What are examples of peptide drugs that are growth factors?

Examples of Peptide Drugs That Are Growth Factors

Peptide growth factors are important therapeutic agents used in various clinical applications, particularly for tissue regeneration, wound healing, and management of neutropenia. Several recombinant human growth factors have been developed as pharmaceutical products with specific clinical indications.

Key Peptide Growth Factor Drugs

Platelet-Derived Growth Factor (PDGF)

• Becaplermin (REGRANEX) is a recombinant human platelet-derived growth factor (rhPDGF-BB) produced by inserting the gene for the B chain of PDGF into yeast (Saccharomyces cerevisiae) 1
• Becaplermin is FDA-approved as a topical gel (100 mcg/g) for treatment of diabetic lower extremity ulcers 1
• rhPDGF-BB promotes chemotactic recruitment and proliferation of cells involved in wound repair and enhances formation of granulation tissue 1
• Clinical applications include treatment of intrabony periodontal defects, furcation defects, and gingival recessions 2

Keratinocyte Growth Factor (KGF)

• Palifermin (Kepivance) is a recombinant human KGF produced in E. coli 3
• It is a truncated form of human KGF (140 amino acids) with the first 23 N-terminal amino acids deleted to improve protein stability 3
• Palifermin binds to KGF receptors on epithelial cells, stimulating proliferation, differentiation, and migration 3
• Used to reduce the incidence and duration of severe oral mucositis in patients undergoing hematopoietic stem cell transplantation 3

Granulocyte Colony-Stimulating Factor (G-CSF)

• Tbo-filgrastim (Granix) is a recombinant G-CSF used to reduce the duration of severe neutropenia in patients receiving myelosuppressive chemotherapy 4
• Indicated for patients receiving chemotherapy with ≥20% risk of developing febrile neutropenia 4
• Administered subcutaneously at 5 mcg/kg/day, starting 24-72 hours after completion of chemotherapy 4

Other Important Growth Factors in Clinical Development

Bone Morphogenetic Proteins (BMPs)

• Recombinant human BMP-2 (rhBMP-2) is used in oral hard and soft tissue regeneration 2
• BMPs 2-4 and BMP-7 stimulate mesenchymal progenitor cell migration and osteoblast differentiation 2
• These growth factors are released by osteoblasts and contribute to bone matrix synthesis 2

Epidermal Growth Factor (EGF)

• EGF promotes proliferation of epithelial and endothelial cells 5
• Has been studied for wound healing applications, though clinical evidence for routine use is limited 2
• Stimulates keratinocyte proliferation in vitro at concentrations of 10-25 ng/mL 5

Fibroblast Growth Factor (FGF)

• FGF-2 (basic FGF) stimulates fibroblast proliferation and plays a role in extracellular matrix synthesis 2
• Clinical studies of basic fibroblast growth factor for diabetic foot ulcers have not supported routine clinical use 2
• FGFs are involved in angiogenesis and have been studied as potential therapeutic targets 6

Vascular Endothelial Growth Factor (VEGF)

• VEGF promotes angiogenesis and has antiapoptotic effects on bone-forming cells 2
• One study of intramuscular injections of a plasmid containing VEGF gene showed promising results on wound area reduction, but requires confirmation before clinical recommendation 2

Clinical Considerations for Growth Factor Therapy

• Growth factors regulate key wound healing events by binding to specific cell receptors and activating intracellular signaling pathways 2
• They are involved in four overlapping wound healing phases: hemostasis, inflammation, granulation, and maturation 2
• The efficacy of growth factor therapy depends on appropriate dosing, timing, and delivery methods 2
• Some growth factors may have synergistic effects when used in combination (e.g., PDGF and IGF-1) 2

Safety Considerations

• Becaplermin carries a warning about increased rate of death from systemic malignancies in patients using 3 or more tubes 1
• Growth factors that stimulate epithelial cell proliferation have theoretical concerns regarding tumor growth 3
• Most peptide growth factors have limited systemic absorption when applied topically 1
• Common adverse effects of G-CSFs include bone pain, which can be managed with nonsteroidal anti-inflammatory drugs 4

Growth factor therapy represents an important area of regenerative medicine, with several peptide drugs already approved and many more in clinical development. The therapeutic application of these molecules continues to expand as our understanding of their mechanisms and optimal delivery methods improves.