Ongoing Research on Treatments for Tinnitus, Hearing Loss, and Hyperacusis
Below is a summary of some of the most important studies
currently underway for the treatment of various auditory disorders. The vast
majority of these studies aim to regenerate or even promote the creation of new
auditory cells, with broad implications, as they could potentially reverse
conditions such as hearing loss, hyperacusis, and tinnitus.
The studies are listed in chronological order, from the most
recent to the oldest, based on the publication date (or the date it was
mentioned) in the consulted source:
2024
2024 (USA). Dr. Daniel B. Polley, professor at
Harvard University, along with his team, succeeded in stopping hyperacusis in
laboratory experiments with mice and hopes to eventually replicate this in
humans using a non-invasive method. (click here to read more)
2023
Aug 2023 (Argentina). A team of Argentine researchers
led by Dr. María Eugenia Gomez-Casati from the Institute of Pharmacology
(Faculty of Medicine, University of Buenos Aires) discovered a link between
age-related hearing loss and a decrease in cholesterol levels in the inner ear.
This reduction affects the outer hair cells, which play an essential role in
amplifying sound. In experiments with mice, they found that over-the-counter
phytosterol supplements (plant-based compounds) were effective in compensating
for this cholesterol loss and maintaining outer hair cell function. This
potential solution for hearing loss could also help resolve tinnitus in
patients who experience it.
Jun 2023 (USA). A study led by researcher Jung-Bum
Shin, PhD, revealed that auditory hair cells can self-repair damage caused by
loud noises or other stressors, challenging previous beliefs about their
irreversibility. The hair cells achieve this repair using a protein called
XIRP2, which detects damage to structures known as stereocilia and restores
them by replenishing new actin (the protein that forms the core of the cells).
The National Institutes of Health awarded over $2.3 million to fund further
research into this self-repair mechanism, which holds promise for future
treatment strategies for hearing loss and related conditions.
2022
Nov-2022 (Mexico). Studies conducted in several
countries (including Mexico) on Alpha Lipoic Acid, a fatty acid and antioxidant
found in potatoes (specifically in the skin protein) and other foods (also
naturally occurring in the body, but in low quantities), have shown positive
results in reducing tinnitus intensity through the intake of this compound (one
of its forms is a pill), over a three-month period. It is claimed that this
protein has the ability to regenerate hair cells and the middle ear in general.
Mar-2022 (Iran). Researchers from various Iranian
universities and institutions found that the herbal combination of Rosa Canina,
Urtica Dioica, and Tanacetum Vulgare (marketed as Neurotec capsules), together
with counseling, significantly reduced tinnitus symptoms and several of its
comorbid effects after three months of use in the treated patients.
Apr-2022 (USA). Entrepreneur Elon Musk announced that
his neuroprosthetic device, called Link—developed by his start-up
Neuralink—will be able to cure tinnitus within five years (that is, by 2027).
However, it still needs to be proven not only that it works, but also that it
is safe for humans, since it is an invasive method (already tested in animals).
Jan-2022 (USA). After reviewing several cases,
researchers Colby Skinner and Sanjeev Kumar from the University of Florida
found that ultrasound-guided blockage of the greater occipital nerve helped
reduce symptoms in patients with otalgia (ear pain) and associated tinnitus.
2018
Nov-2018 (USA). Dr. Thanos Tzounopoulos and his
research team at the University of Pittsburgh continued their investigations
related to the drug Retigabine, now with a project funded by the U.S.
Department of Defense. They had previously redesigned the structure of this
drug to target two potassium transport channels, KCNQ 2 and 3, enhancing
activity in both (see also the study from Mar-2016/USA below). This redesigned
compound, now called RL-81, will undergo new animal trials to improve
its effectiveness in reducing tinnitus symptoms. In the second part of the
project, the team will analyze and evaluate another ion channel, known as HCN,
which has shown reduced activity in mice after exposure to loud noise. The hope
is that a combined drug that increases the activity of potassium channels KCNQ
2 and 3 while reducing the activity of the HCN channel may prevent tinnitus in
susceptible individuals.
Nov-2018 (USA). With funding from the organization Action
on Hearing Loss, and under the direction of Drs. Mike Bowl and Ronna
Hertzano, research has been ongoing into the gene Ikzf2, which encodes
the Helios protein—a transcription factor that controls other genes. It has
been found that Helios is actively involved in the formation and proper
functioning of outer hair cells (which amplify sound signals), and that it also
influences other genes within these cells. Additionally, mutations in this gene
appear to alter the movement of these outer cells, affecting how they amplify
sound and potentially leading to hearing loss. This discovery suggests that
activating this gene correctly could regenerate outer hair cells, and thereby
lead to the development of treatments to restore hearing—potentially
eliminating certain types of tinnitus—via gene therapy, stem cell therapy, or
pharmaceutical approaches.
October 2018 (USA). Researchers in the United States
discovered that a group or family of proteins known as EGFR (Epidermal Growth
Factor Receptors), which is involved in the regeneration of cells in various
organs, may also aid in the regeneration of hair cells in the ear. This protein
family is known to play a role in the regeneration of avian hair cells by
stimulating supporting or progenitor cells (see the MIT study from Feb-2017
below). In particular, the ERBB2 protein—part of the EGFR family and present in
the vestibular system of the inner ear—has been identified as a promising
target. The goal is to develop drugs that can act on these proteins to promote
the regeneration of hair cells, thereby restoring hearing loss caused by damage
to these cells. The study was conducted at the University of Rochester and led
by Dr. Patricia White.
October 2018. Dr. Lawrence Lustig and his research
team at Columbia University, supported by the Swiss pharmaceutical company
Novartis and the American biotech firm GenVec, have been working on a gene
therapy known as CGF166. The therapy’s key ingredient is the Atoh1 gene, which
they are introducing into the ear to promote the transformation of supporting
cells into hair cells, with the aim of restoring auditory function. See earlier
studies listed under April 2017 (USA).
October 2018 (USA). A research team at the University
of California, San Francisco, led by Dr. Elliott Sherr, discovered that the
presence of the Tmtc4 gene in the brains of mouse embryos is crucial for the
later development of hearing. A lack of this protein—potentially caused by
exposure to loud noise—activates a cellular quality control system called UPR,
which triggers the self-destruction of hair cells, leading to deafness. The
goal was to find a way to block the UPR response and prevent the destruction of
hair cells. Fortunately, as early as 2013, an experimental drug had been
identified that could achieve this. When tested in mice exposed to loud noise,
it prevented damage to their hair cells and the resulting hearing loss. It is
hoped that this strategy can also be applied in humans to prevent various types
of hearing loss.
September 2018 (Sweden). A team of scientists led by
Dr. François Lallemend at the Karolinska Institutet, using a new single-cell
RNA sequencing technique in mice, discovered that there are three distinct
types of nerve cells—not just one—that transmit auditory signals to the brain.
They also mapped which genes are active in each cell type. This discovery could
lead to the development of new genetic tools, therapies, and drugs for treating
auditory disorders such as tinnitus, hearing loss, and hyperacusis, as well as
the creation of improved auditory devices like cochlear implants.
July 2018 (United Kingdom). A major study led by Dr.
Liz Marks from the University of Bath and Dr. Laurence McKenna from the
University College London Hospitals NHS Foundation Trust (UCLH), funded by the
British Tinnitus Association, found that Mindfulness-Based Cognitive Therapy (MBCT)
is significantly more effective than traditional relaxation-based treatments in
reducing tinnitus symptoms. The study showed that MBCT could make tinnitus less
distressing and intrusive over a longer period of time. The approach encourages
patients not to avoid the experience of tinnitus but to pay attention to it and
accept it. While MBCT may not be suitable for everyone, the researchers believe
it could become an increasingly viable option for patients who have not found relief
through conventional treatments.
Mar 2018 (USA). The biopharmaceutical company Otonomy
continues its work on the use of glacyclidine, an NMDA receptor
antagonist (N-methyl-D-aspartate), to treat tinnitus via intratympanic
injection. In its Phase I trial, this injection was named OTO-311, but it has
since been improved and renamed OTO-313, with Phase 1/2 trials expected to
begin in the first half of 2019. See earlier studies from Feb 2014, listed
below.
Jan 2018 (USA/Canada). A study published in January
2018, led by researchers including Kendra L. Marks, Susan E. Shore, and Larry
E. Roberts, once again demonstrated the benefits of bimodal stimulation: both
auditory and somatosensory. Unlike other methods of stimulation (see below the
vagus nerve stimulation work of Feb/Aug 2014 by Michael Kilgard and Sven
Vanneste), this approach involves stimulating the dorsal cochlear nucleus (the
first station where auditory signals from the ear arrive) using light pulses
applied to the cheek or neck. The auditory stimulation consisted of brief
sounds delivered through headphones. While only two participants reported
complete elimination of their tinnitus, several indicated that their tinnitus
felt less severe. One major advantage of this stimulation method is that it has
no side effects and is non-invasive, unlike other techniques such as deep brain
stimulation or vagus nerve stimulation.
2017
Aug 2017. A study led by Fatima Husain, professor at
the University of Illinois, found that chronic tinnitus is localized in a
region of the brain called the precuneus, which is connected to two
inversely related brain networks: the dorsal attention network and the default
mode network. When one is active, the other is suppressed. The study discovered
that in cases of chronic tinnitus, the precuneus connects more to the first
network and less to the second. This may explain, among other things, why
patients remain more attentive to their tinnitus than necessary. These findings
provide objective evidence to guide more precise and effective future
treatments for tinnitus.
Jun 2017 (USA). Researchers at MIT developed a
non-invasive method for carrying out deep brain stimulation. This new
technique, called Temporal Interference, stimulates deep brain tissues
externally without the need for surgery. Although other methods like Transcranial
Magnetic Stimulation and Transcranial Direct Current Stimulation already exist,
these often activate both the targeted neurons and overlapping neurons,
potentially causing unwanted effects. In contrast, Temporal Interference
stimulates neurons more selectively. It uses frequencies above 1000 Hz, to
which neurons don’t respond. When two close frequencies (e.g., 2000 and 2010
Hz) are applied, they create a field with a frequency equal to their difference
(in this case, 10 Hz), which neurons can detect. This allows precise targeting
of specific brain regions, while surrounding areas only receive the higher
frequencies, which are outside the neuronal response range. This method, tested
on mice, is already being trialed in humans and may help treat conditions like
epilepsy, Alzheimer’s, PTSD, depression, and tinnitus.
Jun 2017 (Poland). During the 12th International
Tinnitus Seminar and 1st World Tinnitus Congress held in Warsaw, Poland, the COMIT’ID
study initiative was presented. It aims to integrate and bring together
tinnitus specialists from around the world to share their findings
collaboratively, allowing for comparison, contrast, and synthesis of results,
with patient voices also considered. Three key categories will be used to
classify proposed outcomes and treatments: sound-based therapies, psychological
therapies, and pharmacological treatments.
Apr 2017 (USA). Researchers at St. Jude Children’s
Research Hospital succeeded in regenerating immature hair cells in adult mice
by manipulating two genes (the p21 and Atoh1 proteins), which are known to play
a role in the regenerative process observed in fish and birds. This study, like
other similar ones (see below), opens the door to the development of methods
that could eventually be applied to humans, restoring hearing and potentially
addressing one of its most common consequences: tinnitus.
Feb 2017 (USA). A team from MIT, Brigham and Women’s
Hospital, and Massachusetts Eye and Ear discovered a drug combination capable
of regenerating hair cells in the inner ear. Through experiments on mice, they
found that this combination expanded the population of progenitor cells (also
known as supporting cells) and induced them to convert into hair cells. This
finding presents a potential pathway to treat hearing loss—which, in many
cases, is the root cause of tinnitus. (See also the Hearing Restoration Project,
Mar 2014).
Feb 2017 (USA). A team from Boston Children’s
Hospital and Harvard Medical School—who in 2015 had already achieved
rudimentary hearing restoration in genetically deaf mice through gene
therapy—managed this time to restore their hearing to a much higher level,
enabling them to hear even a whisper. They used a new viral vector called
Anc80L65 (a harmless virus) to deliver corrective genes into the cochlea’s hair
cells. Whereas earlier efforts had only reached the inner hair cells, this new
approach successfully targeted the harder-to-reach outer hair cells as well.
While its effectiveness in humans remains to be seen, this technique holds
promise for treating genetically-induced hearing loss, which could also relieve
associated tinnitus.
2016
Aug 2016 (USA). Researchers Glen Watson, Pei-Ciao
Tang, and Karen Smith from the University of Louisiana at Lafayette discovered
that a protein found in the hair cells of sea anemone tentacles—used to repair
damaged cells—showed promising results when applied to defective cells in mice.
They also found that rodents naturally produce a protein very similar to the
one found in sea anemones, which could potentially activate a similar repair
mechanism in mammals, including humans. Although this study was not focused on
tinnitus, any advancement in regenerating human hair cells could eventually
lead to a treatment for it.
Mar 2016 (USA). Drs. Thanos Tzounopoulos and Peter
Wipf from the University of Pittsburgh, along with a team of researchers,
succeeded in redesigning several components of Retigabine (an epilepsy drug) to
enhance its potency while reducing side effects. The new compound is called
RL648_81 (“RL-18”), and it is hoped that this compound may one day be used to
help treat tinnitus in humans. (See below for other related studies by Dr.
Tzounopoulos).
2015
Dec 2015 (USA). Dr. Fatima Husain and a team of
researchers at the University of Illinois found that the lesser degree of
disturbance caused by tinnitus in some people is due to the fact that they use
a different emotional processing pathway. Instead of using the amygdala, they
rely more on the frontal lobe, a region critical for attention, planning, and
impulse control. Based on this, the researchers suggested that increasing
activation in this brain area could help reduce the distress caused by
tinnitus—and one way to do so would be through physical activity.
Sep 2015 (United Kingdom). The company Autifony
Therapeutics was conducting Phase 2 of a clinical trial named CLARITY-1 to test
the drug AUT00063, which aims to regulate potassium channels. (See earlier
studies by Dr. Tzounopoulos regarding Retigabine.)
Oct 2015 (USA-Germany). Neuroscientists from
Georgetown University Medical Center (USA) and Technische Universität München
(Germany) found that three brain areas are involved in the generation of
tinnitus: the nucleus accumbens, the ventromedial prefrontal cortex, and the
anterior cingulate cortex. These areas act as a central system that controls or
limits perceptual sensations. They also found that this system relies on the
transmission of serotonin and dopamine between neurons, which opens up a
potential path to restore it using drugs that regulate these neurotransmitters.
(See earlier studies by Dr. Josef P. Rauschecker, who was also involved in this
research, regarding the connection between tinnitus and the ventromedial
prefrontal cortex.)
Jul 2015 (USA). Researchers at Oregon Health &
Science University and the VA Portland Medical Center found that Transcranial
Magnetic Stimulation (TMS) significantly improved tinnitus symptoms in more
than half of the participants in the largest clinical trial of its kind. The
results showed sustained relief (at least six months) for those participants.
These findings build on earlier studies exploring this type of stimulation (see
below under Neuromodulation / 2012–2013).
Jun 2015 (Japan). Researchers at Kyoto University
discovered that stem cell transplantation on the surface of the glial
scar—characteristic of neural damage—has the potential to restore the damaged
segment of the auditory nerve and thus restore hearing function, which could
help reduce or even eliminate tinnitus symptoms. These findings may also offer
a path to reduce hyperacusis symptoms. Dr. Marcelo Minolta (UK), with funding
from Action on Hearing Loss, is also conducting research using stem cells to
produce new hair cells and spiral ganglion neurons (which connect hair cells to
the brain), potentially reversing hearing loss.
Jun 2015 (USA). A new finding by Dr. Tzounopoulos and
neurophysiologist Anastasios Tzingounis from the University of Connecticut was
made public. It involved a drug named SF0034, which offered the same benefits
as Retigabine but with significantly fewer side effects when tested in animals.
Clinical trials are still needed to determine whether it is safe and effective
in humans. (See earlier studies on Retigabine led by Dr. Tzounopoulos.)
2014
Oct/Nov 2014 (USA). A pilot study conducted in 2014 by Dr. Jay F.
Piccirillo and his team at the Washington University School of Medicine in St.
Louis (USA), which focused on the N-methyl-D-aspartate (NMDA) receptor, found
that a computerized cognitive training program (designed to improve sound
processing, language, and memory) combined with the intake of the drug
D-cycloserine (a dextrorotatory form of the antibiotic cycloserine*) may help
reduce the distress caused by persistent tinnitus—not by eliminating its
perception, but by enhancing the brain’s ability to ignore it. As the study
involved a small sample of patients, a larger follow-up study is expected to
confirm the efficacy of this new approach.
Sep 2014 (USA). A research team in Boston led by Professor Daniel
Polley developed a sound-based game for use on a touchscreen tablet. The game
involves assembling a puzzle using mostly auditory cues instead of visual ones,
guiding users to find each piece. The ultimate goal is to reduce the volume of
tinnitus by rebalancing the overactive neural activity patterns in the brain
using sounds customized to the characteristics of each patient’s tinnitus.
Aug/Sep 2014 (Canada). Research led by Dr. Jordan Glicksman,
a resident investigator at the Schulich School of Medicine & Dentistry
(Ontario, Canada), has shown preliminary evidence that significant caffeine
consumption in women may be associated with a reduced risk of developing
tinnitus. Further studies are needed to confirm this relationship and determine
whether it could potentially lead to a treatment.
Aug 2014 (Australia). After ten years of research at Monash
University, the Australian company Small Technologies Cluster developed an iPod
app called tinAway — a sound therapy that uses multiple sound parameters
simultaneously to gradually reduce tinnitus intensity during daily sessions,
with the goal of achieving total suppression after a few weeks. This therapy is
based on the Auditory Scene Analysis model of chronic tinnitus. The
company is currently finalizing the prototype and preparing for clinical trials
and regulatory approval.
May 2014 (Argentina). A study led by Argentine researcher
Dr. Ana Belén Elgoyhen aimed to identify which areas and functions of the body
are targeted by drugs that produce tinnitus as a side effect — in other words,
to determine what biological targets these medications act on, and which of
them may be significant in tinnitus generation. The goal is to identify
compounds that can interfere with these interactions and potentially serve as
treatments.
May 2014 (Australia). Ongoing tinnitus research at the
University of Western Australia, led by scientist Helmy Mulders (Wilhelmina H.
A. M. Mulders), found that the drug Furosemide — a diuretic used to
treat hypertension — was able to reduce neural hyperactivity in the auditory
system in guinea pigs that had been induced to experience tinnitus. This
suggests that the drug may suppress the tinnitus signal. The next step will be
to conduct human trials to see whether the treatment can safely and effectively
reduce spontaneous hyperactivity in the auditory nerve caused by cochlear
damage, which is suspected to be a possible origin of tinnitus. If successful,
this approach could eliminate the need for severing the auditory nerve in
severe cases.
Mar 2014 (USA). The ongoing Hearing Restoration Project,
led by the Hearing Health Foundation in the United States, aims to discover a
method to stimulate regeneration of damaged inner ear cells in humans — just as
birds (such as chickens) and reptiles can naturally do. The goal is to
biologically restore hearing and potentially eliminate tinnitus. Related
studies are also being conducted by Dr. Andrew Groves and his team at the House
Ear Institute in California.
Mar 2014 (New Zealand). Researchers at the University of
Auckland are studying the effects of MDMA (also known as ecstasy), a
drug illegal in most countries, to see whether it can reduce tinnitus
perception when administered in controlled doses.
2013
Nov 2013 (USA). Another study focused on the Dorsal Cochlear
Nucleus (DCN), conducted by a research team at the University of Michigan
Medical School and led by Dr. Susan Shore, confirmed (in animal experiments)
that alterations in multisensory plasticity processes occurring in the DCN are
associated with tinnitus. In other words, an imbalance between the information
coming from the cochlea (in the ear) and that coming from the somatosensory
nerves in the neck and face could be the cause of tinnitus. Based on these
findings, Dr. Shore began developing a device that combines sound and
electrical stimulation targeting both the face and neck, with the aim of
restoring normal neuronal activity in the auditory pathways and thereby
reducing tinnitus symptoms in humans.
Oct 2013 (Sweden). Researchers at the Karolinska Institute also
discovered several years ago that with age, the hair cells in the ear lose
their functionality, their electric charge decreases, and as a result, they
become softer. The next step would be to investigate the proteins in these
cells in order to find a way to restore their rigidity.
Sep 2013 (Belgium). Belgian researcher Dr. Dirk De Ridder has also
suggested the possibility of finding a solution to tinnitus caused by hearing
loss by replicating the mechanism that occurs during sleep, in which most
patients no longer perceive their tinnitus. This mechanism may be related to
memory processing.
2009–2013 (Belgium–USA). Neuromodulation is another research approach being
explored. In general, it involves various brain stimulation methods, including
both electrical and magnetic techniques. One of the leading researchers in this
field is Dr. De Ridder, mentioned above.
2011
2011 (USA). In a study published in The Hearing Journal, it
was reported that scientists at the Stanford Initiative to Cure Hearing Loss
(SICHL) are exploring multiple paths to regenerate the inner ear. One of the
most promising lines of research involves reprogramming supporting cells to
become new hair cells, by activating a gene called Atoh1. Since hair cell
damage is one of the most common causes of hearing loss and tinnitus, these
efforts could lead to treatments that restore hearing and potentially eliminate
tinnitus.
2012
Oct 2012 (United Kingdom). A study by a team of scientists at Newcastle
University, led by Professor Tim Griffiths, seeks to better understand the
relationship between the auditory cortex, which processes sound, and the
amygdala (and the limbic system in general), which is involved in emotional
responses to unpleasant sounds.
2012 (Germany). Dr. Peter A. Tass, based on recent studies at the
Institute for Neuroscience and Medicine – Neuromodulation INM-7 at the Jülich
Research Center in Germany, proposed a technique called Coordinated Reset
Acoustic Neuromodulation. Instead of using electrical stimulation, it uses
sound stimulation via the emission of several tones of varying pitch. What
remains to be seen is its effectiveness.
2008
May 2008 (USA). Since fish have two ears like humans and also rely
on electrical activity for hearing, studies conducted over the past years on
the zebrafish have revealed that these fish are capable of regenerating damaged
or lost auditory cells — a process that appears to be promoted by the
administration of certain drugs that help restore electrical activity. If
similar results can be replicated in humans, this could offer hope for tinnitus
patients. Audiologist and cellular biologist Ernest J. Moore from Northwestern
University in Illinois initiated this line of research, and scientists at
Washington University have also conducted experiments with zebrafish to better
understand the mechanisms behind hearing loss.
Apr 2008 (UK, Brazil). Studies conducted by Brazilian scientists some
years ago showed that sacrocranial trigger point therapy was effective in some
patients with tinnitus resulting from head or neck trauma. Further
investigation would be needed to assess its efficacy in a broader group of
patients. On the other hand, British doctor and psychotherapist Julian Cowan
has developed a craniosacral therapy specifically aimed at treating tinnitus.
To conclude this review of
tinnitus-related research, it's worth mentioning that several researchers are
currently exploring how to make use of the tonotopic map in the auditory
cortex — a map in which neurons are organized according to the sound
frequencies to which they respond. The goal is to better understand how this
map is altered and to find a method to reset it, returning it to its normal
state — something that could help reduce tinnitus associated with those
tonotopic changes.
Footnotes:
* Cycloserine is an antibiotic that is sometimes considered an ototoxic substance that may cause tinnitus. However, in its D-form, it has been shown to enhance neuroplasticity and could therefore be beneficial in treating this auditory condition. In its D-form, has been explored for its effects on the NMDA receptor, which is implicated in neural plasticity and learning.
** Further developments in
this line of research were carried out in 2014 by Bramhall NF et al. and
Diensthuber M et al., and more recently (2015) by Stefan Heller and his team.
Also noteworthy is the 2015 study by Charles Askew and colleagues on genetic
therapies.
*** Some websites and internet forums suggest that Cannabis sativa (marijuana) might help alleviate tinnitus, though no reliable studies have confirmed this. While some individuals have reported relief, others have experienced worsening symptoms. MDMA has been under investigation for various therapeutic uses, including PTSD and anxiety. In this context, its potential to modulate perception may be relevant for tinnitus management.
**** Other drugs under investigation include D-methionine and OTO-311. In 2014, intratympanic injections of dexamethasone and methylprednisolone were also tested as potential treatments for idiopathic tinnitus (tinnitus of unknown origin). Glutamate-mediated excitotoxicity is a common mechanism in many neurological conditions and refers to nerve cell damage caused by overactivation of glutamate receptors.
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