It seams problem is in drug-delivery at disease center!!??
Gene Linked To Breathing Disorders
CLEVELAND, Sept. 3, 1996 -- One of the miracles of life is a newborn's ability to begin breathing on its
own. Now scientists at Case Western Reserve University School of Medicine report a major advance in
understanding the postnatal development of normal breathing behavior, as well as how this process can
become fatally impaired. The researchers have shown that a naturally-occurring, hormone-like molecule,
called Brain-Derived Neurotrophic Factor (BDNF), is required for the development of normal breathing
after birth.
Using genetically engineered mice, the scientists found that animals lacking BDNF were missing a specific
group of nerve cells critical for the control of respiration and displayed severely abnormal breathing
responses to various environmental conditions. The breathing abnormalities were associated in particular
with an inability to sense changes in blood oxygen levels. BDNF-deficient mice die within two to three
weeks after birth, and it now appears likely that the animals' premature death is linked to their breathing
difficulties.
According to David M. Katz, Ph.D., associate professor of neurosciences and leader of the research
team, "The findings are significant because they establish a link between a gene required for nervous
system development and a specific disorder of breathing in mice. Particularly intriguing are possible
relationships between the mechanisms underlying abnormal breathing in the mutant mice and disorders
such as Sudden Infant Death Syndrome, sleep apnea, and Congenital Chronic Hypoventilation Syndrome
(Ondine's Curse) in human patients."
According to James P. Kiley, Ph.D., director of the Airway Biology and Disease Program of the National
Heart, Lung, and Blood Institute, "Identifying genetic factors responsible for specific respiratory defects is
an important area of research since such studies contribute significantly to fundamental knowledge of
genetic based defects and respiratory control mechanisms in health and
disease."
An infant's inability to sense or respond to dangerously low oxygen or high carbon dioxide levels may play
a role in Sudden Infant Death Syndrome (SIDS), one of the commonest forms of death in apparently
healthy children between two and six months of age. In premature infants, impaired responses to low
oxygen levels may predispose them to prolonged periods of respiratory arrest, termed "apnea of
prematurity," which can in turn derange normal development.
Even more common is adult sleep apnea, a condition affecting approximately 12 million Americans, in
which the ability to "sense" abnormal breathing is thought to be important in arousing a person from
potentially life-threatening episodes of airway obstruction. Recent studies in humans, carried out by Susan
Redline, M.D. and her colleagues, also at Case Western Reserve University School of Medicine, have
demonstrated a familial association between SIDS, sleep apnea and impaired responses to low oxygen,
raising the possibility that these conditions share a common underlying mechanism.
"Although our results are just a first step, it is possible to imagine one day using a molecule such as BDNF
to augment maturation or functioning of the oxygen sensing system and thereby treat disorders of breathing
in human patients," said Dr. Katz.
The research, which is supported by the National Heart, Lung and Blood Institute of the National
Institutes of Health and the Francis Families Foundation, was carried out by a post-doctoral fellow in Dr.
Katz's laboratory, Dr. Jeffery Erickson, in collaboration with scientists at the Centre Nationale des
Recherches Scientifiques (Gif-sur-Yvette, France), Regeneron Pharmaceuticals, Inc. (Tarrytown, NY)
and Bristol-Myers Squibb (Princeton, NJ). The mice carrying the BDNF gene deletion were produced at
Regeneron by a research team headed by George D. Yancopoulos, M.D., Ph.D., Regeneron's vice
president, Discovery. Regeneron is collaborating with Amgen Inc. and Sumitomo Pharmaceuticals
Company, Ltd. on BDNF development. Dr. Yancopoulos commented that "the work of Dr. Katz and his
colleagues may lead to new treatment possibilities for patients with breathing disorders." The study
appears in the September 1, 1996 issue of the Journal of Neuroscience, the official journal of the Society
for Neuroscience.
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