Download HLAA recently reprinted an article published in January by the New

HLAA recently reprinted an article published in January by the New York Times. It quotes
HLAA Board Member and leading hearing loss researcher, Dr. Frank Lin. The article reviews a
cross section of hearing loss research addressing loss from meningitis, Muniere’s, age and more.
It is lengthy but if you have an interest in the state of research, it is an excellent overview.
Special note—see the discussion, bolded, of the first human experiment of gene therapy aimed at
regenerating hair cells
From Vertigo to Tinnitus, Ear Ailments Are New Focus for Drugs
By ANDREW POLLACK
JAN. 9, 2015
There is a huge need, some experts say. About 48 million Americans have a meaningful hearing
loss in at least one ear; 30 million of them have it in both ears, said Dr. Frank R. Lin, an
associate professor of otolaryngology and geriatric medicine at Johns Hopkins University. That
figure is expected to increase as baby boomers grow older.
A drug to treat or prevent age-related hearing loss “will be something that people take every day
for the rest of their life,” said Edwin W. Rubel, a professor of hearing science at the University
of Washington and co-founder of a start-up called Oricula Therapeutics. “Even if it could just
delay age-related hearing loss by five or 10 years, that would be wonderful.”
Of course, many people with hearing problems can use hearing aids or, for serious cases,
cochlear implants. But the implants require surgery and many people do not like or use hearing
aids, so drugs could be an alternative.
“Glasses can usually return you to 20/20 while hearing aids don’t return you to normal hearing,
not even close,” said Kathleen C.M. Campbell, a professor at Southern Illinois University School
of Medicine.
But challenges remain. Efforts in the past to develop ear drugs, to the extent they were made,
largely failed. The inner ear, which is crucial to both hearing and balance, is almost
impenetrable, making it difficult to study or for drugs to enter.
“It’s a teeny organ encased in a really, really hard bone,” said Dr. Hinrich Staecker, professor of
otolaryngology at the University of Kansas School of Medicine. “The whole inner ear fits inside
the tip of your pinkie.”
Executives at the new companies say that genetic and animal studies are revealing more about
how the ear works. They note that the pharmaceutical industry once also neglected the back of
the eye. Now there are blockbuster drugs like Genentech’s Lucentis and Regeneron’s Eylea that
are injected into the eye to stave off blindness from retinal diseases. The ear, they say, is the new
eye.
But maybe not for Rob Gerk, a 31-year-old man in Denver who lost most of his hearing
when he had meningitis as a toddler. He is the first patient in a clinical trial of gene therapy
aimed at regenerating hair cells. The trial is being sponsored by Novartis and uses a gene
therapy developed by GenVec, a Maryland biotech company.
In late October, Mr. Gerk underwent surgery by Dr. Staecker at the University of Kansas
to infuse viruses carrying a gene called Atoh1 into his right inner ear. Atoh1 causes cells in
a fetus to become hair cells. It is hoped that some of the supporting cells in the inner ear
will take up the gene and turn into hair cells.
The companies said it would take two months to tell if the therapy was working, a time
period that just passed. Mr. Gerk said there was no significant change but there may have
been more subtle effects. “I have incidents where I think I’m hearing a new sound or
hearing sound differently than I did before,” he said by email.
Other companies are trying either to improve hearing or prevent loss of hearing from trauma like
loud noises or exposure to the chemotherapy drug cisplatin or a widely used class of antibiotics
known as aminoglycosides.
Auris Medical, a Swiss company, said that its experimental drug AM-111 improved hearing and
speech discrimination compared with a placebo in people who were treated within 48 hours of
suffering a hearing loss. But the drug was effective only for those with serious hearing loss, not
mild or moderate. The drug was delivered by a single injection through the ear drum into the
middle ear, from which it diffused into the inner ear.
Sound Pharmaceuticals of Seattle says its drug, intended to reduce oxidative damage to the ear,
helped prevent temporary hearing loss compared with a placebo in young adults with normal or
near-normal hearing who listened to four straight hours of loud music through headphones.
Autifony Therapeutics is conducting early trials of a daily pill aimed not at hair cells but at
helping the brain better interpret signals from the auditory nerve.
“You can only hear what your brain allows you to hear,” said Barbara Domayne-Hayman, chief
business officer at the company, which was spun out of GlaxoSmithKline and is based in Britain.
“We’re basically trying to get the neurons to fire properly again.”
One sponsor of research in the area is the Defense Department, which cannot redeploy many
soldiers because they have hearing loss. At Fort Jackson, S.C., drill sergeant trainees fire 500
rounds from extremely loud M16 rifles over the course of 11 days. Dr. Campbell of Southern
Illinois University is running a study there to test if d-methionine, an amino acid that is said to
reduce oxidative damage, can help preserve their hearing.
Companies are also working on drugs for tinnitus, in which sound is perceived without a source
of the sound being present. Roughly 10 percent of American adults, or 25 million people, have
experienced at least one episode lasting five minutes or more in the last year, according to the
National Institute on Deafness and Other Communication Disorders.
Tinnitus can be caused by many things, including hearing loss. Treatments include behavioral
therapy and devices that can mask the sound. But many of those just help people tolerate the
condition, not get rid of it. Some drugs like steroids and lidocaine are used off label.
Auris is in late-stage trials of AM-101, a derivative of the anesthetic ketamine, which it hopes
will dampen the aberrant signaling in the auditory nerve that is perceived as tinnitus. In a
midstage trial, the drug, injected into the middle ear, was not more effective overall than a
placebo. But a subset of patients whose tinnitus was caused by trauma or infection said the drug
made the sound in their ears softer, less annoying and less disruptive of sleep.
Investors appear to be cautious given the challenges. Auris went public on Nasdaq in August at
$6 a share, using the trading symbol EARS. The stock is now trading at about $4.
Otonomy’s stock, by contrast, has roughly doubled since its August initial public offering. That
is perhaps because for now it is pursuing what might be more tractable problems.
When Mr. Lichter suffered his first attack of Ménière’s, he received steroids, a commonly used
off-label treatment. But when the drug is injected into the middle ear, patients have to lie on their
sides for 30 minutes and not swallow to try to keep the drug from draining into the throat through
the Eustachian tube.
Otonomy, based in San Diego, developed a way to deliver the steroids as a gel that does not
readily drain away after injection. The company has started the final stage of trials for the
Ménière’s product. It hopes its first product — it will apply for regulatory approval in the first
half of this year — could be a gel form of an antibiotic to be injected to treat middle ear
infections, an alternative to ear drops.
Mr. Lichter said the intense bouts of vertigo, which left him bedridden two or three times a week,
have not returned in four years. But he has constant ringing in his left ear and can barely hear
through it.
Mr. Lichter, a managing director at Avalon Ventures in San Diego, said that although he had
helped start 15 or 20 companies, “This is the one that is special to me.”
NEW STUDIES ON RESTORING INNER EAR HAIR CELLS
“Michigan Today” has reported on research where scientists have restored the hearing of mice
partially deafened by noise. They used advanced tools to boost the production of a key protein in
their ears. They reported in November that: “By demonstrating the importance of the protein,
called NT3, in maintaining communication between the ears and brain, these new findings pave
the way for research in humans that could improve treatment of hearing loss caused by noise
exposure and normal aging...
That’s music to the ears of anyone who has experienced problems making out the voice of the
person next to them in a crowded room, or struggled with temporary reduction in hearing after a
loud concert”.
Dr. Gabriel Corfas who led the research team at the University of Michigan’s “Kresge Hearing
Research Center” said that this has been an ongoing project for 15 years. The research attempts
to answer the questions “about the inner ear, and now we have been able to restore hearing after
partial deafening with noise, a common problem for people”.
Michigan Today stated that “Their work also illustrates the key role of cells that have
traditionally been seen as the ‘supporting actors’ of the ear-brain connection. Called supporting
cells, they form a physical base for the hearing system’s ‘stars’: the hair cells in the ear that
interact directly with the nerves that carry sound signals to the brain. This new research identifies
the critical role of these supporting cells along with the NT3 molecules they produce.
NT3 is crucial to the body’s ability to form and maintain connections between hair cells and
nerve cells, the researchers demonstrate. This special type of connection, called a ribbon
synapse, allows extra-rapid communication of signals that travel back and forth across tiny gaps
between the two types of cells”.
The research study can be found at:
http://elifesciences.org/content/early/2014/10/17/eLife.03564