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July 11th, 2017

What space-traveling mice could mean for people with osteoporosis

By Tiare Dunlap

Drs. Ben Wu, Chia Soo, Kang Ting and Jin Hee Kwak at Kennedy Space Center

Early in the morning of July 3, 2017, 20 intrepid mice returned to Earth from the International Space Station aboard SpaceX’s Dragon capsule, splashing down in the Pacific Ocean off Baja, California. This landing marked the completion of a 28-hour journey back to Earth – and the first time live rodents have returned to the U.S. from the International Space Station.

But that’s not the only achievement that may earn this group of rodents a place in history. The outcome of this mouse-based mission (a collaboration between UCLA, NASA and the Center for the Advancement of Science in Space) could potentially benefit the 200 million people worldwide living with osteoporosis. That’s because the mice are receiving an experimental drug that aims to prevent bone loss.

Space is the ultimate testing ground for therapies to prevent bone loss because the microgravity environment leads to significant and rapid bone loss similar to the effects of osteoporosis and other bone-wasting diseases. These effects are common among returning astronauts, who, despite an extensive exercise routine, can lose up to 1.5 percent of their bone mass for each month spent in space.

Illustration of mice adapting to their space habitat on board the International Space Station. (Courtesy of the Center for the Advancement of Science in Space)

The experimental drug, developed at UCLA and based on a bone-building protein called NELL-1, works by stimulating specialized stem cells to create bone-building cells that generate new bone tissue. NELL-1 also inhibits bone-resorbing cells from destroying existing bone and has shown promising results in pre-clinical studies. If it proves effective in future clinical trials, the drug could prevent bone density loss during spaceflight and open n­­ew opportunities for humans to explore further into our galaxy.

It’s not only space travelers who could stand to benefit from NELL-1. After the age of 50, even earthbound humans begin losing their bone mass at an average rate of about 0.5 percent per year and up to 2 to 3 percent per year for post-menopausal women. This means that whether you’re planning to be the first person to reach Mars or simply hoping to remain physically active as you age, NELL-1 could one day change your life. Here’s an introduction to the interdisciplinary UCLA team behind the research:

Dr. Kang Ting, chair of the section of orthodontics and the division of growth and development in the UCLA School of Dentistry

Dr. Kang Ting discovered the NELL-1 protein’s role in stimulating bone growth while he was studying a rare condition that causes babies’ skulls to fuse too early. While NELL-1’s effect in these cases was detrimental, Ting and his colleague Dr. Ben Wu realized the protein could have a positive effect on people with bone injury or loss of bone mass– a group that includes older adults, people with traumatic bone injury, such as injured military service members, and of course astronauts. From there, the two researchers convened a team that would spend more than 18 years studying NELL-1’s effect on bone density.

Ting is enthusiastic about the potential of the drug:

“If this drug proves effective, it could really enhance the health and lives of so many people. That’s the exciting part – this discovery could shift the paradigm for treating osteoporosis in the future.”

Dr. Ben Wu, chair of the division of advanced prosthodontics in the UCLA School of Dentistry and professor in the schools of engineering and medicine

In 2000, Dr. Ben Wu joined the UCLA faculty, connected with Ting and began working on translating his discovery into a therapy that could help patients experiencing bone loss.  As a professor of engineering, Wu focused on developing molecules that could act as delivery vehicles for a therapeutic version of NELL-1. After 10 years of research on regenerating bone in targeted areas, such as in cases like spinal fusion or small fracture, the pair began to question whether NELL-1 could help patients with osteoporosis. This brought a new challenge, Dr. Wu explained:

“We had figured out how to get NELL-1 to stick to the scaffold of a damaged area, but with osteoporosis we needed to make it stick to everywhere that bone exists in the body.”

At the conclusion of an experiment process that Wu calls “decorating the NELL-1,” the pair landed on a molecule that they could attach to NELL-1. The molecule acts like a homing device that helps NELL-1 seek out and binds to bone tissue.

NELL-1 units are prepared for the space mission

Dr. Chia Soo, vice chair for research in the division of plastic and reconstructive Surgery, and a member of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA

Principal investigator on the project, Dr. Chia Soo has designed and overseen studies of the NELL-1 drug from the beginning. Over the years, her role as research director for UCLA Operation Mend, a program that provides medical care for injured military service members, has provided her with a constant reminder of the need for NELL-1.

“One of the things we’re really focused on is how to get bone to grow better in patients who really need it,” said Soo. “Our patients who are injured during military service deserve better therapeutic options.”

Soo sees the space mission as a pivotal moment in the decades-long project:

“If NELL-1 is found to be successful in a microgravity environment, the chances of it being successful on earth would be significantly greater.”

Dr. Jin Hee Kwak, assistant professor of orthodontics in the UCLA School of Dentistry

Preparing to test the drug in space represented an exciting – and daunting – opportunity, and no one shouldered more responsibility for the complicated logistics of UCLA’s first animal study with NASA than project manager Dr. Jin Hee Kwak. Conducting animal research in space requires an unfathomable amount of preparation. Kwak spent two years coordinating with NASA and CASIS and running an average of 20 trials for every single aspect of the experiment – from developing a mechanism to keep the mice stationary during bone scans to finding the best surgical method to implant identity chips in the mice in order to prevent extrusion or migration of the chip over time.  Now that the mice have returned alive and well, Kwak is getting a break from the logistics and a chance to reflect:

“Seeing that rocket blast off made me realize the power of this country and of teamwork. Pulling this off took a lot of people and coordination and seeing everyone working together towards one single goal was amazing.”

For more information on UCLA’s first rodent space travelers and the bone-building potential of NELL-1 read the news story.

Tags: bone density, Bone mass, David Geffen School of Medicine, Dentistry, experimental drug trial, international space station, Menopause, nasa, News & Insights, osteoporosis, research, space, stem cells, UCLA Broad Stem Cell Research Center

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