Nome del progetto:
Radioprotective sod soluble isoform and its uses
Stato: Idea
Data di creazione: 14-03-2023
Obbiettivi del progetto:
Short summary
An Italian governmental agency developed the invention of a Mn superoxide dismutase (MnSOD) and its uses for protecting subjects exposed to radiation, in particular, space radiation. The possible applications of the rMnSOD molecule are suited for space: biological protection of astronauts (increasing duration and distance from Earth) and in the terrestrial field, for the biological protection of individuals exposed to radiant energies and particularly for subjects undergoing cancer radio-therapy
Full description The superoxide dismutase (SOD) family of proteins is necessary to protect oxygen-utilizing cells from the toxicity of the reactive oxygen species (ROS) produced during normal metabolism. Besides being protective proteins, these enzymes are also key components of signalling pathways that regulate cell physiology. SODs catalyze the reaction: with hydrogen peroxide being then removed by catalases (CATs) and peroxidases, of which glutathione peroxidase (GPX) has been the most widely studied. The Superoxide dismutase are enzymes of remarkable pharmacological interest for their potential role in the prevention of all pathologies involving oxidative damage. These enzymes can be useful in the prevention and in the treatment of damages caused by physical agents and, particularly by ionizing radiations which generate high levels of free radicals. The large scientific and practical interest towards MnSOD has resulted in intensive developments of new technologies for its production but, despite great efforts, efficient production of recombinant human SOD in prokaryotic systems or simple eukaryotes failed. This failure has so far hindered its large-scale production and protein genetic engineering. The proposed invention shows the radio-protective role of a specific isoform of a human recombinant protein (rMnSOD) which possesses the specific SOD antioxidative and antiradical activity and which can be easily administrated in vivo through the systemic pathway, reaching and penetrating into the cells, without requiring any additional manipulation. rMnSOD effects were studied in vitro, on irradiated normal and cancer cells, and in vivo, on mice exposed to lethal doses of ionizing radiations. The results demonstrated that rMnSOD exerts a radio-protective effect on normal cells (in vitro) and on normal tissues (in vivo) while it is radiosensitizing for cancer cells (in vitro). Moreover, while the animals treated in the absence of rMnSOD would survive no longer than 6-7 days after radiations, those treated with rMnSOD survived for a much longer period up to 30 days considered as the experimental time point. In conclusion, the data derived from experimental testing clearly indicate that the rMnSOD provides a radio-protection for normal cells and confirm also a radio-protective effect of MnSOD. At the same time, the rMnSOD was radio-sensitizing for tumour cells, and both the effects resulted statistically significant. Such data could lead to direct applications in clinical practice, especially because the molecule does not require any manipulation to be safely injected into organisms. Its therapeutic potentiality, as well as the possibility to prevent the damages generated by exposure of normal cells to ionizing radiations, indicate that the rMnSOD deserves to be considered as a tool to amplify the effects of cancer radio-therapy, increasing their specific and selective effect on cancer cells and, at the same time to provide a protection to the organism daily or accidentally exposed to ionizing radiations.
Advantages and innovations
Contact / source: NEXT EEN Widgets (europa.eu)
Full description The superoxide dismutase (SOD) family of proteins is necessary to protect oxygen-utilizing cells from the toxicity of the reactive oxygen species (ROS) produced during normal metabolism. Besides being protective proteins, these enzymes are also key components of signalling pathways that regulate cell physiology. SODs catalyze the reaction: with hydrogen peroxide being then removed by catalases (CATs) and peroxidases, of which glutathione peroxidase (GPX) has been the most widely studied. The Superoxide dismutase are enzymes of remarkable pharmacological interest for their potential role in the prevention of all pathologies involving oxidative damage. These enzymes can be useful in the prevention and in the treatment of damages caused by physical agents and, particularly by ionizing radiations which generate high levels of free radicals. The large scientific and practical interest towards MnSOD has resulted in intensive developments of new technologies for its production but, despite great efforts, efficient production of recombinant human SOD in prokaryotic systems or simple eukaryotes failed. This failure has so far hindered its large-scale production and protein genetic engineering. The proposed invention shows the radio-protective role of a specific isoform of a human recombinant protein (rMnSOD) which possesses the specific SOD antioxidative and antiradical activity and which can be easily administrated in vivo through the systemic pathway, reaching and penetrating into the cells, without requiring any additional manipulation. rMnSOD effects were studied in vitro, on irradiated normal and cancer cells, and in vivo, on mice exposed to lethal doses of ionizing radiations. The results demonstrated that rMnSOD exerts a radio-protective effect on normal cells (in vitro) and on normal tissues (in vivo) while it is radiosensitizing for cancer cells (in vitro). Moreover, while the animals treated in the absence of rMnSOD would survive no longer than 6-7 days after radiations, those treated with rMnSOD survived for a much longer period up to 30 days considered as the experimental time point. In conclusion, the data derived from experimental testing clearly indicate that the rMnSOD provides a radio-protection for normal cells and confirm also a radio-protective effect of MnSOD. At the same time, the rMnSOD was radio-sensitizing for tumour cells, and both the effects resulted statistically significant. Such data could lead to direct applications in clinical practice, especially because the molecule does not require any manipulation to be safely injected into organisms. Its therapeutic potentiality, as well as the possibility to prevent the damages generated by exposure of normal cells to ionizing radiations, indicate that the rMnSOD deserves to be considered as a tool to amplify the effects of cancer radio-therapy, increasing their specific and selective effect on cancer cells and, at the same time to provide a protection to the organism daily or accidentally exposed to ionizing radiations.
Advantages and innovations
- Protection of a subject from exposure to radiations, either in space or terrestrial environment (e.g. sun, uranium, radioactive isotopes for radio-diagnostics, radio-therapy etc.)
- Amplification of the effectiveness of cancer radio-therapy
- Does not require any manipulation to be safely injected into organisms
Contact / source: NEXT EEN Widgets (europa.eu)
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