Promising Engineered Compound Demonstrates Potential for Mitigating Bone Loss in Space Environments

A study recently published in npj Microgravity has unveiled a groundbreaking discovery: an engineered compound administered to mice aboard the International Space Station (ISS) has effectively thwarted the bone loss typically associated with prolonged space travel.

Conducted by a collaborative team of experts hailing from the University of California at Los Angeles (UCLA) and the Forsyth Institute in Cambridge, Massachusetts, this study sheds light on a promising therapeutic approach to combat the extreme bone loss encountered during extended space missions and also addresses musculoskeletal degeneration concerns on Earth.

For years, the scientific community has been deeply concerned about the detrimental effects of microgravity on bone health during prolonged space voyages. The absence of mechanical loading in microgravity conditions leads to bone loss at a staggering rate, 12 times faster than what occurs on Earth. Astronauts in low Earth orbit can experience bone loss of up to 1% per month, putting their skeletal well-being at risk and increasing the likelihood of fractures during extended space journeys and in later life.

Currently, the primary strategy to counteract this bone loss involves exercise-induced mechanical loading to stimulate bone formation. However, this approach is far from perfect for crew members spending up to six months in microgravity. Exercise does not consistently prevent bone loss, consumes valuable crew time, and may be unsuitable for individuals with certain types of injuries.

Led by Dr. Chia Soo, Vice Chair for Research in the Division of Plastic and Reconstructive Surgery and a professor in the Departments of Surgery and Orthopaedic Surgery at UCLA David Geffen School of Medicine, this study aimed to investigate whether systemic administration of NELL-like molecule-1 (NELL-1) could mitigate microgravity-induced bone loss.

NELL-1, initially discovered by Dr. Kang Ting at the Forsyth Institute, plays a pivotal role in bone development and the maintenance of bone density. Professor Ting has spearheaded numerous studies demonstrating that local delivery of NELL-1 can regenerate musculoskeletal tissues, including bone and cartilage.

To facilitate the systemic delivery of NELL-1 aboard the ISS, the research team worked on minimizing the number of injections. Dr. Ben Wu and Dr. Yulong Zhang at the Forsyth Institute extended the molecule’s half-life from 5.5 hours to 15.5 hours without compromising its bioactivity. They also bioconjugated an inert bisphosphonate (BP) to create a “smart” BP-NELL-PEG molecule, which more precisely targets bone tissues without the common deleterious side effects associated with bisphosphonates.

The modified molecule underwent extensive evaluation by the teams led by Dr. Soo and Professor Ting to assess its efficacy and safety on Earth. Their findings revealed that BP-NELL-PEG exhibited superior specificity for bone tissue without any observable adverse effects.

To validate the practical viability of BP-NELL-PEG in real space conditions, the researchers collaborated with the Center for the Advancement of Science in Space (CASIS) and NASA Ames to prepare for the SpaceX CRS-11 mission to the ISS. Astronauts Peggy Whitson, Ph.D., and Jack D. Fisher, MS conducted the experiments.

During the mission, half of the ISS mice were exposed to microgravity for an extended nine-week period (referred to as the “TERM Flight”) to simulate the challenges of long-duration space travel. The remaining mice were returned to Earth at 4.5 weeks post-launch, marking the first-ever live animal return (“LAR Flight”) of mice in US history. Both groups, TERM and LAR Flight, received either BP-NELL-PEG or a phosphate buffered saline (PBS) control treatment. An equivalent cohort of mice remained at the Kennedy Space Center and underwent similar treatment with BP-NELL-PEG or PBS to serve as “Ground” controls under normal Earth gravity conditions.

Remarkably, both the Flight and Ground mice treated with BP-NELL-PEG exhibited a significant increase in bone formation. Importantly, these treated mice in space and on Earth displayed no apparent adverse health effects.

Lead corresponding author Chia Soo expressed optimism about the implications of these findings for the future of space exploration, particularly for missions requiring extended stays in microgravity. Co-co-principal investigator Kang Ting emphasized the potential of BP-NELL-PEG as a tool to combat bone loss and musculoskeletal deterioration, especially when conventional resistance training is unfeasible due to injuries or other incapacitating factors.

Additionally, co-co-principal investigator Ben Wu highlighted the broader potential of this bioengineering strategy, suggesting that it could offer a promising therapy for patients suffering from severe osteoporosis and other bone-related conditions on Earth.

Looking ahead, UCLA project scientist Dr. Pin Ha will oversee the analysis of the live animal return data, with hopes that it will provide insights into helping future astronauts recover from longer-duration space missions.

Source: University of California, Los Angeles

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