Introduction

An invention is proposed relating to a specific isoform of MnSOD (Mn superoxide dismutase) and its uses for the protection and treatment of subjects exposed to radiation, in particular space radiation. The possible applications of the rMnSOD molecule are both in the space field, for the biological protection and safety of astronauts engaged in space missions of increasing duration and distance from the Earth, and in the terrestrial field, for the biological protection and safety of exposed individuals, or potentially exposed to radiant energies of any nature and intensity, and, in particular, for the amplification of the effectiveness of radiotherapy in the oncological field.

Technical features

The proposed invention shows the radioprotective role of a specific isoform of a human recombinant protein (rMnSOD) which possesses the specific antioxidant and antiradical activity of SOD and which can be easily administered in vivo systemically, reaching and penetrating the cells without requiring further manipulations, unlike other MnSODs which need manipulation to enter cells (e.g.: Cell-penetrating peptide assisted protein delivery; nanoformulation, inclusion in nanovesicles, etc). The effects of rMnSOD were studied in vitro, on irradiated normal and tumor cells, and in vivo, on mice exposed to lethal doses of ionizing radiation. The results demonstrated that rMnSOD exerts:
A radioprotective effect on normal cells (in vitro). On normal MRC-5 cells, irradiation alone induces dose-dependent damage which with 3 Gy of X-rays leads to cell death. The same radiotreatment, in the presence of 0.5 μM of rMnSOD, results in significant radioprotection and cell survival. A radioprotective effect on normal tissue (in vivo), found in cardiac, cervical, kidney, and liver tissue of radiation-treated mice, in the presence or absence of rMnSOD treatment. A radiosensitizing effect for tumor cells (in vitro). On LSA cells (liposarcoma-derived cell line), irradiation with 6 Gy of X-rays alone has no effect on cell survival. Conversely, when LSA cells are irradiated with only 3 Gy, in the presence of 0.5 μM rMnSOD, the cells are killed. Similarly in MCF-7 cells, irradiation with 3 Gy of X-rays alone led to cell death after 14 days, while the same cells were killed when irradiated with only 2 Gy in the presence of 0.5 μM of rMnSOD. Furthermore, while animals treated in the absence of rMnSOD survived no more than 6-7 days after radiation, those treated with rMnSOD survived for a longer period, up to 30 days considered as an experimental time limit.

Possible Applications

• Protection from radiation to which man is subject during space missions (e.g. cosmic rays).
• Protection from radiations present on the ground (e.g. sun, uranium, radioactive isotopes for radiodiagnostics, etc.).
• Application in the medical field in the field of radiodiagnostics and oncological radiotherapy (protection of healthy tissue from radiation-induced damage and radiosensitizing effect for tumor cells)

Advantages

• Protection from radiation present in the space environment
• Protection from radiation present on the ground
• Amplification of the effectiveness of radiation oncology
• No manipulation (e.g.: Cell-penetrating peptide assisted protein delivery; nanoformulation, inclusion in nanovesicles, etc) is required for its administration