Tag: hearing loss

A Natural Repair Process for Damaged Auditory Hair Cells

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Auditory researchers have discovered how hair cells can repair themselves after being damaged, an important insight could benefit efforts to develop new and better ways to treat and prevent hearing loss. Their findings are published in the free online journal eLife.

Found in the inner ear, hair cells derive their name from the hair-like structures that cover them and serve as mechanical antennas for sound detection. The prevailing belief is that when auditory hair cells are killed, they are gone for good. But this new research from University of Virginia School of Medicine shows that these delicate cells have the ability to repair themselves from damage caused by loud noises or other forms of stress.

“For many years, auditory research has placed considerable emphasis on the regeneration of sensory hair cells. Although these efforts continue, it is equally important to enhance our comprehension of the intrinsic mechanisms that govern the repair and maintenance of these cells. By gaining a deeper understanding of these inherent repair processes, we can uncover strategies to fortify them effectively. One such approach in the future might involve the utilisation of drugs that stimulate repair programs,” said researcher Jung-Bum Shin, PhD, of UVA’s Department of Neuroscience. “In essence, when replacement of hair cells proves challenging, the focus shifts towards repairing them instead. This dual strategy of regeneration and repair holds strong potential in advancing treatments for hearing loss and associated conditions.”

Repairing the damaged cells

In order to sense sound, hair cells are naturally fragile, but they also must withstand the continuous mechanical stress inherent in their jobs.

Prolonged exposure to loud noise harms hair cells in a variety of ways, and one of those is by damaging the cores of the “hairs” themselves. These hair-like structures are known as stereocilia, and Shin’s new research shows a process they use to repair themselves.

The hair cells do this by deploying a protein called XIRP2, which has the ability to sense damage to the cores, which are made of a substance called actin. Shin and his team found that XIRP2 first senses damage, then migrates to the damage site and repairs the cores by filling in new actin.

“We are especially excited to have identified a novel mechanism by which XIRP2 can sense damage-associated distortions of the actin backbone,” Shin said. “This is of relevance not only for hair cell research, but the broader cell biology discipline.”

The pioneering work has netted a grant to fund additional research into how the cores are repaired. By understanding this, scientists will be better positioned to develop new ways to battle hearing loss – even the kind that comes from aging, the researchers say.

“Age-related hearing loss affects at least a third of all older adults,” Shin said. “Understanding and harnessing internal mechanisms by which hair cells counteract wear and tear will be crucial in identifying ways to prevent age-related hearing loss. Furthermore, this knowledge holds potential implications for associated conditions such as Alzheimer’s disease and other dementia conditions.”

Source: University of Virginia Health System

Backdoor to the Inner Ear Allows Delivery of Gene Therapy

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An international team of researchers has developed a new method to deliver drugs into the inner ear, according to a new study in Science Translational Medicine. The discovery was possible by harnessing the natural flow of fluids in the brain and employing a little-understood backdoor into the cochlea. When combined to deliver a gene therapy that repairs inner ear hair cells, the researchers were able to restore hearing in deaf mice.

“These findings demonstrate that cerebrospinal fluid transport comprises an accessible route for gene delivery to the adult inner ear and may represent an important step towards using gene therapy to restore hearing in humans,” says lead author Barbara Canlon, professor at Karolinska Institutet.

The number of people worldwide predicted to have mild to complete hearing loss is expected to grow to around 2.5 billion by mid-century.  The primary cause is the death or loss of function of hair cells found in the cochlea – which relay sounds to the brain – due to mutations of critical genes, aging, noise exposure, and other factors. 

While hair cells do not naturally regenerate in humans and other mammals, gene therapies have shown promise and in separate studies have successfully repaired the function of hair cells in neo-natal and very young mice.

“However, as both mice and humans age, the cochlea, already a delicate structure, becomes enclosed in the temporal bone. At this point, any effort to reach the cochlea and deliver gene therapy via surgery risks damaging this sensitive area and altering hearing,” says Barbara Canlon.

In the new study, the researchers describe a little-understood passage into the cochlea called the cochlear aqueduct. The cochlear aqueduct is a thin boney channel no larger than several strands of hair. 

Channel for spinal fluid

A new study shows that the cochlear aqueduct acts as a conduit between the cerebrospinal fluid found in the inner ear and the rest of the brain. 

Scientists are developing a clearer picture of the mechanics of the glymphatic system, the brain’s unique process of removing waste. Because the glymphatic system pumps cerebrospinal fluid deep into brain tissue to wash away toxic proteins, researchers have been eyeing it as a potential new way to deliver drugs into the brain, a major challenge in developing drugs for neurological disorders. 

The new study represented an opportunity to put the drug delivery potential of the glymphatic system to the test, while at the same time targeting a previously unreachable part of the auditory system.   

Employing several imagining and modeling technologies, the researchers were able to develop a detailed portrait of how fluid from other parts of the brain flows through the cochlear aqueduct and into the inner ear.

The team then injected an adeno-associated virus into the cisterna magna, a large reservoir of cerebrospinal fluid found at the base of the skull. 

The virus found its way into the inner ear via the cochlear aqueduct and delivered a gene therapy that expresses a protein called vesicular glutamate transporter-3, which enables the hair cells to transmit signals and rescue hearing in adult deaf mice. 

“This new delivery route into the ear may not only serve the advancement of auditory research but also prove useful when translated to humans with progressive genetic-mediated hearing loss,” says Barbara Canlon.

Source: Karolinska Institutet

Possible Explanation for Why More Men Develop Hearing Loss in Old Age

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A new study led by Yale School of Medicine scientists and published in BMC has pinpointed why some adults – by some estimates, at least 50% of the population after 75 years of age – develop hearing problems.

While congenital hearing impairment – usually presenting in childhood – result from rare mutations, hearing problems in adults are likely due to the cumulative effect of polygenic risk and environmental factors.

Recent genome-wide association studies have uncovered several risk genes that are implicated in hearing problems in adults, however some factors still have not adequately been investigated by large-scale genetic studies.

For instance, there is limited information about why hearing problems among older adults are more common, more severe, and with earlier onset in men than in women. It is uncertain how hearing-related polygenic risk translates among people of diverse ancestral backgrounds.

While environmental risk factors such as noise exposure and tobacco smoking are known to increase the risk of hearing problems, the molecular mechanisms underlying these associations are unclear.

Researchers sampled nearly 750 000 adults and identified 54 risk variants – including 12 novel variants – that could contribute to hearing problems. They also highlighted how hormonal regulation may play a role in the differences between hearing problems in men and women.

Analysing multiple ancestry groups, the researchers demonstrated that polygenic risk in hearing problems is shared across human populations. They also determined genes involved in brain development interact with sex, noise pollution, and tobacco smoking in relation to their associations with hearing problems.

“Our results support that large-scale genetic studies are useful instruments to understand the biology and the epidemiology of hearing problems in adults,” said Renato Polimanti, PhD, associate professor of psychiatry at Yale School of Medicine and senior author of the study.

Overall, the findings contribute to identifying possible molecular targets for drug development and define novel strategies to identify older adults at risk of losing their hearing.

The study could lead to changes in how older adults with hearing problems are assessed and treated. Hearing loss can impair communications, and that can result in social isolation with major health, psychosocial, and economic consequences, reducing the quality of life of those affected.

Source: Yale University

Can Progressive Hearing Loss be Reversed?

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In humans, hearing loss from exposure to loud noises is progressive because the primary cells which detect sound, cochlear hair cells, cannot regenerate if damaged or lost. People who have repeated exposure to loud noises, like military personnel, construction workers, and musicians, are most at risk for this type of hearing loss, though it can happen to anyone over time.

On the other hand, birds and fish can regenerate these hair cells, and now researchers report their advances in promoting this effect in mammals. Their work is published in Frontiers in Cellular Neuroscience.

“We know from our previous work that expression of an active growth gene, called ERBB2, was able to activate the growth of new hair cells (in mammals), but we didn’t fully understand why,” said Patricia White, PhD, professor of Neuroscience and Otolaryngology at the University of Rochester Medical Center. The 2018 study led by Jingyuan Zhang, PhD, a postdoctoral fellow in the White lab at the time, found that activating the growth gene ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to multiply and activate other neighbouring stem cells to become new sensory hair cells.

“This new study tells us how that activation is happening – a significant advance toward the ultimate goal of generating new cochlear hair cells in mammals,” said White.

Using single-cell RNA sequencing in mice, researchers compared cells with an overactive growth gene (ERBB2 signalling) with similar cells that lacked such signalling. They found the growth gene, ERBB2, promoted stem cell-like development by initiating the expression of multiple proteins – including SPP1, a protein that signals through the CD44 receptor. The CD44 receptor is known to be present in cochlear-supporting cells. This increase in cellular response promoted mitosis in the supporting cells, a key event for regeneration.

“When we checked this process in adult mice, we were able to show that ERBB2 expression drove the protein expression of SPP1 that is necessary to activate CD44 and grow new hair cells,” said Dorota Piekna-Przybylska, PhD, a staff scientist in the White Lab and first author of the study. “This discovery has made it clear that regeneration is not only restricted to the early stages of development. We believe we can use these findings to drive regeneration in adults.”

“We plan to further investigation of this phenomenon from a mechanistic perspective to determine whether it can improve auditory function after damage in mammals. That is the ultimate goal,” said White.

Source: University of Rochester Medical Center

Hearing Loss Linked to Dementia Risk

A nationally representative study published in JAMA found that older adults with greater severity of hearing loss were more likely to have dementia, but the likelihood of dementia was lower among hearing aid users compared to non-users.

The findings are consistent with prior studies showing that hearing loss might be a contributing factor to dementia risk over time, and that treating hearing loss may lower dementia risk.

“This study refines what we’ve observed about the link between hearing loss and dementia, and builds support for public health action to improve hearing care access,” says lead author Alison Huang, PhD, MPH, a senior research associate in the Bloomberg School’s Department of Epidemiology and at the Cochlear Center for Hearing and Public Health, also at the Bloomberg School.

Hearing loss is a critical public health issue affecting two-thirds of Americans over 70. The growing understanding that hearing loss might be linked to the risk of dementia, which impacts millions, and other adverse outcomes has called attention to implementing possible strategies to treat hearing loss.

For the new study, Huang and colleagues analysed a nationally representative dataset from the National Health and Aging Trends Study (NHATS). Funded by the National Institute on Aging, the NHATS has been ongoing since 2011, and uses a nationwide sample of Medicare beneficiaries over age 65, with a focus on the 90-and-over group as well as Black individuals.

The analysis covered 2413 individuals, about half of whom were over 80 and showed a clear association between severity of hearing loss and dementia. Prevalence of dementia among the participants with moderate/severe hearing loss was 61% higher than prevalence among participants who had normal hearing. Hearing aid use was associated with a 32% lower prevalence of dementia in the 853 participants who had moderate/severe hearing loss.

The authors note that many past studies were limited in that they relied on in-clinic data collection, leaving out vulnerable populations that did not have the means or capacity to get to a clinic. For their study, the researchers collected data from participants through in-home testing and interviews.

How hearing loss is linked to dementia isn’t yet clear, and studies point to several possible mechanisms. Huang’s research adds to a body of work by the Cochlear Center for Hearing and Public Health examining the relationship between hearing loss and dementia.

Source: Johns Hopkins Bloomberg School of Public Health

Hearing Loss in Older People Can be Prevented While Young

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Based on a new model, researchers have proposed a way to prevent hearing loss in older people by addressing socioeconomic inequalities encountered while young.

The model developed by University of Manchester researchers could have an impact on the estimated 466 million people worldwide with disabling hearing loss, which mostly affects the elderly.

Published in Trends in Hearing, this is the first study examining the mechanisms and explaining the relationship between a lifetime of socioeconomic inequalities and hearing health.

Previous studies have shown that people with hearing loss are more likely to have poorer educational achievement, higher rates of unemployment and lower annual family income compared to those with other health conditions.

They are also more likely to have long-term health conditions and a higher overall disease burden than older people without hearing loss.

Lead researcher Dr Dalia Tsimpida said: “Hearing deterioration is a lifelong process but not an inevitable result of aging. Understanding this process is an essential step in addressing the global burden of hearing loss.”

Dr Tsimpida, a postdoctoral researcher at the University’s Institute for Health Policy and Organization (IHPO), added: “The key determinants of poor hearing health in the course of a life and their interdependency as described by this model is a powerful way to intervene in this major problem.

“Our focus is not simply on the age of older adults but on factors which impact on people earlier in life, which if modified could reduce hearing loss in older age.”

“This approach in hearing health can lead to the development of appropriate interventions and public health strategies that can have significant health policy and practice implications.”

Study co-author Dr Maria Panagioti said: “This model provides now a visual representation of the several modifiable factors of hearing loss in distinct life stages and their evolution over time, which is new thinking in hearing loss research.

“Given the burden of adult-onset hearing loss, such a conceptual tool for hearing health inequalities has the potential of improving the physical, mental and social wellbeing of individuals.”

Source: Medical Xpress

Journal information: Dialechti Tsimpida et al, Conceptual Model of Hearing Health Inequalities (HHI Model): A Critical Interpretive Synthesis, Trends in Hearing (2021). DOI: 10.1177/23312165211002963