Image courtesy of Pickpik.
Space radiation poses a massive danger to astronauts. Out in the depths of space, astronauts are constantly exposed to high-energy particles called galactic cosmic rays, placing them at risk of life-threatening radiation sickness and even cancer. This past June, a collaboration of scientists from across the world published an article in Nature showing evidence that drugs called antagomirs might reverse the harmful effects of space radiation.
Antagomirs are inhibitors of microRNAs (miRNAs), which are small RNA fragments. miRNAs have significant control over which genes are transcribed: a single miRNA molecule can silence the expression of hundreds to thousands of genes. By inhibiting specific miRNAs with antagomirs, the researchers hypothesize that they could restore the normal function of genes involved in DNA repair, mitigating the damage caused by cosmic rays.
Based on previous research in cancer biology, the researchers already knew how to use patterns in miRNA expression data to hunt for specific miRNAs that might be responsible for spaceflight-related damage. “With cancer, there is a persistent signal in your body that systemically causes damage but also helps the cancer grow, allowing a constant miRNA signature to be present,” said Afshin Beheshti, director of the Space Biomedicine Program at the University of Pittsburgh and key researcher on the study. Previously, Beheshti identified thirteen of these miRNAs specifically associated with damage from space radiation, but in this paper, he narrowed down his targets to three specific types.
The researchers then tested if a mix of the specific antagomirs inhibiting these three miRNAs could combat the effects of space radiation in a 3D human microvascular tissue model. The tissues were exposed to simulated deep-space radiation of 0.5 Gy (a unit of measurement of radiation absorption), mimicking the accumulated dose an astronaut would encounter on a round-trip mission to Mars. The experiments overall displayed decreased inflammation, restoration of mitochondrial function, and fewer DNA double-strand breaks, which are all critical to maintaining cellular health and resilience. These findings were further validated with actual biological samples from astronaut missions, such as Inspiration4, NASA’s first all-civilian commercial mission, and missions involving Japanese Aerospace Exploration Agency astronauts, which showed that the same three miRNAs were altered in human spaceflight participants. These results suggest that antagomir treatment could be used as an effective measure for protecting astronauts from radiation-associated health risks.
Currently, Beheshti is exploring the use of already FDA-approved drugs to target miRNA-induced radiation damage, while seeking funding to initiate clinical human trials. He also aims to experiment with different antagomir delivery methods to prolong the treatment’s effectiveness.
Beyond space exploration, the researchers hope to use their understanding of miRNA therapy to develop new methods for cancer prevention. In the future, miRNA signatures might serve as a powerful diagnostic tool for a range of diseases. Beheshti believes miRNA testing should be implemented into routine annual blood work of a patient, allowing doctors to easily detect the early signs of a developing disease. Once doctors identify high levels of miRNAs associated with different diseases, they can use inhibitor molecules such as antagomirs to bring miRNA levels back to normal. “This, in theory, should stop the disease from progressing,” Beheshti said.