Inner Ear Treatments Cochlear Implants Hearing Loss and More: Advances in Otolaryngology

Summary

In this Brain Channel interview, Dr. Jeff Harris, a distinguished professor of Otolaryngology, discusses his extensive career and groundbreaking research. He shares insights into his work on autoimmune ear diseases, the development of innovative drug delivery systems, and the transformative impact of cochlear implants on hearing loss. Dr. Harris also highlights ongoing research in hair cell regeneration and the challenges posed by HPV-related cancers. The conversation emphasizes the significance of translational research and the future advancements in otolaryngology that aim to improve hearing and quality of life for aging populations.

Takeaways

• 🔬 Dr. Jeff Harris is a distinguished professor of Otolaryngology and has been at his current institution for 38 years.
• 📚 Dr. Harris originally trained in Boston at Harvard and holds a PhD in Immunology.
• 🦻 His research shifted from general head and neck surgery to ear diseases, specifically exploring the immune responses in the inner ear.
• 🧪 His lab discovered that the inner ear is not immune-privileged and has a robust immunological response, particularly in the endolymphatic sac.
• 💉 Dr. Harris developed a new treatment involving a sustained-release gel for drug delivery to the inner ear, leading to the creation of a company called Autonomy.
• 👂 Dr. Harris was involved in the development of cochlear implants, which have significantly improved the quality of life for deaf patients.
• 🧠 Functional MRI studies have shown brain plasticity in patients with cochlear implants, indicating that the brain can adapt to new auditory inputs.
• 🔬 The Otolaryngology division is also focused on HPV-related oropharyngeal cancers and developing rapid screening tests.
• 👴 Hearing loss is a major issue among the elderly, with ongoing research into regenerating hair cells and neurons to improve hearing.
• 🛡️ Prevention of hearing loss through protective measures is crucial, as noise exposure is a significant factor in developing deafness and tinnitus.

Q & A

Who is Dr. Jeff Harris and what is his current position?

Dr. Jeff Harris is a distinguished professor of Otolaryngology in the Department of Surgery and the head of the division of Otolaryngology.

What is Dr. Harris's background in terms of education and training?

Dr. Harris completed his training in Boston at Harvard, has been with his current institution since 1979, and holds a PhD in immunology.

What was Dr. Harris's initial area of specialization when he started his career?

Dr. Harris started his career as a head and neck surgeon, not as an ear doctor.

What discovery by Professor Bryan McCabe influenced Dr. Harris's research direction?

Professor Bryan McCabe discovered that some ear diseases and hearing loss might be autoimmune in origin, which influenced Dr. Harris to investigate this area.

What significant finding did Dr. Harris's laboratory discover about the inner ear?

Dr. Harris's laboratory discovered that the inner ear has a robust immunological response, particularly involving the endolymphatic sac, which acts as the lymph node of the inner ear.

What innovative treatment method did Dr. Harris help develop for ear conditions?

Dr. Harris helped develop a sustained release gel for drug delivery into the ear, which is thermo-reversible and can hold drugs like dexamethasone.

What is the name of the company that Dr. Harris helped found, and what is its purpose?

The company is called Autonomy, and it focuses on developing treatments and drug delivery methods for ear conditions.

What is a significant milestone achieved by Autonomy?

Autonomy developed an FDA-approved antibiotic suspended in a gel for children with middle ear infections, which allows for sustained drug release and eliminates the need for ear drops.

How does a cochlear implant work, according to Dr. Harris?

A cochlear implant consists of electrodes surgically placed in the inner ear that stimulate surviving neurons to transmit sound signals to the brain, allowing deaf patients to hear.

What advancements have been made in the indications for cochlear implants?

Cochlear implants are now used not only for patients with bilateral profound deafness but also for those who can still hear with a hearing aid, providing a full range of auditory fidelity.

What current research is being conducted on the brain's response to cochlear implants?

Researchers are using functional MRIs to study how the brain's circuits adapt and change in response to cochlear implants, showing plasticity in tone-atopic organization.

What new area of concern in Otolaryngology is related to HPV?

There is a growing epidemic of HPV-related oropharyngeal cancer, affecting people who are not traditional smokers or drinkers, requiring new treatments and surveillance methods.

What innovative screening method is being developed for HPV-related cancer?

One of the faculty is working on a rapid spit test for screening individuals at risk for HPV-related cancers.

What is the future direction of research in hearing loss prevention and treatment?

Future research aims to regenerate hair cells and neurons using growth factors and drug delivery methods, potentially restoring hearing in aging populations.

What common causes of hearing loss are highlighted by Dr. Harris?

Noise exposure is a significant cause of hearing loss, and prevention includes using ear protection in noisy environments to prevent hearing damage and tinnitus.

Outlines

00:00

🎓 Introduction to Dr. Jeff Harris and His Work

Bill Mobley introduces Dr. Jeff Harris, a distinguished professor of Otolaryngology at the University of California, San Diego. Dr. Harris shares his extensive background, including his PhD in immunology and his career spanning 38 years. He discusses the unexpected direction his research took, focusing on the immunological aspects of ear diseases and hearing loss. His work includes significant discoveries about the ear's immune responses and the development of treatments for autoimmune-related hearing loss.

05:02

💉 Innovative Treatments for Ear Conditions

Dr. Harris describes the development of a new drug delivery method for treating ear conditions, involving a thermo-reversible gel that stays in place upon reaching body temperature. This gel can be used to deliver drugs like dexamethasone directly into the ear. This innovation led to the creation of a company called Autonomy, which now employs 160 people and has developed FDA-approved treatments such as a sustained-release antibiotic gel for children with middle ear infections.

10:03

🦻 The Evolution and Impact of Cochlear Implants

Dr. Harris talks about the groundbreaking technology of cochlear implants, which he first performed in San Diego in 1985. These implants have evolved from crude devices to sophisticated systems with multiple electrodes that stimulate specific neurons, allowing deaf individuals to hear. He explains how the brain adapts to these implants, interpreting the signals as sound, and highlights the transformative impact they have on patients' lives.

15:05

🔬 Future Directions in Otolaryngology and Brain Adaptation

Dr. Harris discusses future projects in the field of Otolaryngology, including the treatment of HPV-related oropharyngeal cancers and the potential for regenerating hair cells in the ear to combat age-related hearing loss. He emphasizes the importance of preventing hearing loss through noise protection and explores the possibilities of using growth factors to stimulate hair cell and neuron regeneration. The conversation concludes with reflections on the ongoing challenges and advancements in hearing restoration and protection.

Keywords

💡Otolaryngology

Otolaryngology, also known as ENT (ear, nose, and throat), is a medical specialty focusing on the diagnosis and treatment of disorders of the head and neck, including the ears, nose, and throat. In the video, Dr. Jeff Harris discusses his extensive work in this field, including head and neck surgery and treating ear diseases.

💡Immunology

Immunology is the study of the immune system, including how the body defends itself against disease. Dr. Harris, with a PhD in immunology, applied his knowledge to investigate immune responses in the inner ear, leading to the discovery that the ear has a robust immunological response, contrary to previous beliefs.

💡Inner ear

The inner ear is the innermost part of the ear, responsible for hearing and balance. Dr. Harris's research focused on the immunological aspects of the inner ear, discovering its immune response capabilities and the role of the endolymphatic sac as the lymph node of the inner ear.

💡Endolymphatic sac

The endolymphatic sac is part of the inner ear involved in fluid resorption and immune responses. Dr. Harris's studies revealed its function as a lymph node of the inner ear, playing a crucial role in the ear's immune system.

💡Autoimmune

Autoimmune refers to a condition where the body's immune system attacks its own tissues. Dr. Harris explored the idea that some ear diseases and hearing loss might be autoimmune in origin, leading to new diagnostic and therapeutic approaches for these conditions.

💡Cochlear implant

A cochlear implant is a medical device that provides a sense of sound to a person with severe hearing loss. Dr. Harris performed the first cochlear implant in San Diego in 1985 and discussed the device's ability to stimulate surviving neurons in the inner ear, allowing the brain to interpret sounds.

💡Translational research

Translational research involves applying basic scientific discoveries to develop practical medical treatments. Dr. Harris's work is a prime example, as he translated his basic research on the ear's immune responses into new therapies for hearing loss and ear diseases.

💡Thermo reversible gel

Thermo reversible gel is a substance that changes from liquid to gel at body temperature. Dr. Harris developed a gel-based drug delivery system that remains liquid when injected into the ear but gels at body temperature, allowing for sustained drug release directly to the inner ear.

💡HPV (Human Papillomavirus)

HPV is a virus that can cause oropharyngeal cancers. Dr. Harris highlighted the rise of HPV-related head and neck cancers in non-smokers and non-drinkers, emphasizing the need for new treatments and early detection methods, such as a spit test for rapid screening.

💡Hair cells

Hair cells are sensory cells in the inner ear that convert sound vibrations into electrical signals for the brain. Dr. Harris mentioned the potential for regenerating hair cells using growth factors, which could lead to new treatments for age-related and noise-induced hearing loss.

Highlights

Dr. Jeff Harris is a distinguished professor of Otolaryngology with 38 years of experience.

Started training in Boston at Harvard, moved to San Diego as a head and neck surgeon in 1979.

Developed research indicating that the ear has a robust immunological response.

Identified the endolymphatic sac as the lymph node of the inner ear.

Investigated immune responses in the ear, leading to diagnostic methods and treatments for ear diseases.

Developed a method to inject drugs through the eardrum for better absorption into the inner ear.

Co-founded a company, Autonomy, that developed a sustained-release gel for drug delivery in the ear.

Created an FDA-approved antibiotic gel for children, eliminating the need for ear drops.

Performed the first cochlear implant in San Diego in 1985, significantly improving the lives of deaf patients.

Cochlear implants stimulate neurons in the inner ear, allowing the brain to interpret sound and other auditory information.

Research shows brain plasticity allows adaptation to cochlear implants, even with frequency shifts.

Ongoing work includes treating HPV-related oropharyngeal cancers and developing rapid screening tests.

Exploring regenerative treatments for hearing loss, focusing on hair cell and neuron regrowth.

Emphasizes the importance of hearing protection to prevent noise-induced hearing loss and tinnitus.

Predicts future advancements in drug delivery systems and treatments to improve hearing in the elderly.

Transcripts

[Music]

greetings bill Mobley for the brain

channel happy to be with you today and

to be with Jeff Harris dr. Jeff Harris's

distinguished professor of

Otolaryngology in the Department of

Surgery and the head of the division of

Otolaryngology Jeff it's great to have

you here I wanted to have you tell us a

bit about your background and about the

work that you and your division do and

also about the exciting research that's

going on in your group happy to do so

well I've been here I'm one of the

senior seniors now hard to believe that

I've been here 38 years started 1979

having finished training in Boston at

Harvard and came here with a PhD as well

and immunology where I thought

immunology was going to take me in my

training has ended up being completely

different of course

what's interesting was when I finished

my training in Boston I came to San

Diego as a head and neck surgeon not as

an ear doctor and right about that time

there was a professor at University of

Iowa named Bryan McCabe who's very

well-known professor in those days who

serendipitously came upon the idea that

ear ear diseases and some some hearing

loss might be autoimmune and origin and

he wrote a classic paper then that I

read and with my background in

immunology I said well that's an area

that I ought to be investigating and so

I set about doing some basic science

research on whether the ear like what

was thought to be the brain whether it

was immuno privileged and turns out that

it isn't and it turns out from the basic

science studies that our laboratory did

that the ear has a relatively robust

immunological response that there

appears to be in the inner ear a organ

called the endolymphatic sac which is

what is thought to be responsible for

fluid resorption but it turns out that

it's the lymph node of the inner ear and

we did studies to

look and see whether or not that organ

if disconnected from the ear surgically

in experiments that we were doing might

it prevent the ear from responding and

Mina logically and in fact it did so we

developed this new area of research and

scientific investigation that involved

the inner ear immune responses it turns

out that patients also have conditions

that are immunologic rheumatologic viral

that provoked the immune response and

affect their hearing and so over the

years we've developed methods of trying

to diagnose them including an antibody

test I developed and also ways in which

we can begin to give them better

therapies as you know with many

rheumatologic diseases you have to treat

them with high-dose steroids steroids

have a lot of systemic side effects and

so we began to look at could you develop

a treatment where you would be injecting

these in these drugs directly through

the eardrum and get absorbed into the

inner ear it turns out that if you take

drugs that are off the shelf and inject

them through the eardrum and have the

patient lay on their side and try to

have that drug absorbed into the inner

ear what happens as soon as they swallow

it goes down the eustachian tube and the

drug dissipates or as soon as they stand

up it comes out through the hole that

you use to inject the drug in the ear so

I had the good fortune to run into a

venture capitalist in San Diego who had

an inner ear problem and we talked about

a new therapy for his condition whereby

we would inject a drug into his ear so

he underwent the treatment that I did

and in fact it it helped him

tremendously and he came back and he

said to me well you know that's a great

idea why don't we sit down and think

about how we can develop a company that

might be able to develop these kinds of

treatments and in drug delivery that

would be much more satisfactory to help

patients so it turns out that with a lot

of preclinical research that

he and his people that were hired to

investigate this and our own expertise

and help and guide them as to how to do

this we developed a sustained release

chemical a gel that is thermo reversible

meaning that if it's in the out here

it's in a liquid form but as soon as it

hits body temperature gels so we can

then embed into this gel a drug such as

dexamethasone and have it as a liquid

form injected into the ear and then as

soon as it hits the body's temperature

it forms a gel and stays there for

several weeks and so we've now developed

a company in around this idea

it's called autonomy and here in San

Diego it's a now company that has 160

employees and it now has a antibiotic

that we have suspended in this gel that

allows children to get one injection

through and timpanist amitabh those

little tubes that you use for fluid that

builds up in the middle ear of kids and

they don't have to use air drops and so

this is an antibiotic that will stay

around for two weeks and they know the

parents don't have to put drops in their

ears

there's no screaming it's just a

sustained release drug and it's now FDA

approved and it's being commercialized

today so an example really of having a

basic interest in science but also a job

that brings you to the to the care of

patients and you put those two things

together and some pretty surprising

things can emerge yes I guess that's

what's translational research you know

in the true sense of the word Jeff

you've been involved in a number of

projects the cochlear implant is an

interesting really interesting not just

from a therapeutic perspective but

interesting and in terms of the way the

brain interprets the information coming

from the implant speak a little bit

about that if you will yeah it's it's a

miracle really I can't think of anything

that is equivalent to it that we

currently have I mean a lot of things

happening in the eye but there's nothing

as advanced as cochlear implants for

patients that are deaf

and I did the first cochlear implant in

San Diego 1985 it was in those days a

very crude device electrode that you

would put surgically into the inner ear

with the notion that these electrodes

would lay up against the neurons that

were still surviving within the inner

ear of a deaf patient because as you

know hearing is a conductive the eardrum

the ear canal the little bones and that

takes sound into the inner ear that

stimulates hair cells the hair cells are

what create an electrical impulse and

that gets transmitted through the

neurons to the brain and in many deaf

patients the hair cells go

but the neurons survive or a portion of

the neuron survive so and because the

cochlea is a snail shell in terms of its

anatomy in the way it's designed it's a

perfect in atomic configuration to allow

an electrode to lay up against a

surviving neuron at a specific frequency

and so these current devices have 22 to

24 electrodes each one lays against the

center of the cochlea and it stimulates

a neuron with a specific frequency that

it's capable of receiving and at that

point the brain will pick up what is now

a different way of hearing and be able

to interpret that as sound and in case

in some cases music and in some cases

everything in their environment it's

it's absolutely fascinating that you see

a individual who has been deaf for many

years and was once a hearing person and

you turn this device on and within a few

weeks they even immediately they'll say

I got back into my car and I couldn't

believe what what was the sound I was

hearing and it was the turn signal that

they were hearing for the first time in

15 years so it's a device that works

beautifully well in people who are

deafened and now the indications have

been extended to people not only who

have bilateral profound

toughness but who can still hear with a

hearing aid and you are able to implant

an electrode that

augments the high frequencies and they

have preserved low frequencies so that

can wear a hearing aid and the Allah in

the device itself so it gives them a

full range of fidelity that they would

not get in previously you know it's it's

very clear that the brain learns how to

listen to the implants it learns how to

listen to all kinds of other information

coming in orally that are it's pretty

indistinct but you teach it a little bit

and it'll earns a lot what do we know

about how the brain changes in people

with a cochlear implant do we know how

the brain circuits are modified is there

some inference I'd into that there are

places that are doing functional MRIs

with people who have been implanted and

have looked to see whether or not there

are certain areas of the brain that have

taken over and what's interesting is

that you can take an electrode that

should be only for the high frequencies

and it doesn't reach into the areas of

the low frequencies and yet once the

patient gets the ability to listen and

learn in the it'll fill in these areas

and they will actually be getting low

frequencies where the electrode should

be laying up against a mid or high

frequency fiber and so there's some

plasticity that occurs and allows there

to be a shift in the tone atopic

organization of the brain to you know

reinterpret what they're hearing as

higher frequencies or lower frequencies

it's great stuff it's really so

fascinating I mean this is the brain

channel so we're obviously extremely

excited about the brain and and I think

we've just scratched the surface on

understanding how it takes in sensory

information talk about the near future

for your own work and for the work of

the division what what are the projects

you have in mind well Otolaryngology is

a big field it's we think of ear nose

and throat but in fact we do head and

neck can't

we take care of all of the serious

cancers that develop in the

oropharyngeal areas the larynx the face

and in deep to the face we do skull base

surgery which is sort of a no-man's land

between the inner ear and the

neurosurgical parts of the skull and

right now what's really become

fascinating is the the epidemic of HPV

as a cause for or pharyngeal cancer it's

become very well recognized that HPV

affects people who are not the smokers

and the drinkers and so we have a whole

cadre of people who have developed or

pharyngeal cancers that are due to a you

know human papilloma virus and so the

treatments that we can now afford them

and the surveillance that we now have to

do has changed immensely in the last

five years and so there's going to be an

onslaught of more patients who come

through with HPV related cancers and you

guys are developing the special

abilities necessary to be the expert

site for evaluating and caring for those

patients we one of our faculty is in

fact working on a spit test that would

allow us to do rapid screening of people

who may or may not be at risk for HPV

cancer interesting

Jephthah works exciting interesting it's

hard to believe that Otolaryngology is

is is going to go out of style one of

the one of the major challenges that I

think will face us after we've dealt

with these degenerative diseases of the

brain and after we've dealt with stroke

I think of course we're going to we're

going to have better ability to manage

all that maybe even prevent it we're

still going to have old folks that have

trouble hearing and seeing and my guess

is that hearing is going to be just as

much it just as important seeing for

those folks that are in their 90's or

you know beyond 100 any thoughts about

what that looks like what are we going

to have available for those folks as

they age well it's interesting because

greater than 50 percent of people over

75 are have hard our hard-of-hearing you

have

and between the ages of 64 and 7075

there are about a third of people who

have significant hearing loss so we're

we're all looking for ways to regenerate

hair cells find growth factors neuro

neuro growth factors that will stimulate

the regrowth not of just the hair cells

but of neurons as well and what we're

finding is that the supporting cells

that lay underneath the hair cells can

regenerate hair cells so with the proper

stimulation they can be turned from just

supporting cells to new hair cells and

in lower species this happens all the

time

in chickens for instance if you wipe out

their hair cells they will greet grow

new hair cells and there are some

mammals that we're beginning to tease

apart the signals that prevent them from

regenerating so that their hair cells

can regenerate and it's only a matter of

time we hope that we will be having drug

delivery like I mentioned earlier for

growth factors that can be put into a

person's middle ear get absorbed into

the inner ear and within you know months

their hair cells start sprouting so to

speak and that would be the greatest way

we can regenerate hair cells and in

people who are beginning to lose their

hair cells as they age one of the

important things of course is prevention

of hearing loss and many people create

their own problem by noise exposure and

we know that that's a big factor for the

development of progressive deafness and

patients and people who you you see

every day out there on the streets

they're workers they're construction

people and they're in there with the

jackhammers and they don't wear hearing

protection or they're carpenters are

working in shops where they you know

don't protect themselves and all they

have to do is wear some ear protection

and they will prevent not only hearing

loss but the other thing that's so

plaguing of people is tinnitus the

ringing part of the

symptomatology that goes along with

deafness Jeff great to talk with you

great to hear about all the advances and

here's looking forward to a great future

in which all of us are able to hear a

little bit better yes I hope some we do

good thank you bill mably for the brain

channel

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[Music]

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