At a Glance
- Results from an ISS National Lab-sponsored investigation testing a new therapeutic to treat bone loss were published in the journal Nature Microgravity.
- The investigation, led by researchers at UCLA and the Forsyth Institute, tested the therapeutic's ability to reduce microgravity-induced bone loss in mice on the space station.
- Results demonstrated that the drug, BP-NELL-PEG, successfully reduced bone loss in mice without causing major side effects.
- These findings indicate the drug could be a promising therapy to help mitigate bone loss in osteoporosis patients on Earth and astronauts on long-duration spaceflight missions.
Researchers from the University of California, Los Angeles (UCLA) and the Forsyth Institute in Cambridge recently published results in the journal Nature Microgravity detailing how a novel therapeutic tested in mice onboard the International Space Station (ISS) could help people on Earth affected by osteoporosis. The investigation, led by Chia Soo, a plastic and reconstructive surgeon at UCLA Health along with Kang Ting and Ben Wu from the Forsyth Institute, was sponsored by the ISS National Laboratory®.
As humans age, we naturally lose bone density, but in space, bone loss is accelerated. Studies show that in the absence of countermeasures, astronauts in low Earth orbit (LEO) lose as much as 1% of their bone mass each month, which could increase the risk of injury on long-duration space missions but also later in life once the astronaut has returned to Earth. Similarly, studies have also found that spaceflight induces accelerated bone loss in mice. This bone loss is attributed to low levels of gravity, which reduces the amount of mechanical loading (or impact needed to help bones grow) placed on bones. So, studying rodents in microgravity provides an accelerated model of bone loss that scientists can use to test new therapeutics that could be valuable for both astronauts in space and osteoporosis patients on Earth.
The newly published study reports that a drug developed by UCLA Health, called BP-NELL-PEG, successfully diminished microgravity-induced bone loss without causing any major side effects in the mice who received the drug while on the space station. The results also indicate that the treated mice showed increased bone density, while the untreated mice lost significant bone density.
According to Soo, most readily available therapeutics for osteoporosis only work to slow bone loss and are unable to assist in the formation of new bone. Additionally, the drugs tend to be accompanied by unpleasant side effects. However, BP-NELL-PEG could be a game-changing treatment option because data collected from the team’s research shows it can both slow bone loss and promote bone formation, all with no significant side effects.
“Our results indicate [BP-NELL-PEG] is a promising therapeutic to mitigate extreme bone loss from both long-duration microgravity exposure and musculoskeletal degeneration on Earth, especially when patients are incapacitated like in cases of fractures or stroke,” Soo said. “These findings hold tremendous promise for the future of space exploration, particularly for missions involving extended stays in microgravity.”
The Search for Helpful Proteins
When Kang Ting, co-author on the paper and currently a professor at the Forsyth Institute in Cambridge, Massachusetts, was the attending orthodontist at the UCLA cranial facial clinic, he spent his time examining children with cranial facial abnormalities. In particular, he focused on craniosynostosis—a birth defect that occurs when the bones in a baby’s head fuse together prematurely, signaling an overgrowth of bone.
As a result, Ting identified a protein called NELL-1 that was prevalent in patients with excessive bone growth that might help patients who are struggling with bone loss. Through subsequent research, Ting and his colleagues at UCLA determined that a lack of NELL-1 could lead to symptoms of osteoporosis as an individual aged.
According to Soo, the NELL-1 protein has been shown to boost the activity of cells that form bone tissue, while also inhibiting the cells that break down bone and jump-starting processes involved in bone repair. “NELL-1 was chosen because it is one of a few molecules that not only can minimize bone loss but also may be able to restore bone that is already lost,” she said.
To determine if it is possible to leverage the bone forming properties of NELL-1 to treat osteoporosis, Soo’s team proposed an experiment to send a group of mice to the space station and treat them with a therapeutic called BP-NELL-PEG. This therapeutic is a modified version of the NELL-1 protein, designed by Wu to be administered systemically, meaning that a quick injection under the skin could treat the whole body.
According to Soo, the microgravity environment of the space station was an ideal platform to test the effectiveness of the BP-NELL-PEG therapeutic, as microgravity induces bone loss similar to the aging process, but on a much quicker timescale.
To streamline the experiment, the team also had to modify the drug to remain active in the body longer, so that fewer injections would be needed. Soo said that the team also paired it with a bisphosphonate drug that helps BP-NELL-PEG target bone more easily.
Testing NELL-1 in Flight
The experiment, which launched on SpaceX’s 11th Commercial Resupply Services mission in 2017, involved two sets of mice: one group of 40 that were sent to the ISS and another group of 40 that were used as a ground control. According to Soo, half of the mice in both groups received BP-NELL-PEG and the other half received a saline solution. After nine weeks, the treated mice (both in space and on Earth) showed a significant increase in bone formation, the untreated ISS mice showed a decline, and the untreated Earth mice remained stable.
Soo noted that the experiment did have some limitations. For instance, the team couldn’t closely track the animals’ behavior, so factors like stress could not be taken into consideration. She also explained that it would be difficult to repeat multiple experiments or expand upon them because that would require sending additional experiments to space.
However, Soo did say that the team’s space-based research could help pave the way for more advanced osteoporosis therapies. Currently, there is a company developing NELL-1 for use as a therapeutic to help grow local bone in adults undergoing surgery for degenerative disc disease, which causes the discs of the spine to wear out over time.
Soo and her team are continuing to review data from their experiment, including data collected from the mice after they returned to Earth. Soo said that the team set out to determine if their therapeutic could reduce bone loss in microgravity, which it did. Next, they will try to use the data from the returned mice to uncover new insights into how astronauts might recover from long trips to space.
Read more about Chia Soo’s research in the Upward feature “Building Bones: Testing a New Osteoporosis Therapy With Mice in Microgravity.”