Posts Tagged ‘hearing loss’

It’s well known that exposure to extremely loud noises — whether it’s an explosion, a firecracker or even a concert — can lead to permanent hearing loss.
But knowing how to treat noise-induced hearing loss, which affects about 15 percent of Americans, has largely remained a mystery. That may eventually change, thanks to new research from the Keck School of Medicine of USC, which sheds light on how noise-induced hearing loss happens and shows how a simple injection of a salt- or sugar-based solution into the middle ear may preserve hearing. The results of the study were published today in PNAS.

Deafening sound
To develop a treatment for noise-induced hearing loss, the researchers first had to understand its mechanisms. They built a tool using novel miniature optics to image inside the cochlea, the hearing portion of the inner ear, and exposed mice to a loud noise similar to that of a roadside bomb.

They discovered that two things happen after exposure to a loud noise: sensory hair cells, which are the cells that detect sound and convert it to neural signals, die, and the inner ear fills with excess fluid, leading to the death of neurons.

“That buildup of fluid pressure in the inner ear is something you might notice if you go to a loud concert,” says the study’s corresponding author John Oghalai, MD, chair and professor of the USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery and holder of the Leon J. Tiber and David S. Alpert Chair in Medicine. “When you leave the concert, your ears might feel full and you might have ringing in your ears. We were able to see that this buildup of fluid correlates with neuron loss.”

Both neurons and sensory hair cells play critical roles in hearing.

“The death of sensory hair cells leads to hearing loss. But even if some sensory hair cells remain and still work, if they’re not connected to a neuron, then the brain won’t hear the sound,” Oghalai says.

The researchers found that sensory hair cell death occurred immediately after exposure to loud noise and was irreversible. Neuron damage, however, had a delayed onset, opening a window of opportunity for treatment.

A simple solution

The buildup of fluid in the inner ear occurred over a period of a few hours after loud noise exposure and contained high concentrations of potassium. To reverse the effects of the potassium and reduce the fluid buildup, salt- and sugar-based solutions were injected into the middle ear, just through the eardrum, three hours after noise exposure. The researchers found that treatment with these solutions prevented 45–64 percent of neuron loss, suggesting that the treatment may offer a way to preserve hearing function.

The treatment could have several potential applications, Oghalai explains.

“I can envision soldiers carrying a small bottle of this solution with them and using it to prevent hearing damage after exposure to blast pressure from a roadside bomb,” he says. “It might also have potential as a treatment for other diseases of the inner ear that are associated with fluid buildup, such as Meniere’s disease.”

Oghalai and his team plan to conduct further research on the exact sequence of steps between fluid buildup in the inner ear and neuron death, followed by clinical trials of their potential treatment for noise-induced hearing loss.

https://www.keckmedicine.org/a-simple-treatment-may-minimize-hearing-loss-triggered-by-loud-noises/

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Researchers from St. Jude Children’s Research Hospital have discovered that inhibiting an enzyme called cyclin-dependent kinase 2 (CDK2) protects mice and rats from noise- or drug-induced hearing loss. The study, which will be published March 7 in the Journal of Experimental Medicine, suggests that CDK2 inhibitors prevent the death of inner ear cells, which has the potential to save the hearing of millions of people around the world.

According to the World Health Organization, 360 million people worldwide, including 32 million children, suffer from hearing loss caused by congenital defects or other factors. These factors include infectious disease, use of certain medicines, or exposure to excessive noise. Yet, there are currently no FDA-approved drugs to prevent or treat hearing loss.

A team of researchers led by Dr. Jian Zuo screened over 4,000 drugs for their ability to protect cochlear cells from the chemotherapy agent cisplatin. Cisplatin is used to treat a variety of cancers but causes irreversible hearing loss in up to 70% of patients.

Zuo and colleagues identified multiple compounds that protected cochlear cells from cisplatin, several of which are already approved to treat other conditions. Three of the ten most effective compounds were inhibitors of an enzyme called CDK2. One of these CDK2 inhibitors, kenpaullone, was more effective than four other compounds that are currently in clinical trials for treating hearing loss.

Injecting kenpaullone into the middle ear protected both mice and rats from cisplatin-induced hearing loss. Moreover, kenpaullone also protected the hearing of mice to noise as loud as 100 dB. “Given that 100-dB noise is in the range of noise insults commonly experienced by people in our society, kenpaullone could have significant clinical application in treating noise-induced hearing loss,” says Zuo.

In the case of cisplatin-induced hearing loss, kenpaullone appears to protect hair cells by preventing CDK2 from stimulating the production of toxic reactive oxygen species from the cells’ mitochondria.

“The robust protection conferred by one-time local delivery of kenpaullone suggests that CDK2 inhibitors may transform the clinical prevention and treatment of cisplatin- and noise-induced hearing loss in patients,” Zuo says. “Modifications of the treatment regimens, additional optimization of the delivery methods via the use of hydrogels, and structural modifications of the compounds via medicinal chemistry could ensure even better results with CDK2 inhibitors in treating hearing loss in humans.”

https://www.technologynetworks.com/drug-discovery/news/new-drug-compounds-help-prevent-hearing-loss-298358?utm_campaign=Newsletter_TN_BreakingScienceNews&utm_source=hs_email&utm_medium=email&utm_content=61208436&_hsenc=p2ANqtz-9wXzuHgjTCBE-kfjy2aI1t3MUL9sd_5yCjnzo0oJb_R1HQdkMueXmiVXpB290Xv_tYEY8WdZxoDvtPtxyl3ajVpcPK1Q&_hsmi=61208436