Promising BP-NELL-PEG compound may protect astronauts from rapid bone loss in space

After an unprecedented live return of mice from the International Space Station (ISS), the results were nothing short of astonishing. Soo, a plastic surgeon and scientist at the University of California, Los Angeles (UCLA), along with her team, had been eagerly waiting for the return of half of their research mice who had spent four and a half weeks in space. Their mission: to study the effects of a novel compound called BP-NELL-PEG on bone density.

The mice had traveled back to Earth aboard a SpaceX capsule, splashing down in the Pacific Ocean before reaching the UCLA lab. The team had no idea what condition the mice would be in after their space adventure. To their immense relief and delight, the mice emerged from their capsule healthy and active.

Astronauts in space experience rapid bone loss, losing approximately 1% of their bone mass each month— 12 times the rate of bone loss on Earth. This accelerated loss poses a significant challenge for long-term spaceflight, and mitigating it is crucial for the health and safety of astronauts. The initial findings from the study, published in npj Microgravity, suggest that BP-NELL-PEG could be a game-changer.

The root cause of bone loss in space is microgravity. On Earth, gravity’s impact on bones triggers tissue repair and inhibits reabsorption. In microgravity, this process is reversed: reabsorption is stimulated, while repair activities decline. Without the constant loading of bones that occurs on Earth when we walk and move, astronauts’ bone mass dwindles rapidly.

The first TBone study revealed that astronauts had not fully regained their lost bone density even after a year of being in space. Furthermore, the bone that did regenerate had a different microstructure, which raised questions about its strength and resilience. This underscores the pressing need for solutions to prevent bone loss beyond the existing exercise routines and osteoporosis drugs currently used in space.

BP-NELL-PEG, the compound developed by UCLA and Forsyth researchers, is built around NELL-1, a molecule known for its role in bone development and regeneration. It activates pathways that enhance bone cell formation and inhibit reabsorption, making it an ideal candidate for protecting against bone loss in space.

To test its efficacy, a study involving 40 mice on the ISS and 40 ground control mice at the NASA Kennedy Space Center took place. Half of each group received BP-NELL-PEG treatment, while the others received a control solution. Regular bone density measurements and 3D bone structure imaging using microcomputed tomography were conducted throughout the study.

The results revealed that treated mice on the ISS showed a significant increase in bone density in the lumbar spine and tibia compared to untreated mice. Although both groups experienced some bone density loss in the femur, the treated mice fared better. MicroCT analysis revealed improvements in the trabeculae, the porous material that makes up bone, in the treated mice.

Importantly, the cells in the treated mice’s bones exhibited signs of growth, indicating that BP-NELL-PEG promotes bone turnover and supports overall bone formation. This contrasts with bisphosphonate drugs, which halt bone turnover and may compromise bone quality.

While these results are promising, it’s important to remember that this study was conducted on mice in a space environment. Nonetheless, it represents a significant step forward in addressing bone loss during long-duration spaceflights, especially as space agencies contemplate missions to Mars and beyond.

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