Press Release

Amgen and NASA Team Up to Tap Weightless Environment of Space as Lab to Test Osteoporosis Treatment

By SpaceRef Editor

November 27, 2001

Filed under Lunar Resources Company, Space Physiology and Medicine, US

Half the women in America over the age of 50 will
eventually suffer fractures stemming from bone loss (osteoporosis),
and more than 30 million women will develop significant bone loss and
the resulting increased risk of serious bone fractures. Now, Amgen,
the world’s largest biotechnology company, and NASA (the National
Aeronautics and Space Administration) are teaming up to use the bone
loss experienced in space travel as a “laboratory” in which to
simulate accelerated osteoporosis. This collaborative study will
evaluate the ability of the Amgen investigational protein OPG
(osteoprotegerin – ahs-tee-oh-pro-teh-JEH’-rihn) to prevent bone loss
caused by a lack of weightbearing, a common problem for bedridden
seniors.

The experiment will be conducted on the space shuttle Endeavor
(STS-108), scheduled to be launched at the Kennedy Space Center on
November 29. It is being coordinated with the assistance of BioServe
Space Technologies, a non-profit, NASA-sponsored Commercial Space
Center (CSC) located at the University of Colorado and at Kansas State
University.

Osteoporosis has been considered by some to be a biological
consequence of aging. However, normal weightbearing and exercise are
important contributors to skeletal health. Like long-term bed rest,
space flight prevents the normal mechanical loading of bone. The
effects of gravity are reduced up to 1 million-fold during orbital
space flight. The degradation of bone is accelerated in space, leading
to losses of 0.5 percent to 2 percent of bone density per month.
Previous missions have documented decreases in bone density of 4
percent to 13 percent. This rate of bone loss has significant negative
implications for long-term manned space flight, and could limit the
duration of stays on the Space Station. Upon return to earth, bone
density in astronauts appears to recover slowly and perhaps
incompletely.

Just before the launch of mission STS-108, laboratory mice bred
specifically for laboratory testing will receive either OPG or
placebo. After these mice orbit in Endeavor for its planned 10-day
flight, the density of their bones will be measured to determine
whether OPG prevented microgravity-related bone loss.

“OPG appears to prevent bone loss in a variety of diseases,
including cancer, and we anticipate that a drug based on this molecule
will be effective in preserving bone mass in microgravity – whether
that applies to 50 astronauts or millions of bedridden senior
citizens,” said Paul Kostenuik, Ph.D., research scientist in Amgen’s
Metabolic Disorders group. “The prolonged therapeutic effect of a
single treatment allows for infrequent dosing, which may simplify
administration for astronauts and for osteoporosis patients.”

On a later mission (STS-107), and possibly on an early Space
Station opportunity, the level of existing OPG of the astronauts will
be compared before and after the mission to determine whether the
levels of this naturally occurring regulator of bone destruction are
influenced by microgravity.

Microgravity-induced bone loss is a significant barrier for
long-term space flight, and current drugs that treat osteoporosis are
not appropriate countermeasures for most astronauts. Use of the female
hormone estrogen is not possible for male astronauts. Gravity
facilitates the passage of tablet drugs into the stomach, where they
are absorbed into the blood stream. In a microgravity environment,
pills tend to remain in the esophagus where they are poorly absorbed.

Amgen discovered OPG in the mid 1990s as part of its genomics drug
discovery work and has been evaluating its safety and efficacy in
treating osteoporosis and the spread of cancer to the bones. OPG is a
naturally occurring secreted protein produced by most mammals,
including man. An injected protein, OPG helps regulate bone growth,
destruction and density by inhibiting formation of osteoclasts;
osteoclasts form from white blood cells and are responsible for
removing old bone from the bone surface. The old bone is replaced with
new bone by osteoblasts which come from the surrounding marrow. Higher
than normal levels of OPG are associated with significant increases in
bone density and bone strength.

In studies published in the peer-reviewed journal Genes and
Development, preclinical models lacking OPG displayed early onset of
osteoporosis. In this same study, OPG-deficient mice also exhibited
medial calcification of the aorta and renal arteries, suggesting that
regulation of OPG, its signaling pathway or its antagonist(s) may play
a role in the long-observed association between osteoporosis and
vascular calcification. (GENES & DEVELOPMENT, 12:1260-1268, 1998).

Amgen’s OPG development program is evaluating the injected
protein’s ability to safely and effectively treat osteoporosis and
cancer metastasis to bone.

Osteoporosis is a significant health threat for as many as 75
million people worldwide. About 80 percent of diagnosed patients are
women, but physicians are increasingly recognizing the importance of
treating men as well. Osteoporosis is characterized by low bone mass
leading to fragile bones and increased susceptibility to fractures.

Amgen is a global biotechnology company that discovers, develops,
manufactures and markets important human therapeutics based on
advances in cellular and molecular biology.

BioServe, housed in CU-Boulder’s aerospace engineering sciences
department, performed preliminary research with OPG on ground-based
simulations of space flight osteoporosis. “We also acted as the
intermediary between Amgen and NASA to obtain this flight opportunity
and others in the future,” said Ted Bateman, a BioServe biomedical
engineer who spearheaded the CU-Boulder portion of the project.

Established in October 1987, BioServe’s mission is to develop new
or improved products through space life science research in
partnership with industry, academia and government. BioServe’s NASA
charter directs the Center to foster commercial interest in the space
program.

An electronic version of this news release may be accessed via our
web site at www.amgen.com. Visit the Corporate Center and click on
Amgen News. Journalists and media representatives may sign up to
receive all news releases electronically at time of announcement by
filling out a short form in the Amgen News section of the web site.

Fact Sheet – The OPG Experiment on NASA’s Endeavor

Mission Name: Commercial Biomedical Testing Module Experiment

Shuttle Name: Endeavor, STS-108

Scheduled launch: 8:05 p.m. EST, November 29, 2001

Experiment location: Space Shuttle Endeavor middeck

Mission duration: 10-11 days

Principal Investigators:

Dr. Paul Kostenuik

Amgen

Thousand Oaks, California

Dr. Ted Bateman

BioServe Space Technologies, University of Colorado

Boulder, Colorado

Key Scientific facts

Effects of gravity are 1 million-fold decreased in space
Astronauts can lose 4 percent – 13 percent of bone in space. Bone
mass takes months to recover and may never fully return to
baseline
50 percent of women 50+ will suffer osteoporosis-induced fractures
More than 30 million people will develop osteoporosis and risk of
fractures

OPG (osteoprotegerin)

Protein produced by and found in humans
Discovered in the mid 1990s by Amgen scientists as part of Amgen’s
internal genomics drug discovery work
One of only a few genomics-based drugs in human trials
Helps regulate bone growth, destruction and density by inhibiting
formation of osteoclasts; osteoclasts form from white blood cells
and are responsible for removing old bone from the bone surface.
The old bone is replaced with new bone by osteoblasts which come
from the surrounding marrow
In studies published in the peer-reviewed journal Genes and
Development, preclinical models lacking OPG displayed early onset
of osteoporosis. In this same study, OPG-deficient mice also
exhibited medial calcification of the aorta and renal arteries,
suggesting that regulation of OPG, its signaling pathway or its
antagonist(s) may play a role in the long-observed association
between osteoporosis and vascular calcification. (GENES &
DEVELOPMENT, 12:1260-1268, 1998).
Amgen’s OPG clinical development program is also investigating the
protein’s ability to treat cancer metastasis to bone.

Experiment Hypothesis

Like long-term bedrest, spaceflight in a microgravity environment
eliminates the mechanical loading of bone(a) – this can
significantly increase the risk of osteoporosis
Microgravity during spaceflight actually represents an
experimental “model” for accelerated osteoporosis
The experiment will evaluate the ability of OPG to prevent bone
loss caused by lack of loading of the bone by treating 12
purpose-bred laboratory mice with a single pre-launch injection of
OPG, treating another 12 purpose-bred laboratory mice with placebo
and comparing the density of their bones upon their return

(a) Loading of bone is achieved through weight bearing exercises which
are absent during bed rest or space flight.