ABSTRACT
Published studies have described a number of physiological properties and cellular functions of thymosin beta4 (Tbeta4), the major G-actin-sequestering molecule in mammalian cells. Those activities include the promotion of cell migration, blood vessel formation, cell survival, stem cell differentiation, the modulation of cytokines, chemokines, and specific proteases, the upregulation of matrix molecules and gene expression, and the downregulation of a major nuclear transcription factor. Such properties have provided the scientific rationale for a number of ongoing and planned dermal, corneal, cardiac clinical trials evaluating the tissue protective, regenerative and repair potential of Tbeta4, and direction for future clinical applications in the treatment of diseases of the central nervous system, lung inflammatory disease, and sepsis. A special emphasis is placed on the development of Tbeta4 in the treatment of patients with ST elevation myocardial infarction in combination with percutaneous coronary intervention.
Subject(s)
Actins/metabolism , Cell Movement/physiology , Thymosin , Wound Healing/physiology , Actins/genetics , Actins/physiology , Animals , Cell Movement/genetics , Cell Nucleus/genetics , Cell Nucleus/metabolism , Cell Nucleus/physiology , Cell Survival/genetics , Cell Survival/physiology , Chemokines/genetics , Chemokines/metabolism , Chemokines/physiology , Down-Regulation , Heart/physiology , Humans , Mice , Thymosin/chemistry , Thymosin/metabolism , Thymosin/physiology , Up-Regulation , Wound Healing/geneticsABSTRACT
Neurotrophic corneal defects are difficult to heal and all too often lead to scarring and vision loss. Medical management is often of limited success. We describe the results of nine patients (ages 37-84) with chronic nonhealing neurotrophic corneal epithelial defects who were treated with thymosin beta 4 (Tbeta4) sterile eye drops for 28 or 49 days with a follow-up period of 30 days. Those with geographic defects (six patients) showed dramatic healing without clinically significant neovascularization. Stromal thinning was observed in one patient. Three patients with punctate epithelial defects did not have a demonstrable change in their clinical findings. Reduced ocular irritation was reported by all patients soon after treatment initiation. Results from these compassionate use cases indicate that Tbeta4 may provide a novel, topical approach to wound healing in chronic nonhealing neurotrophic corneal ulcers.
