FY2003 President's Budget Request for the NIDCD
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Fiscal Year 2003 President's Budget Request
for the National Institute on Deafness and Other
Communication Disorders
Statement by
Dr. James F. Battey, Jr.
Director, National Institute on
Deafness and Other Communication Disorders
I am pleased to present the President's budget request for the National
Institute on Deafness and Other Communication Disorders (NIDCD) for FY
2003, a sum of $371,951,000, which reflects an increase of $28,880,000
over the comparable FY 2002 appropriation. The NIH budget request includes
the performance information required by the Government Performance and
Results Act (GPRA) of 1993. Prominent in the performance data is NIH's
second annual performance report which compared our FY 2001 results to
the goals in our FY 2001 performance plan.
Disorders of hearing, balance, smell, taste, voice, speech, and language
exact a significant economic, social, and personal cost for many individuals.
The NIDCD supports and conducts research and research training in the
normal processes and the disorders of human communication that affect
many millions of Americans. Human communication research now has more
potential for productive exploration than at any time in history. With
substantive investigations conducted over the past decades and the advent
of exciting new research tools, the NIDCD is pursuing a more complete
understanding of the scientific mechanisms underlying normal communication
and the etiology of human communication disorders. Results of this research
investment will foster the development of more precise diagnostic techniques,
novel intervention and prevention strategies, and more effective treatment
methods.
Excessive noise has long been recognized as an occupational hazard among
adults, and hearing conservation programs have been implemented in the
workplace. However, the resiliency of a child's auditory system following
noise exposure needs further research. Chronic exposure to loud music,
fireworks, lawn mowers, or toys can accumulate over a lifetime to gradually
produce irreversible damage to the sensory cells of the inner ear. The
results of a recent survey conducted by the Centers for Disease Control
and Prevention revealed that approximately 5.2 million American youths
have some degree of hearing loss due to exposure to noise at hazardous
levels.
Identification of Genes Causing Deafness
Hearing loss occurs with a frequency of about 1 in 1,000 newborns and
is also a prevalent, but not necessarily inevitable, feature of the aging
process. Causes of hearing loss in children and the elderly include viral
and bacterial infections, loud noise, head trauma, drugs or other chemicals
that are toxic to the sensory cells of the inner ear, as well as mutations
in genes critical for normal auditory function and development. NIDCD
scientists are identifying the genes whose mutations result in hearing
loss. Recently, NIDCD Intramural scientists identified a gene located
on chromosome 10 that is involved in Usher syndrome type 1D (USH1D). Individuals
that inherit two copies of this mutated gene are born profoundly deaf,
have severe balance problems, and gradually lose their sight beginning
in adolescence. The scientists discovered that USH1D gene encodes a protein
called cadherin-23. Knowledge of the function of cadherin-23 in the inner
ear will provide new insight into cellular processes essential for normal
auditory function, which may ultimately guide the development of improved
diagnosis and treatment methods. NIDCD expects to support collaborations
between its Intramural scientists and those of the National Eye Institute
in these areas.
NIDCD scientists also identified a gene (DFNB29) located on chromosome
21 whose mutation caused recessively inherited hearing loss. This gene
encodes a protein, claudin-14, which is believed to help seal adjacent
cells together in the inner ear thus preventing the leakage of endolymph
fluid. The endolymph bathes the sound transduction cells and is essential
for conversion of the mechanical energy of sound into an electrical signal
that is sent to the brain. Studies are underway in a new mouse model to
advance our understanding of the function of claudin-14.
Discovery of Novel Deafness Genes and Genetic Characterization of
Hearing Impairment
NIDCD has developed a substantial research portfolio to study existing
mouse mutants as well as creating new mouse models to facilitate the discovery
and analysis of genes whose mutation causes hereditary hearing impairment
in humans. In a recent study utilizing the mouse mutant Waltzer, NIDCD
Intramural scientists showed that mutations in the human cadherin gene
family cause Usher Syndrome type 1D. This mouse model is a critical research
tool for determining the identification of the mechanisms by which cadherin
mutations cause this devastating deafness and blindness syndrome. In another
NIDCD-supported study, a mouse nuclear gene has now been shown to interact
with mutated genes in the mitochondria to significantly alter the severity
of age-related hearing loss. This model system should provide important
information regarding age-related hearing loss in humans, a relatively
common and debilitating health problem within the aging U.S. population.
These findings underscore the power of mouse genetics and the value of
mouse models of deafness for the identification and detailed molecular
characterization of human hearing impairment.
Scientists Identify Sweet Taste Receptor Gene
Understanding the molecular and cellular events that occur at the early
stages of taste perception at the level of the taste receptor cell provides
important insight into how we taste different sweet, bitter, salty, and
sour substances. A variety of distinct signaling pathways are activated
by the basic taste qualities of salty, sour (acid taste), sweet, and bitter.
Salty- and sour-tasting compounds activate ion channels that are located
at taste receptor cells clustered within taste buds of the tongue and
palate, while bitter and sweet compounds bind to G protein-coupled receptors.
Recently, four NIDCD-supported laboratories independently identified a
gene, T1R3, at the mouse Sac locus that encodes a sweet taste receptor
subunit. Differences in sweetener intake among inbred strains of mice
are partially determined by variation in genes at the saccharin preference
(Sac) locus. It was determined that the T1R3 receptor differs in
amino acid sequence in "sweet preferring" versus "sweet indifferent" mouse
strains. Both human and mouse T1R3 are G protein-coupled receptors, and
are selectively expressed in subsets of taste receptor cells that are
sensitive to sweet substances.
Abilities in Auditory Pitch Recognition Are Largely Inherited
Auditory pitch recognition is a complex process that allows us to determine
the pitch or tone of a sound. In this process, the ears receive the sound
signal and the brain interprets this signal to produce the pitch we perceive.
Individuals with problems in pitch recognition are sometimes referred
to as "tone deaf." Severe deficits in pitch recognition may be associated
with speech and language disorders. It was long known that tone deafness
can run in families. However, it was not known whether this disorder was
due to inherited genes or to a common environment shared by family members.
To answer this question, NIDCD Intramural scientists performed a large
study on twins. The results show that identical twins scored much more
alike than fraternal twins on a Distorted Tunes Test. The data revealed
that approximately 70-80% of an individual's score is due to their genes
and 20-30% due to other factors. The discovery that individual differences
in pitch recognition are mostly genetic opens up the possibility of using
genetic methods and information from the Human Genome Project to find
the genes essential for pitch recognition. Identifying such genes and
how they function will provide new insight into how the brain processes
sound.
How Basic Biology Translates into New Technology to Help the Hearing
Impaired
Over the past decade, NIDCD-supported scientists have been studying
the amazing auditory capability of Ormia ochracea, a tiny parasitic
fly with such acute directional hearing that it has inspired a new generation
of hearing aids and nanoscale listening devices. Ormia can detect
very small differences in sound-source position, a situation analogous
to humans trying to detect who is speaking in a crowded room. This accomplishment
is due to the unique anatomy of the eardrums of Ormia. The fly's
eardrums are connected internally by a cuticle-based bridge that functions
as a flexible lever. This unusual structure allows the membranes of the
eardrum to vibrate in response to sound in two distinct ways, with different
resonant frequencies. Trying to mimic the Ormia ear in silicon,
engineering groups so far have developed prototype "microphone eardrums"
that function "Ormia-like" as predicted but at ultrasonic frequencies.
Additional research will be needed to generate prototypes that detect
sound in the range of normal human hearing, that will be highly directional,
fit inside the ear canal, and be affordable. Other applications of the
Ormia-inspired silicon ear might include robotic listening devices.
These latest findings have led to collaborations between neurobiologists
and engineers to make a directional hearing aid that would be smaller and
simpler and cost less than currently available devices.
Although hearing aid technology has advanced rapidly over the last few
decades, the various hearing aids available still do not function well
in real world situations where sound from more than one source is present,
and they are not particularly effective in restoring the listener's ability
to cope with the problem of attending to a single speech source among
competing speech sources. NIDCD-supported scientists are actively engaged
in research to develop "intelligent" hearing aid systems that are capable
of selectively locating and characterizing a sound in a crowd.
Functional Brain Imaging as a Tool to Understand Cochlear Implant
Performance
The cochlear implant is the first clinically useful neural sensory prosthesis
to replace a human sense. It converts sound into electrical impulses on
an array of electrodes that is surgically inserted into the inner ear,
bypassing the inner ear hair cells and stimulating the auditory nerve
directly, restoring the perception of sound to persons who are totally,
or almost totally, deaf. This device has allowed adults who lost their
hearing to recover an ability to understand speech. Although speech perception
performance of adults has steadily increased with new advances in cochlear
implantation, wide performance variations exist among cochlear implant
recipients. Differences in structural and functional abnormalities of
the auditory system may play a role in this variability. However, little
is known about the reorganization of the auditory system following deafness,
or on the preservation or recovery of auditory function following cochlear
implantation. NIDCD-supported scientists have completed preliminary studies
examining functional brain imaging in individuals before and after cochlear
implantation. The data suggest that preoperative to postoperative changes
in the brain's responsiveness as measured by imaging are related to improvements
in speech perception scores. Also, despite relatively similar hearing
losses in each ear, significant differences in preoperative auditory cortex
activation were observed between ears, which may help guide selection
of the more appropriate ear for implantation.
Phase I Clinical Trial of an Otitis Media Vaccine Candidate
Otitis media (OM) is the most common reason for a sick child to be evaluated
by a physician, a public health burden estimated to cost approximately
$5 billion a year in the U.S. In addition to the cost savings, prevention
of OM is particularly important because repeated antibiotic treatment
of OM often results in the appearance of drug-resistant strains of bacteria
which can no longer be eradicated with first-line antibiotics. NIDCD Intramural
scientists have developed candidate vaccines that would protect infants
from OM caused by two major bacterial pathogens: nontypeable Haemophilus
influenzae and Moraxella catarrhalis. These two pathogens account
for two-thirds of OM cases in children, and there is no vaccine available
for prevention of the disease. Pre-clinical testing with such vaccines
from nontypeable H. influenzae demonstrated that the vaccines could
generate specific immunity against the bacteria and reduce bacterial colonization
in nose and throat, and reduce the incidence of OM in animal models. In an additional
clinical trial involving 40 normal human adult volunteers, one such vaccine
directed against H. influenzae proved to be both safe and effective,
eliciting a significant immune response against the bacteria. This candidate
vaccine will soon be tested in a second trial for safety and effectiveness
in children. For Moraxella catarrhalis, similar preclinical approaches
were taken, resulting in several candidate vaccines. Pre-clinical testing
in animal models with vaccines for Moraxella catarrhalis demonstrated
that the vaccines were safe and effective, eliciting a significant immune
response that inhibited bacterial growth.
Additional clinical trials are planned to test these candidate vaccines for safety and efficacy in humans.
Genetic Testing and the Clinical Management of Nonsyndromic Hereditary
Hearing Impairment
In the last decade, approximately 20 genes whose mutations result in
nonsyndromic hearing impairment have been identified and isolated. Mutations
in one of these genes, GJB2, accounts for about 25% of all autosomal recessive
nonsyndromic hereditary hearing impairment in American children. With
the identification of genes that contribute to hearing function, genetic
testing becomes technically possible but not necessarily suitable for
widespread clinical application at present. With the enactment of some
type of legislation that requires universal hearing screening for newborns
in 36 states, not only are infants with severe hearing impairment identified
much earlier in life but infants with lesser degrees of hearing impairment
are now also being identified. Many unresolved issues remain for clinicians
as they characterize auditory performance in a newborn who fails hearing
screening, design intervention strategies to optimize communicative success,
and ensure that a "medical home" exists for the infant with hearing impairment.
The advances in the genetics of hereditary hearing impairment and in the
early identification of hearing impairment have now converged. These advances
have led some to suggest genetic testing/evaluation for all infants who
are identified with a hearing loss at birth. In consideration of these
developments, the NIDCD and the National Human Genome Research Institute
are collaborating on an initiative to address the clinical relationship
between genetic and audiologic/otologic information, as well as to address
the clinical validity and utility of genetic testing in the diagnosis,
treatment, and management of nonsyndromic hereditary hearing impairment.
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