Recent research has highlighted the effectiveness of a specially engineered substance in preventing bone loss in mice during space travel. This breakthrough has significant implications for both astronauts embarking on long space missions and individuals on Earth dealing with osteoporosis. A study published in the Nature Partner Journal, npj Microgravity on September 18, demonstrates that administering the engineered substance to mice aboard the International Space Station (ISS) substantially mitigated bone loss typically associated with extended periods in space. The study was conducted by a multidisciplinary team of professors from the University of California, Los Angeles (UCLA), and the Forsyth Institute in Cambridge, Massachusetts, shedding light on a promising therapeutic approach to address severe bone loss during prolonged space travel and musculoskeletal degeneration on Earth.
**Impact of Microgravity on Bone Health**
Bone loss induced by microgravity has been a significant concern for extended space missions. The reduced mechanical stress due to microgravity causes bone loss at a rate 12 times faster than on Earth. Astronauts in low Earth orbit may experience bone loss up to 1% per month, posing a threat to their skeletal health and increasing the risk of fractures during prolonged spaceflights and later in life.
**Current Approaches and Their Limitations**
Presently, mitigating bone loss relies on exercise-induced mechanical loading to promote bone formation, but it is not ideal for crew members spending extended periods in microgravity. Exercise does not always effectively prevent bone loss, consumes valuable crew time, and may not be suitable for certain types of injuries.
The recent study explored whether administering a molecule known as NELL-like molecule-1 (NELL-1) systemically could reduce microgravity-induced bone loss. Led by Dr. Chia Soo, the vice chair for research in the Division of Plastic and Reconstructive Surgery at UCLA, the study showcased that NELL-1, originally discovered by Dr. Kang Ting at the Forsyth Institute, plays a crucial role in bone development and maintenance of bone density. Extensive research by Professor Ting’s team demonstrated that localized delivery of NELL-1 can regenerate musculoskeletal tissues, including bone and cartilage.
**Innovative Delivery Techniques**
Systemic administration of NELL-1 aboard the ISS required the team to minimize the number of injections. Dr. Ben Wu and Dr. Yulong Zhang at the Forsyth Institute enhanced the therapeutic potential of NELL-1 by prolonging its half-life from 5.5 to 15.5 hours without compromising its bioactivity. They bioconjugated an inert bisphosphonate (BP) to create a “smart” BP-NELL-PEG molecule that targets bone tissues more specifically without the common detrimental effects of BP.
This modified molecule was extensively evaluated by the teams led by Dr. Soo and Professor Ting to determine its efficacy and safety on Earth. The results demonstrated that BP-NELL-PEG exhibited superior specificity for bone tissue without causing any observable adverse effects.
**Results and Practical Implications**
To validate the practical application of BP-NELL-PEG in real space conditions, the researchers collaborated with the Center for the Advancement of Science in Space (CASIS) and the National Aeronautics and Space Administration (NASA) Ames to prepare for the SpaceX CRS-11 mission to the ISS. Astronauts Peggy Whitson, PhD, and Jack D. Fisher, MS conducted the studies. Half of the mice on the ISS were exposed to microgravity for a lengthy 9-week period to simulate the challenges of extended space travel, while the remaining mice were returned to Earth at 4.5 weeks post-launch, marking the first-ever live animal return in US history.
Both the flight and ground mice treated with BP-NELL-PEG exhibited a significant increase in bone formation. Treated mice in space and on Earth showed no apparent adverse health effects.
**Conclusions and Future Prospects**
Lead corresponding author Dr. Chia Soo expressed optimism about the findings and their potential impact on future space exploration, particularly for missions involving prolonged stays in microgravity. Co-co-principal investigator Dr. Kang Ting highlighted that 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 Dr. Ben Wu emphasized the potential of this bioengineering strategy for patients suffering from extreme osteoporosis and other bone-related conditions on Earth.
The next steps involve analyzing the live animal return data to gain insights into aiding future astronauts in recovering from longer-duration space missions, led by UCLA project scientist Dr. Pin Ha.
For more details, you can refer to the original publication titled “Bisphosphonate conjugation enhances the bone-specificity of NELL-1-based systemic therapy for spaceflight-induced bone loss in mice,” published on September 18, 2023, in npj Microgravity, DOI: 10.1038/s41526-023-00319-7. The research has received support from grants by CASIS and the National Institutes of Health, as well as additional funding and support from various institutions and foundations. Co-first authors Pin Ha, MD, DDS, MS, and Yulong Zhang, PhD, and associate professor Jin Hee Kwak, DDS, made significant contributions to this project.