New research demonstrates the efficacy of an engineered compound in preventing bone loss in space-traveling mice. This breakthrough could provide a solution for astronauts and osteoporosis patients here on Earth. A new study published today (September 18) in Nature partner journal npj Microgravity has found that giving an engineered compound to mice aboard the International Space Station (ISS) largely prevented spacetime-related bone loss.
The study, led by an interdisciplinary team of professors at the University of California, Los Angeles (UCLA) and the Forsyth Institute in Cambridge, Massachusetts, highlights a promising therapy to mitigate the extreme bone loss caused by long-term space travel and musculoskeletal degeneration on Earth.
Microgravity-induced bone loss has long been an important issue on long-duration space missions. The reduced mechanical load caused by microgravity causes bone loss at a rate 12 times higher than on Earth. Astronauts in low Earth orbit may experience bone loss rates of up to 1% per month, which would compromise astronauts' bone health and increase their risk of fractures during long-duration spaceflight and later in life.
Current strategies to mitigate bone loss rely on exercise-induced mechanical loading to promote bone formation, but this strategy is far from perfect for crews exposed to microgravity for up to six months. Exercise does not always prevent bone loss, takes up valuable time on the part of the occupants, and may be a contraindication for certain types of injuries.
The new study investigated whether systemic administration of NELL-like molecule-1 (NELL-1) could reduce microgravity-induced bone loss. The study was led by Chia Soo, MD, associate chair of the Department of Plastic Surgery and professor of surgery and orthopedic surgery at the David Geffen School of Medicine at UCLA. NELL-1, discovered by Kang Ting, MD, of the Forsyth Institute, is critical for bone development and bone density maintenance. Professor Ding has also led multiple studies showing that local administration of NELL-1 can regenerate musculoskeletal tissues such as bone and cartilage.
Systemic delivery of NELL-1 on the International Space Station required the research team to minimize the number of injections. Ben Wu, Ph.D., and Yulong Zhang, Ph.D., of the Forsyth Institute, enhanced the therapeutic potential of NELL-1 by extending the half-life of the NELL-1 molecule from 5.5 hours to 15.5 hours without losing biological activity, and created a "smart" BP-NELL-PEG molecule by bioconjugating an inert bisphosphonate (BP) that can more specifically target bone tissue without the common harmful effects of BP.
The Soo and Ting teams then conducted an extensive evaluation of the improved 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 obvious adverse effects.
In order to determine the practicality of BP-NELL-PEG under actual space conditions, the researchers worked with the Center for the Advancement of Space Science (CASIS) and the National Aeronautics and Space Administration (NASA) Ames Branch to make extensive preparations for the Space Half of the ISS mice were exposed to a microgravity environment ("TERM flight") for up to nine weeks to simulate the challenges of long-duration space travel, while the remaining mice were flown back to Earth 4.5 weeks after launch in the first live mouse return in U.S. history ("LAR flight"). Both the TERM group and the LAR flight group received treatment with BP-NELL-PEG or a phosphate-buffered saline (PBS) control group. An equal number of mice remain at the Kennedy Space Center as a normal Earth gravity ("ground") control group and are also treated with BP-NELL-PEG or PBS.
Bone formation was significantly increased in both flying and ground mice treated with BP-NELL-PEG. Mice treated in space and on Earth had no apparent adverse effects on their health.
"Our findings hold great promise for future space exploration, especially for missions involving long-term stays in microgravity environments," said lead corresponding author Chia Soo. "If human studies confirm this, BP-NELL-PEG will be an effective tool in the fight against bone loss and musculoskeletal degeneration, especially in situations where traditional resistance training is impossible due to injury or other disabling factors."
"This bioengineering strategy could have important benefits here on Earth as well, providing a potential therapy for patients suffering from extreme osteoporosis and other bone-related diseases," said co-principal investigator Ben Wu.
"Next step, UCLA project scientist Pin Ha, MD, PhD, MS, will oversee analysis of the live animal return data. We hope this will shed some light on how to help future astronauts recover from longer space missions."