing of skin (17), bone (18,19), colonic (20), and corneal (21) injuries and have at least 10 time less anticoagulant activity than does heparin.…”

Anabolic Steroids Reduce Muscle Damage Caused by Rotator Cuff Tendon Release in an Experimental Study in Rabbits

“…There are substances that have an anabolic effect on muscle and could potentially counteract the formation of interfiber gaps induced by atrophy, which are known to be filled with fat. Several pharmacological substances influence the development, growth, and repair mechanisms of muscle, namely, anabolic steroids [11][12][13][14][15][16][17][18][19][20] , growth hormones [21][22][23][24] , b-2 agonists, heparan sulfate 25 , xanthine derivatives 26 , creatine 27 , and vitamin D 28 . Of all of these substances, anabolic steroids seem best suited for clinical application.…”