Systemic Therapy of NELL-1 for Osteoporosis (Rodent Research-5 (RR-5)) - 06.28.17

Overview | Description | Applications | Operations | Results | Publications | Imagery

ISS Science for Everyone

Science Objectives for Everyone
People and animals staying in space for extended durations experience bone density loss, or osteoporosis, and current countermeasures include exercise designed to prevent it from getting worse. But in space and on Earth, therapies for osteoporosis cannot restore bone that is already lost. The Systemic Therapy of NELL-1 for Osteoporosis (Rodent Research-5 [RR-5]) investigation tests a new drug that can both rebuild bone and block further bone loss, improving health for crew members in orbit and people on Earth.
Science Results for Everyone
Information Pending

The following content was provided by Chia Soo, M.D., F.A.C.S., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: Rodent Research-5

Principal Investigator(s)
Chia Soo, M.D., F.A.C.S., UCLA, School of Medicine, Los Angeles, CA, United States

Co-Investigator(s)/Collaborator(s)
Benjamin Wu, D.D.S., Ph.D., UCLA, School of Engineering, Los Angeles, CA, United States
Kang Ting, D.M.D., D.Med.Sc, UCLA, School of Dentistry, Los Angeles, CA, United States
Jin Hee Kwak, D.D.S., M.S., UCLA, School of Dentistry, Los Angeles, CA, United States
Louis S. Stodieck, Ph.D., University of Colorado, BioServe Space Technologies, Boulder, CO, United States

Developer(s)
BioServe Space Technologies, University of Colorado, Boulder, CO, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Earth Benefits, Scientific Discovery

ISS Expedition Duration
September 2016 - September 2017; September 2017 - February 2018

Expeditions Assigned
49/50,51/52,53/54

Previous Missions
The RR-1, RR-2, RR-3, and RR-4 missions validate all the hardware and procedures that are done on this mission.

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Experiment Description

Research Overview

  • Spaceflight has significant and rapid effects on the musculoskeletal system; therefore, it is important to investigate targeted therapies that could ameliorate some of the detrimental effects of spaceflight. The drug being studied in Systemic Therapy of NELL-1 for Osteoporosis (Rodent Research-5 [RR-5]) is a potential strategy to slow and/or reverse bone loss during spaceflight.
  • The drug is injected into mice every two weeks while they live in a zero-G environment on the International Space Station (ISS). Some mice return to earth to accomplish an additional research goal of determining if the drug improves how quickly animals recover and re-adapt to living on earth after being in space.
  • The impact of this research is to evaluate a new strategy to mitigate one of the negative effects of living in space (bone degradation). Additionally, this research may have applications in improving ground-based ailments related to bone loss such as extended bed rest or osteoporosis. The therapeutics developed as a result will potentially benefit millions of patients worldwide.

Description

The Center for the Advancement of Science in Space (CASIS) has formed a partnership with the University of California at Los Angeles (UCLA) to evaluate bone atrophy under microgravity conditions and to evaluate a novel therapeutic to mitigate bone loss.
 
Exposure to the spaceflight environment results in significant and rapid effects on the skeletal system, similar to what occurs in certain bone wasting diseases, as well as aging, on earth. Studying accelerated bone loss in space in collaboration with academic partners could provide insight into disease mechanisms, confirm potential new drug targets and enable the preclinical evaluation of a candidate therapeutic targeted to such disease. If this research is successful, it could lead to new treatments for bone loss associated with immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury and jaw resorption after tooth loss. Results of the Systemic Therapy of NELL-1 for Osteoporosis (Rodent Research-5 [RR-5]) investigation are expected to increase our understanding of ground-based diseases, disorders and injuries affecting millions of people globally and aid in the development of new therapeutics and strategies to treat such conditions.
 
Forty (40) mice (female, BALB/c mice between 30-40 weeks of age (32 week old mice preferred) are launched in two Transporters (20 mice per Transporter), transferred to Rodent Habitats onboard the ISS. Half of the mice are maintained in microgravity for approximately L+32 days (N=20, Live Animal Return [LAR]) and half for approximately L+9 weeks (N=20, ISS Terminal [IT]). All mice (N=40) initially undergo treatment with either control (vehicle only, and bone marker; N=20) or experimental (NELL1, and bone marker; N=20). Injections of vehicle and NELL1 are subcutaneous (s.c.), whereas injections used to administer the bone marker are intraperitoneal (i.p.). The mice are injected approximately L+1 week and at two-week (± 1 day) intervals (i.e., at approximately L+3 weeks). Dual-energy X-ray Analysis (DXA) scan are at approximately L+1, +5, and +9 weeks. All animals are anesthetized via intraperitoneal injection (i.p.) injection of ketamine/xylazine and recovered. After all forty (40) mice on orbit receive two treatments; ten (10) control mice and ten (10) experimental mice are randomly selected for LAR. The twenty (20) LAR mice, at approximately L+32 days (just prior to Dragon unberth), are transferred to a Dragon and transported live back to Earth.
 
The remaining (10) control mice and ten (10) experimental mice aboard the ISS (N=20, ISS Terminal [IT]) undergo two additional treatments at the same two-week (± 1day) intervals (i.e., at approximately L+5 weeks and approximately L+7 weeks). At approximately L+9 weeks, the IT mice are anesthetized and DXA scanned. Blood samples are obtained by cardiac puncture through closed chest, and the animals are then euthanized by exsanguination and cervical dislocation. The collected whole blood is separated by centrifugation, and the tubes then frozen and stored at -80˚C or colder. Samples are wrapped in aluminum foil and placed in storage at -80˚C or colder until return.
 
Ground controls are treated the same as flight animals but the ground procedures are offset from the flight schedule by 3 days.

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Applications

Space Applications
Spaceflight quickly causes major changes to the musculoskeletal system, including muscle weakness, bone weakness and bone density loss. Crew members on current missions exercise in an effort to maintain bone health, but new drugs will be necessary for crews traveling to distant destinations over a long period of time. This investigation injects a new drug based on a type of protein. Mice living on the ISS are injected with the drug every two weeks for the duration of their stay. Some of the mice will return to Earth to live in normal Earth conditions, so researchers can study whether the drug improves how quickly they recover. Results from this investigation improve efforts to mitigate bone loss, one of the key health problems related to living in space.

Earth Applications
Exposure to the microgravity conditions of space cause a rapid change in bone health, similar to what happens in certain bone-wasting diseases, during extended bed rest, and during the normal aging process. This investigation studies a drug that could prevent or even reverse accelerated bone loss in space. Results from this investigation may lead to new drugs for treating bone density loss in millions of people on Earth.

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Operations

Operational Requirements and Protocols

For this flight, 40 mice are flown in support of the research investigation aims. The ISS Crew transfers the Habitat from the SpaceX vehicle over to the ISS and installs it in the EXPRESS rack. The crew then moves the Transporter and Animal Access Unit to the ISS and performs animal transfer operations. Once the mice are housed in the Habitats, daily health checks will be performed via video that is recorded and downlinked to ground personnel.
 
Starting at approximately 1 week on orbit and every 2 weeks thereafter, mice receive either NELL-1 or control injections. Mice are transferred into the Microgravity Sciences Glovebox (MSG) five at a time to receive injections. They also receive an injection of a bone label at the same time.
 
At approximately 4 weeks into the mission, half of the mice (20) are transferred into a fresh Transporter and integrated back into the SpaceX Dragon vehicle for return to Earth. These mice are recovered following splashdown and transferred to an animal care facility at UCLA. The mice are given a DXA scan to assess bone mineral density shortly after return.
 
The mice that remain on board the ISS are also given a DXA scan and then continue to be exposed to microgravity through 9 weeks of total time on orbit. They then undergo an additional DXA scan before being euthanized and preserved for return and post-flight analysis. The mice that were allowed to recover on the ground are also euthanized for detailed analysis and comparison.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites
Plastic Surgery News
The Daily Bruin
UCLA Newsroom
American Dental Association (ADA)
CASIS article
NASA
National Institutes of Health (NIH)

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Imagery