Download The Hearing Restoration Project

The Hearing
Restoration Project
A Groundbreaking Research Consortium
to Cure Hearing Loss and Tinnitus
A Cure for Hearing Loss and
Tinnitus is Coming!
A
cure for hearing loss and tinnitus is at hand. Hearing Health Foundation, the largest
non-profit funder of hearing research, is leading an international, multi-institution
research consortium called the Hearing Restoration Project (HRP) that will develop therapies
to cure these conditions within the next 10 years.
This means that for many living with hearing loss and tinnitus a cure is possible within
their lifetimes!
The promise of a real, biologic cure is focused on the inner ear hair cells that make hearing
possible. Most types of hearing loss are the result of damage to these hair cells, including
noise-induced hearing loss, age-related hearing loss and ototoxic hearing loss. Twenty-five
years ago, research funded by Hearing Health Foundation revealed something remarkable:
birds have the ability to re-grow damaged inner ear hair cells and spontaneously restore their
hearing. In humans, hearing loss is permanent once the hair cells are damaged.
The goal of the HRP is to develop a biologic cure by applying what we know about
chickens to people, and regenerating the hair cells in humans to permanently restore hearing.
To achieve a cure, we have assembled a consortium of 11 leading hearing loss research centers
and research teams:
Baylor College of Medicine
Harvard Medical School
Imperial College London
Oregon Health & Science University
Stanford University School of Medicine
Stowers Institute for Medical Research
University of Michigan
University of Southern California
University of Toronto
University of Washington
Washington University School of Medicine
Hearing Health Foundation is ideally positioned to lead this world-class consortium and
deliver on the goal of a cure. Since 1958, Hearing Health Foundation has led the way in
supporting the most cutting-edge research for the prevention, treatment and cure of hearing loss.
To support the Hearing Restoration Project, we will need to raise approximately $50 million
over the next ten years to fund the medical equipment, genomic testing, bioinformatics and
researchers needed to change the course of hearing loss forever. With funding for the HRP
coming exclusively from non-government sources, we now seek philanthropic gifts from our
supporters and from those who want to see a cure…..mothers, fathers, children, veterans,
professionals and people from every walk of life.
On behalf of Hearing Health Foundation, we thank you for your interest in our efforts
and hope that you will join us in finding a cure.
Sincerely,
Shari Eberts
Chairman
Hearing Health Foundation Board
2
Introduction
T
hroughout history every major medical breakthrough has been achieved from an
infusion of research dollars from individuals and institutions. From polio, to breast
cancer, to Alzheimer’s disease, great strides have been made when those affected come together
to support research. For those touched by hearing loss or tinnitus, there has never been a
better time to mobilize to treat and cure hearing loss.
For the first time, researchers are on track to develop a genuine, biologically-based cure
for most types of acquired hearing loss. We know that just as cochlear implants changed
the treatment options for those living with hearing loss, cell regeneration is the next wave of
game-changing hearing treatments.
With the top hearing research laboratories and researchers working together, sharing data,
and collaborating on their research through the Hearing Restoration Project, we will actually
be able to speed up the timeline for a cure from 50 years to just 10 years. This means that for
many living with hearing loss or tinnitus a cure is possible within their lifetimes!
Need: The Time is Now for All of Us Who Are Affected By Hearing Loss
As you read this, nearly 50 million Americans are living with some form of hearing loss that
is impacting their daily lives at home, at work, at play and at school. Even more astonishing is
that hearing loss is affecting people all across our society: 1 in 7 adults, 1 in 5 teenagers and
60% of our returning veterans from Iraq and Afghanistan have a hearing loss. And, by
2030, the total number of people living with hearing loss is expected to double.
Hearing loss affects people of every age and from every background: from newborn children,
to older Americans, to military personnel, to business professionals, to professionals in our
manufacturing and service sectors. And the causes of hearing loss are many: age-related,
genetics/family history of hearing loss, noise-induced, infections, trauma and toxic-induced
hearing loss.
Regardless of the cause, hearing loss has a profound impact on the lives of those who live
with it and on their loved ones. Frustration, fear, isolation and depression are common for
people living with a hearing loss.
Right now there are limited treatment options for hearing loss, including hearing aids,
assistive listening devices and cochlear implants. However, these are not effective for everyone
and the costs to a person and family are significant. Currently, there are no cures for
hearing loss or tinnitus.
Blindness separates
people from things;
deafness separates
people from people.
—Helen Keller
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A New Way of Doing Things
F
or too many years, biomedical research has been conducted in relative isolation: one
researcher or one institution working alone to tackle major health issues. Today, we
know that research progress is enhanced by the collaboration of scientists with diverse areas
of expertise. Simply put, no single laboratory or institution has sufficient breadth of expertise
and technology to solve all problems.
Furthermore, medical researchers in cell regeneration and hearing science face greater
competition for funding each year and from a decreasing pool of funds from the National
Institutes of Health (NIH) and other large medical research funders.
Hearing Health Foundation is tackling these issues of medical research funding and
progress by focusing our efforts on a collaborative, targeted and fully-funded approach:
the Hearing Restoration Project.
Hearing Health Foundation:
Since 1958, the Leading Non-Profit Supporting Research to End Hearing Loss
The mission of Hearing Health Foundation is to prevent and cure hearing loss through
groundbreaking research. We are America’s leading source of private funding for research into
the science of hearing and balance. Since 1958 we have awarded approximately 2,000 grants
totaling nearly $30 million through our Emerging Research Grants program.
Deafness Research Foundation (now called Hearing Health Foundation) was founded in
1958 because of the vision, strength and determination of one remarkable woman: the late
Collette Ramsey Baker.
Collette Ramsey Baker.
I want to see a cure
before I die. I’m so
excited for my children’s
future because of people
like you!
—Kille, mother of two kids with hearing loss
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After living with a substantial hearing loss for many years, at age 35 an early fenestration
operation restored Mrs. Ramsey Baker’s hearing. In gratitude, she wanted to donate money
to a national non-profit organization that was supporting hearing and balance research, but
no such organization existed at the time. That was when she decided to create a non-profit
that could support medical research to further hearing loss treatments, prevention and a cure.
Under her incredible leadership, we bestowed grants upon colleges and other research
institutions for research and improvement of hearing. Mrs. Ramsey Baker received letters
of commendation from many leaders, including Presidents Herbert Hoover and Dwight D.
Eisenhower, as well as Helen Keller and Cardinal Francis Spellman.
Since 1958, the organization has made incredible breakthroughs in research and care,
including the co-founding of the National Temporal Bone Banks Program, passing of the
Universal Newborn Hearing Screening legislation, contributing to the development of the
cochlear implant, and surgery for otosclerosis.
Hearing Restoration Project (HRP):
The REAL Promise of a Cure
H
earing Health Foundation has launched its most important research initiative ever:
the Hearing Restoration Project. Our goal is to deliver, for the first time, a genuine,
biologic cure for the millions of people living with hearing loss and tinnitus.
The project is based on the discovery funded by Hearing Health Foundation in 1987 that
birds spontaneously regenerate the hair cells necessary for hearing when those cells become
damaged; humans cannot. But recent discoveries in stem cell research and gene mapping may
make now the time to trigger hair cell regrowth in humans in the near future.
The Consortium Model
Through the Hearing Restoration Project, leading researchers have committed to our
consortium model – working together, fully sharing technologies, data, and credit – to
discover the secret of regenerating inner ear hair cells in humans. Their goal is nothing less
than a cure for hearing loss and tinnitus.
The HRP is collaborative rather than competitive, and relies on the strengths of our
researchers towards a common goal. The consortium members are experts within their own
right, and are working individually on different aspects of regeneration—including nerve
regeneration, stria development, and hair cell regeneration across multiple species—and then
pooling their resources and findings to help find a cure for hearing loss through collaborative
projects and data sharing.
If you really want to
cure hearing loss, hair
cell research is the
only game in town.
—Dr. Edwin Rubel, Department of
Otolaryngology, Graduate Program in
Neurobiology and Behavior, University of
Washington; Hearing Restoration Project
Consortium Member.
The Best and Brightest
The consortium is comprised of the best and brightest researchers in hearing science from
the following institutions:
Baylor College of Medicine
Harvard Medical School
Imperial College London
Oregon Health & Science University
Stanford University School of Medicine
Stowers Institute for Medical Research
University of Michigan
University of Southern California
University of Toronto
University of Washington
Washington University School of Medicine
Hair Cells, Explained
Hair cells are specialized sensory cells located in the inner ear. Hair cells in the cochlea
convert sound information into electrical signals that are sent to the brain. Once hair cells
die or are damaged – whether from noise, age, sudden deafness, or drugs – hearing is lost.
Because hair cells are not regenerated in humans or other mammals, most hearing deficits
are permanent. Birds and fish have the natural ability to regenerate damaged hair cells. Our
challenge is to replicate this regeneration in humans.
HRP consortium members discussing
their latest collaborative research.
5
Our Research Strategy
C
onsortium members of the Hearing Restoration Project (HRP) highlighted two major
issues with regard to our current understanding of hair cell regeneration. First, it is
clear that “supporting cells” of the inner ear give rise to new hair cells after injury. Yet we have
identified only a small number of molecules that influence the ability of supporting cells to
yield new hair cells.
Second, we know very little about how supporting cells change over time following hair
cell damage. This information is key for identifying potential targets for regeneration therapy.
The two general approaches outlined below are highly integrated and involve the efforts
of the majority of consortium members. We are hopeful that these approaches will lead to
development of a targeted strategy to promote hair cell regeneration in mammals in ten years.
PHASE I – Discovery Research (Years 1-5)
The goal of Phase I is to 1) discover the factors that block
regeneration, and 2) identify the missing factors that can promote
regeneration. Two broad approaches are envisioned.
Scientific Approach 1. Comparative Genomics: Genetic and epigenetic
regulation of pro-regenerative behaviors in supporting cells compared
across species
Diagram of the Inner Ear
We will determine how birds, fish, and mammals differ with respect
to gene expression after hair cell damage. This approach should
pinpoint biomarkers that are permissive or restrictive for supporting
cell division and transdifferentiation. Such biomarkers could include
individual transcription factors or complete signaling pathways.
These biomarkers will serve as the next targets for experimental
manipulation in vitro and in vivo. A related and complimentary
approach is to make similar comparisons between supporting cells
in the mammalian inner ear at different ages. Analyses will be done across laboratories, and
large amounts of genomic data will be generated. Experienced specialists will help extract the
data, and raw and processed data will be posted online for consortium members to view. This
process will allow immediate hypothesis generation and testing, which will hasten progress
toward our goals.
Scientific Approach 2. Cell Tracking Analyses: Supporting cell fate mapping in genetically
modified mice after injury
We need to know which cell types remain in inner ear epithelia (sensory tissue) at early and
late periods following different forms of damage to hearing and balance organs. We will use
transgenic mice to allow the identification and tracking of specific subtypes of supporting
cells or cells outside the sensory epithelium. This approach will use these mice to determine
the fates of all supporting cells in the mouse organ of Corti and in the utricle, a sensory organs
in the inner ear specialized for balance function, after different forms of hair cell damage
6
There’s a way to do
it better—find it.
—Thomas Alva Edison, Man of the
Millennium and American Innovator who
lived with a severe hearing loss
are induced. This analysis will also help identify markers for the cell types that remain after
damage, facilitating genetic manipulation of these potential target cells in future experiments.
PHASE II – Pre-Translational Research (Years 3-8)
In parallel with ongoing projects of Phase I, additional projects will be initiated to determine
how best to implement the results of Phase I. In addition, we will determine whether regenerated
hair cells are functional or whether other steps are required to restore hearing.
PHASE III – Translational Research (Years 6-10)
Phase III will entail pre-clinical translational research that implements strategies culminating
from research during Phases I and II. We estimate that Phase I will be completed in Years
Hearing Restoration Project
1-5, and we expect that early results in Phase II will allow us to start to establish new hair
Strategic Plan
cells in damaged mammalian ears by Year 6.
Projects in Phase III will focus on manipulating
specific target genes, pathways, and/or cells
in the injured mammalian organ of Corti and
utricle. Results from these projects will indicate
manipulations, or treatments, that will likely lead
Phase 1 Discovery Research
to improvements in hearing or balance function,
Years 1 - 5
first in animal models, and later in humans.
Conclusion:
Comparative genomics
Department of Otolaryngology/Head and Neck
Surgery and the Virginia Merrill Bloedel Hearing
Research Center, in Seattle, WA and Peter BarrGillespie, Ph.D., Scientific Director of the Hearing
Restoration Project and researcher at Oregon Health
& Science University.
Identify cells remaining in Organ of
Corti after damage
Animals that readily regenerate
Researchers estimate that with current levels
of funding in hearing science and without the
Hearing Restoration Project consortium, it
will take 50 years to achieve human inner ear
restoration. Today, through the collaborative
model of the Hearing Restoration Project and our
consortium of experts, we have the opportunity
to accelerate the research and shorten the timeline
for discovery to 10 years or less.
This strategy was summarized by Jennifer Stone,
Ph.D., and Edwin Rubel, Ph.D., members of
the Hearing Restoration Project consortium and
researchers at the University of Washington’s
Cell tracking analyses
Identify genes that drive supporting
cells to form new hair cells
Mature Zebrafish
Mature Chickens
Mouse
Organ of Corti
Degeneration
Developing Chicks
Developing Mouse
Genes
X, Y, Z
Mature Mouse
Animals that do not regenerate
Phase 2 Translational Research
Years 5 +
Drive remaining cells to form new hair cells
Regeneration
Genes
X, Y, Z
Damaged Mouse
Organ of Corti
Repaired Mouse
Organ of Corti
7
How You Can Help/
Funding Opportunities
R
arely have scientists had such a clear view of the nature of a cure for a major health
issue. We are tantalizingly close to it … yet there is much work still to be done. We
need your help. Please join Hearing Health Foundation and help us make hearing loss and
tinnitus a thing of the past.
The Hearing
Restoration Project
is the biggest reason
I contribute. Such an
organized effort, with
so many top-notch
scientists, provides
a real possibility that
Hearing Loss will
be cured.
—Anthony Bartoli,
a monthly donor who has hearing loss
Doug Olson, CFRE
Director of Development
[email protected]
(212) 257-6144
For more information and to learn more about funding opportunities contact:
Hearing Health Foundation
363 Seventh Avenue, 10th Floor
New York 10001-3904
or online at www.hhf.org/JoinUs.
We’ve made it easy to support Hearing Health Foundation and the Hearing Restoration
Project in the way that is most convenient for you:
• Naming Opportunities
• Major Gifts
• Tribute Gifts
• Monthly Giving
• Fundraising Events: Fundraise for a Cure for Hearing Loss
• Workplace Giving
• Gifts of Appreciated Stock or through your IRA
• Planned Giving Through Your Estate Plans (Collette Ramsey Baker Society)
• Name a Research Grant
• Partner With Us (companies and community groups)
Hearing Health Foundation Board of Directors
Shari S. Eberts, Chairman; Mark Angelo; Robert Boucai; Judy R. Dubno, Ph.D.; Rebecca Ginzburg; Roger M. Harris;
David S. Haynes, M.D.; Elizabeth Keithley, Ph.D.; Richard Miyamoto, M.D.; Michael C. Nolan; Paul E. Orlin; Chris
Smith; Peter Steyger, Ph.D.; Clifford P. Tallman, Jr.; Elizabeth Thorp; Ronald E. West, Nancy M. Williams.
Hearing Restoration Project Consortium Members
John Brigande, Ph.D.; Alain Dabdoub, Ph.D.; Albert Edge, Ph.D.; Andy Groves, Ph.D.; Stefan Heller, Ph.D.; Michael
Lovett, Ph.D.; Liz Oesterle, Ph.D.; Tatjana Piotrowski, Ph.D.; David Raible, Ph.D.; Yehoash Raphael, Ph.D.; Ed Rubel,
Ph.D.; Neil Segil, Ph.D.; Jennifer Stone, Ph.D.; Mark Warchol, Ph.D.
Hearing Health Foundation is a non-profit 501 (c)(3) tax exempt charity (Tax ID: 13-1882107).