admin Mice treated aboard the International Space Station showed significantly less bone loss.
Bone loss caused by microgravity has long been a serious problem for long-duration space missions. The reduced mechanical stress of microgravity leads to bone loss twelve times faster than on Earth. The risk of bone fractures during long-duration space flight and later in life may increase for astronauts in low Earth orbit due to bone loss, which can last up to 1.5 months.
For crew members spending up to six months in microgravity, current techniques to control bone loss rely on exercise-induced mechanical loading to promote bone growth. However, they are far from ideal.Exercise can harm some diseases and does not always prevent bone loss. This also consumes significant crew time.
A new study led by Dr. Chia Soo, vice president for research in the Division of Plastic and Reconstructive Surgery and professor in the Departments of Surgery and Orthopedics at the David Geffen School of Medicine at the University of California, Los Angeles, revealed that a compound existed in mice aboard the International Space Station (ISS), which was artificially administered, largely prevented the bone loss associated with being in space. The study highlights a promising therapy for alleviating the extreme bone loss caused by long-term space travel and musculoskeletal degeneration on Earth.
The researchers first examined whether systemic administration of a NELL-1-like molecule (NELL-1) could reduce bone loss caused by microgravity. NEL-1 is crucial for bone development and maintenance of bone density.
The team must reduce the number of injections to systematically bring NELL-1 to the ISS. Increasing the half-life of NELL-1 from 5.5 to 15.Ben Wu, DDS, Ph.D., and Yulong Zhang, Ph.D., from the Forsyth Institute, increased the drug’s therapeutic potential within 5 hours without loss of bioactivity. They also bioconjugated neutral bisphosphonate (BP) to produce a “smart” molecule BP-NELL-PEG that more precisely targets bone tissue without the typical negative effects of BP.
They then evaluated the modified molecule to determine the effectiveness and safety of BP-NELL-PEG on Earth. They found that BP-NELL-PEG has excellent specificity for bone tissue without causing significant side effects.
Scientists worked closely with the Center for Advancing Science in Space (CASIS) and the National Aeronautics and Space Administration (NASA) Ames to make extensive preparations for the SpaceX CRS-11 mission to the International Space Station (ISS), where astronaut Peggy research led by Dr. Whitson and Mr. S. Jack D. Fisher. The remaining mice were returned to Earth 4.5 weeks after the introduction of the first Live Animal Returning (“LAR”) mouse in US history. Instead, half of the mice on the ISS were exposed to microgravity (“TER flight”) for an extended period of nine weeks to simulate the difficulties associated with long space travel.
TERM and LAR flight groups were treated with control BP-NELL-PEG or phosphate-buffered saline (PBS). An equivalent cohort of mice remained at the space center. Kennedy and similarly treated with BP-NELL-PEG or PBS to serve as normal terrestrial (“terrestrial”) gravity controls.
After administration of BP-NELL-PEG, ground and flight mice showed significantly greater bone growth.In orbit and on Earth, the treated mice showed no apparent adverse health effects.
Lead corresponding author Chia Soo said, “Our findings hold tremendous promise for the future of space exploration, particularly for missions involving extended stays in microgravity.“
Co-co-principal investigator Kang Ting said, “If human studies bear this out, BP-NELL-PEG could be a promising tool to combat bone loss and musculoskeletal deterioration, especially when conventional resistance training is not feasible due to injuries or other incapacitating factors.”
Co-co-principal investigator Ben Wu said, “This bioengineering strategy can also have important benefits on Earth, offering a potential therapy for patients suffering from extreme osteoporosis and other bone-related conditions.”
Journal Reference:
Ha, P., Kwak, J.H., Zhang, Y. et al. Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice. npj Microgravity 9, 75 (2023). DOI: 10.1038/s41526-023-00319-7
