Overview | Description | Applications | Operations | Results | Publications | Images

Experiment/Payload Overview

Brief Summary

Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is one in a series of investigations designed to determine if administering an experimental agent preflight reduces the loss of bone associated with space flight. Humans and animals have been observed to lose bone mass during the reduced gravity of space flight. The sclerostin antibody is designed to inhibit the action of "sclerostin", a protein that is a key negative regulator of bone formation, bone mass and bone strength.

Principal Investigator

Chris Paszty, Ph.D., Amgen, Inc., Thousand Oaks, CA

Hua Zhu (David) Ke, M.D., Amgen, Inc., Thousand Oaks, CA

Martyn Robinson, PhD., UCB in Brussels, Belgium

Virginia Ferguson, Ph.D., BioServe Space Technologies, University of Colorado - Boulder, Boulder, CO

Louis Stodieck, Ph.D., University of Colorado, BioServe Space Technologies, Boulder, CO

Ted A. Bateman, Ph.D., University of North Carolina, Chapel Hill, NC

Mary L. Bouxsein, Ph.D., Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA

Co-Investigator(s)/Collaborator(s)

Information Pending

Payload Developer

Ames Research Center, Moffett Field, CA
BioServe Space Technologies, Boulder, CO
Amgen, Thousand Oaks, CA

Sponsoring Space Agency

National Aeronautics and Space Administration (NASA)

Supporting Organization:

National Laboratory Office (NLO)

ISS Expedition Duration:

March 2011 - September 2011

Expeditions Assigned

|27/28|

Previous ISS Missions

A similar investigation, CBTM, flew round trip to the ISS on STS-108 during ISS Expedition 4. CBTM-2 flew round trip to the ISS on STS-118 during ISS Expedition 15. AEMs have flown on numerous space shuttle missions over the years.

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Experiment/Payload Description

Research Summary

• The loss of bone mass during space flight remains a significant problem for human space missions, especially long-duration space flights. Varieties of countermeasures have been tried, mostly based on exercise, but have not proven to be totally effective in reducing bone loss.



• Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is an investigation focusing on a novel experimental agent. The agent is an antibody against the protein, sclerostin, a protein that is known to inhibit bone formation. If the agent is effective in reducing or preventing bone loss in mice during the flight, then it will demonstrate the potential for pharmacologic inhibition of sclerostin to be further tested for use in astronauts and in patients under disuse conditions. A different sclerostin antibody than the one being used for this STS-135 mouse study is currently in clinical trials as a collaboration between Amgen Inc. and UCB.

Description

Commercial Biomedical Testing Module-3: Assessment of sclerostin antibody as a novel bone forming agent for prevention of spaceflight-induced skeletal fragility in mice (CBTM-3-Sclerostin Antibody) is part of a suite of investigations studying the ability of novel experimental agents to prevent disuse induced bone loss, and extend current knowledge about the effects of microgravity on the musculoskeletal system and the ability of a ground-based analog system (rodent hind limb suspension) to reproduce those effects in mice. The ultimate objective is to mitigate the risk for space-induced skeletal fragility associated with missions to low Earth orbit, and exploration destinations. If the sclerostin antibody proves successful in reducing space flight induced bone mass loss in mice, then it will demonstrate the potential for pharmacologic inhibition of sclerostin to be used in astronauts. Beyond the perils of microgravity, the findings may also provide novel insight into prevention and treatment of the skeletal fragility that can result from ?skeletal disuse? in such conditions as immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury, and reduced physical activity. Eight to ten mice are flown in each of three Animal Enclosure Modules (AEMs) (http://flighthardware-spacebiosciences.arc.nasa.gov/) located on the space shuttle middeck. Half of the mice are given a preflight injection of a novel experimental bone forming agent, an antibody designed to inhibit the activity of the protein ?sclerostin?. The remaining mice receive a placebo. Following the flight, a team of scientists, are studying various aspects of the structure, composition, strength, and cell and molecular nature of the bones from the flight and ground-based control mice. Bones from mice receiving the bone forming agent are compared to those receiving the placebo and are also compared to a ground control group, i.e., mice that were housed in AEM's on the ground during the flight.

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Applications

Space Applications

If the novel bone forming agent proves successful in mitigating bone mass loss in-flight, this would demonstrate the potential application of pharmacologic sclerostin inhibition as a countermeasure for use in long-duration human space flight missions.

Earth Applications

If the sclerostin antibody proves successful in reducing space flight induced bone mass loss, the results may point towards possible prevention and treatment of the bone loss that can result from ?skeletal disuse? in such conditions as immobilization, stroke, cerebral palsy, muscular dystrophy, spinal cord injury, and reduced physical activity.

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Operations

Operational Requirements

AEM's with eight to ten mice each are requested for a late load (Launch minus 72 to 24 hours) and to be removed postflight within four hours of landing. During flight the crew is requested to conduct a daily health check of the mice, i.e., a visual observation through the Lexan lid of the AEMs. Unusual appearances of the mice are to be reported as soon as possible.

Operational Protocols

For this study nine week old female C57BL/6 mice are launched on the space shuttle. Flight mice are treated once with a placebo vehicle or the bone forming agent approximately 24 hours before launch. Ground control mice are treated in the same manner but with a 48 hour offset. Ground control mice are housed under the same environmental conditions (temperature, light/dark cycle, humidity, oxygen levels and carbon dioxide levels) as the flight mice. All mice receive the same full access to food and water. Upon return to Earth, the AEMs are returned to the research team for analysis. Body weight is also measured preflight and postflight. Statistical comparisons will be made between the treated and control mice.

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Results/More Information

Information Pending

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Related Web Sites

Space Biosciences Division

BioServe

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Publications

Results Publications

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Ground Based Results Publications

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ISS Patent Publications

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ISS Spinoffs Publications

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Related Publications

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Images

NASA Image: S118E09327 - STS-118 Mission Specialist Tracy Caldwell and Pilot Charles Hobaugh observing the Animal Enclosure Modules (AEMs) in the Middeck of the Space Shuttle Endeavour.
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Animal Enclosure Modules (AEMs) from NASA Ames Research Center. Image courtesy of NASA.
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Information provided by the investigation team to the ISS Program Scientist's Office.
If updates are needed to the summary please contact JSC-ISS-Program-Science-Group.