A Basic Fibroblast Growth Factor Analog for Protection and Mitigation against Acute Radiation Syndromes

Abstract

The effects of fibroblast growth factors and their potential as broad-spectrum agents to treat and mitigate radiation injury have been studied extensively over the past two decades. This report shows that a peptide mimetic of basic fibroblast growth factor (FGF-P) protects and mitigates against acute radiation syndromes. FGF-P attenuates both sepsis and bleeding in a radiation-induced bone marrow syndrome model and reduces the severity of gastrointestinal and cutaneous syndromes; it should also mitigate combined injuries. FGF-2 and FGF-P induce little or no deleterious inflammation or vascular leakage, which distinguishes them from most other growth factors, angiogenic factors, and cytokines. Although recombinant FGFs have proven safe in several ongoing clinical trials, they are expensive to synthesize, can only be produced in limited quantity, and have limited shelf life. FGF-P mimics the advantageous features of FGF-2 without these disadvantages. This paper shows that FGF-P not only has the potential to be a potent yet safe broad-spectrum medical countermeasure that mitigates acute radiotoxicity but also holds promise for thermal burns, ischemic wound healing, tissue engineering, and stem-cell regeneration.

Radioprotective Agents for Radiation Therapy: Future Trends

“…To date, clinical studies have not documented tumor promotion, but additional studies documenting the risk of epitehelial-drived tumor stimulation are ongoing [18]. Other limitations to the use of recombinant FGFs are their expense, their difficulty to produce in large amounts and their limited shelf life [78]. Development of peptide analogues of FGFs that lack these limitations is underway.…”

“…future science group www.futuremedicine.com Several members of the FGF family have also been documented to protect against radiationinduced damage. Radioprotection of the small bowel in mice has been demonstrated following treatment with both FGF-1 and FGF-2 [75], and Phase II and III studies in humans using human recombinant FGFs have shown promise [78]. In particular, the radioprotective potential of human recombinant FGF-7, also known as recombinant human KGF or palifermin, is currently the focus of much research.…”

“…Development of peptide analogues of FGFs that lack these limitations is underway. A peptide analogue of FGF-2, FGF-P, has recently been documented in mice to attenuate sepsis and bleeding in a radiation-induced bone marrow syndrome model and to reduce the severity of GI and cutaneous syndromes [78].…”

Use of Growth Factors and Cytokines to Treat Injuries Resulting from a Radiation Public Health Emergency

“…Endogenous FGF is found in many tissues in the body, and its levels can vary dramatically. Cost restrictions associated with the use of human recombinant (hrFGF2) led to the development of FGF-P, a 17 amino acid peptide fragment of FGF2 (16).…”

Pharmacoprophylactic and Pharmacotherapeutic Approaches to Mitigating the Damaging Effects of Ionizing Radiation: Review of Information Sources

“…), а також похідні пурину чи піримідину (ксантозин, кофеїн, метилурацил, пентоксил, теофілін та ін.) [19,40,45,7,9,15,49,54].…”