COMMENTARY

One Giant Leap: Space Radiation Research May Help Astronauts and Patients Alike

David M. Warmflash, MD

Disclosures

March 12, 2019

The writers of Star Trek once imagined that in the 22nd century, a drug named "hyronalin" would be invented to treat and prevent radiation's biological effects, something that in the real world we call "acute radiation syndrome" and "chronic radiation sequelae." Although it facilitated humanity's expansion into the galaxy, the fictional hyronalin was developed to save earthbound humans in the wake of an atomic holocaust.

In our current universe, the National Aeronautics and Space Administration (NASA) is seeking antiradiation therapies, driven primarily by a goal to return astronauts to the Moon and eventually to create a human presence on Mars and worlds beyond. One way that NASA is doing this is by funding a translational medicine program called Biomedical Research Advances for Space Health (BRASH) 1801, consisting of several research categories, including the development of nucleic acid therapies for mitigating damage from space radiation.

A Primer on Deep Space Radiation

Since the advent of spaceflight in the 1950s, nearly all piloted missions have taken place in low Earth orbit, where exposure to the most damaging ionizing space radiation is fairly minimal. This is because molten iron flowing in Earth's outer core causes a dynamo effect, producing a magnetic field (the geomagnetosphere) that prevents charged particle radiation from penetrating below certain altitudes—especially over equatorial to temperate latitudes, where most spacecraft orbit. In deflecting charged particles away from their course toward Earth, the geomagnetosphere also traps the particles in regions known as the "Van Allen radiation belts."

Deep space radiation is categorized into three types[1]:

  • Trapped radiation consists of particles trapped in belts, which have particular geometries. To minimize the radiation dosage during Project Apollo, NASA sent lunar-bound astronauts rapidly through only the corner of the inner belt, and through a relatively narrow region of the outer belt.

  • Solar particle events (SPEs) consist mostly of protons. They impart very high radiation doses to any vessel that gets in their way, but they occur intermittently on an 11-year cycle of solar activity, and are low linear energy transfer (LET), so astronauts can be shielded.

  • Galactic cosmic radiation (GCR) comes from outside the solar system. The potential dosage imparted to space travelers is substantially less than that of an SPE, but GCR is present constantly; contains high-energy protons, helium nuclei, and nuclei of higher atomic numbers (HZE particles); and is high LET, so shielding is impractical.

Space is also full of nondeflectable radiation, including neutrons and gamma rays, but charged particles are the main medical concern, because of their high relative biological effectiveness. Considering all types of space radiation, accounting for radiation measurements taken by probes in deep space, it is estimated that astronauts on a 3-year Mars mission could receive a full Sievert of radiation, which could double if SPE activity is high.

New Dangers Stimulate New Research

For some time, NASA has run an open-source database project called GeneLab aimed at helping researchers to elucidate various aspects of the biomolecular effects of the spaceflight environment. In recent years, however, accumulating evidence has indicated that ionizing radiation, particularly charged particles, can produce molecular and cellular damage leading to cancer,[2] cardiovascular disease,[3] and other complications. This led NASA, as part of its Translational Research Institute for Space Health, to make detection and mitigation of space radiation damage a major component of the BRASH 1801 grant program, the purpose of which is to promote space health. Among 15 projects that began BRASH 1801 grants on January 1 of this year, four were chosen for goals aimed at intervening in the effects of space radiation on humans, whereas some others are addressing radiation issues involving plants and pharmaceuticals.

Standard treatments for acute radiation syndrome include supportive measures and also focus on replacement of critical body components that high-dose ionizing radiation destroys, such as leukocytes.[4] Such treatments thus include granulocyte-colony stimulating factor to confront neutropenia and hematopoietic stem cell transplantation, but these do not correct the underlying damage.

Treatments for Astronauts May Help Earthbound Patients As Well

Aiming to mitigate radiation effects at the molecular level, BRASH-funded approaches to human radiation issues include gene therapy. As when gene therapy is used to treat genetic diseases, it can involve use of vectors to carry DNA strands into cells. But other nucleic acid approaches to radiation damage are also taking center stage. In particular, micro-RNAs (miRNAs), RNA strands in the range of 22 bases long, appear promising.

"There has been recent attention on how miRNAs are involved with radiation effects, and even more surprising is that miRNAs might be regulating DNA damage repair due to radiation," says Afshin Beheshti, PhD, an adjunct assistant professor in the department of medicine at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey, who is also affiliated with the NASA Ames Research Center and Wyle Labs.

As principal investigator on a newly granted BRASH 1801 project, Beheshti has set out to use miRNAs as biomarkers for space radiation damage and as therapeutic agents for mitigating the damage.

"We hypothesize that circulating miRNA signatures are driving microvascular disease and muscle degeneration associated with accelerating aging and will be enhanced by exposure to the space environment (radiation and microgravity)," Beheshti explains. "We will investigate this hypothesis, both in vivo and in vitro, and test novel antagonist therapies to these miRNA signatures as countermeasures to reduce space radiation-induced health risks."

One key component to the research plan will be the Brookhaven National Laboratory on Long Island, where NASA has a set-up that can expose animals, tissues, and cells to various ions of various sizes and combinations in order to simulate the deep space radiation mix.

Beheshti's strategy takes advantage of the fact that miRNAs, being so small, are quite stable and thus can float freely, or can be packaged in exosomes, blood, or any other bodily fluid. Thus, miRNAs can act as novel and minimally invasive biomarkers. At the same time, because each RNA base has a corresponding base with which it can bind, special miRNAs can be designed to bind with the radiation damage-associated miRNAs that function as biomarkers.

If the approach proves effective, it may facilitate not only a new Space Age on par with the imaginative world of Star Trek, but also a greatly improved capability to protect patients undergoing radiation therapy and populations in settings of radiation accidents on Earth.

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