In 2014, the National Aeronautics and Space Administration (NASA) launched the Rodent Research Project to study mice in space with the goal to better understand the effects of spaceflight on the human body. Using mice in space has helped researchers discover numerous things about microgravity (very weak gravity) situations. These discoveries have led to improving astronauts living conditions and health while in space and have also helped improve the lives of humans on Earth as well. Rodent Research studies have led to improvement in vaccines and therapies as well as a better understanding of muscle loss, vision and sleep disorders, and gastrointestinal disorders – just to name a few.
From 2014 to 2019, there have been 12 Rodent Research Projects, each one with its own health related objective. On Earth after the age of 50, humans can suffer a .5% bone loss each year. In space, astronauts can lose up to 1.5% in just one month. In June 2017, Rodent Research-5 (also called RR-5 or SpaceX-11) began with the objective to study mice to better understand the effects of the spaceflight microgravity environment in relation to rapid bone loss. Researchers hoped to not only solve the issue of bone loss for astronauts, but for people on Earth suffering from osteoporosis as well.
Osteoporosis is a disease that causes a loss of density in the bones often leading to bone fractures. Studies have shown in America, 50% of women and 25% of men will suffer a bone injury due to osteoporosis in their lifetime. In 2017, over 200 million people worldwide were affected with osteoporosis. Though this disease is more common for the elderly, osteoporosis can also occur for those with low mobility due to an injury, malnutrition or an illness. This bone disease can also lead to many complications such as spinal compression fractures, kyphosis (Dowager’s hump), and even height loss.
The foundation for RR-5 goes back to 1996. While studying children with an overgrowth of bone in their skulls, craniofacial orthodontist Dr. Kang Ting came across the bone-forming protein called NELL-1 as the key factor to the excess bone build-up in his patients. If NELL-1 could cause an overgrowth of bone in the body, Dr. Ting wondered if it could be used to help those with weakened bone.
Dr. Ting and his research team at UCLA began to test NELL-1 injections in various mice models with low density bones. They discovered that NELL-1 had the capability to stimulate bone formation through the restoration ability of stem cells. The study also showed that NELL-1 minimized the work of osteoclasts cells which are cells that break down bone.
Unfortunately, the RR-5 scientists later discovered that NELL-1 did not circulate very long in the bloodstream which was necessary for the protein to begin bone formation. To solve this problem, Dr. Ting and his team would need to inject NELL-1 multiple times a day into their mice models. The researchers soon discovered a solution to this inconvenience. Through the method of PEGylation (slowing the rate of molecules degrading in the liver), NELL-1 could combine with bisphosphonate (an inactive bone-seeking molecule). They called this combination BP-NELL-PEG and with it the scientists only needed to inject the mice once every 14 days.
After 18 years of continual research and seeing success from the mice models, Dr. Ting and his team submitted a proposal in 2014 to test BP-NELL-PEG on the International Space Station National Lab (ISS) and was later awarded the Center for the Advancement of Science (CASIS) Grant which supported the start of the Rodent Research-5 project. Because of the microgravity environment in space, the bones of mice weaken at a much more rapid pace then they would on Earth – making space the perfect test setting for the effectiveness of BP-NELL-PEG in repairing and preventing bone loss. If successful, it could offer future treatment for those suffering from osteoporosis.
In June 2017, Rodent Research-5 began and 40 mice were launched in a capsule up to the ISS. The mice were kept for four weeks in a microgravity environment, and 20 mice on the mission were injected with BP-NELL-PEG. In July 2017, 20 of the mice returned to Earth for further research – 10 of them have been injected with BP-NELL-PEG. Upon first inspection, the scientists discovered the injected mice’s fur was shiny and in great condition indicating the mice were doing well.
In further review of the injected mice, the Rodent Research-5 team discovered they had a substantial amount of bone loss but that this loss was successfully treated and recovered by the BP-NELL-PEG injection. This treatment they hoped could then
translate to an injection therapy for humans- both the astronauts traveling to space and those on Earth dealing with osteoporosis.
Though this mission was successful, BP-NELL-PEG still has some time before being sent to clinical trials. In a June 2018 interview with UpWard magazine Dr. Ting said, “Although modification and use of NELL-1 as a therapy has come far since its discovery more than 20 years ago, there’s still a long journey ahead before this treatment approach can be applied to humans. But that’s what research is about—you have persistence and tenacity, and you never give up.”
The Rodent Research project is currently on it 12th mission with more missions soon to come. Over the past 5 years since its beginning, each mission has provided new understanding and answers to various illnesses that effect the health of the human body. Thanks to these space mice, scientists are even closer to a treatment to help the millions of people dealing with osteoporosis daily. Animal research once again is showing to improve the lives of those here on earth and astronauts living in space.
By Nelia Dashiell
*feature image via NASA*