Stem Cell Therapy will help hearing loss.

Hearing loss and stem cell therapy.

Source : The Scientist Sep, 2015

It increased life expectancy worldwide. And many researchers are continuing to study slow down the aging body organs. However, not much research about aging are hearing so far. Since most trouble-hearing people have relied on a method using a hearing aid.
Many people have a resistance for the use of hearing aids. This has also psychological factors. If they are using a hearing aid, I think he can be seen as a very old man. And it should be rejected. If this method can be treated by the method of machine use or implantation is not invisible, people want the treatment is expected to increase.

For decades, the only remedies for hearing loss were devices such as hearing aids or cochlear implants.
Now, the first pharmaceutical treatments may be on the way. Stem cell therapy is also in that way.

An associate professor at Oregon Health & Science University (OHSU) in Portland, Brigande works to identify genes involved in development of the mammalian inner ear and to prevent congenital genetic hearing loss by reprogramming cells during embryonic development in mouse models of human hearing loss. He feels that his experiences give him a deeper connection to the disorders he hopes to treat. He lives the life of the patient.


Unfortunately, while the hearing field has made great strides over the last several decades in understanding the biology of the inner ear and the causes of hearing loss, there are still no approved drugs to treat the condition. Rather, the 360 million people worldwide who suffer disabling hearing loss rely on imperfect devices in order to hear. For example, Brigande uses a hearing aid in his right ear paired with microphones that deliver sound straight to the device. But hearing aids can be tough to tune, sometimes emit painfully loud sounds, and only work for those patients who retain at least some functional hair cells봳he sensory cells of the ear that translate sound into nerve impulses.

The other main option, the cochlear implant, bypasses the inner-ear hair cells by directly exciting the neurons that carry auditory signals to the brain. Cochlear implants have accomplished the remarkable feat of allowing deaf people to understand human speech and more confidently navigate their environments. But patients with cochlear implants attest that the experience is unlike natural hearing, consisting of buzzing or staticky sounds. And for some, as was the case for Brigande셲 left ear, a cochlear implant may not work at all, perhaps because of auditory nerve deterioration that can occur after years without stimulation.

However, better solutions may be on the horizon.

Researchers are now using their knowledge of the ear셲 biology to develop drugs and therapies that could rebuild hair cells and even, someday, auditory nerves. This is based on regenerative medicine.

There셲 much deeper knowledge of the genes that are important or even required to specify sensory hair cell identity and cochlear function. Other groups are working to protect the inner ear셲 delicate cells from damage before hearing begins to wane.
While many of these therapies are still at the earliest stages of development, clinical testing is underway for at least half a dozen small-molecule and gene therapies that may prevent hearing loss or even reverse it to some degree. And more than a dozen small biotechs, along with pharma giants such as Novartis, Eli Lilly, and Pfizer, are now active in the area.

Staving off hearing loss

Some researchers are working toward full regeneration of hearing organs, but a near-term goal is the prevention of damage in the first place. It is, after all, easier to preserve the cells of the inner ear than to re-create them.
Switzerland-based biotech Auris Medical is preparing for two Phase 3 clinical trials that will test a drug called AM-111 for the treatment of sudden hearing loss within three days of its onset.

Meanwhile, a recent Phase 3 trial by North Carolina밷ased Fennec Pharmaceuticals indicated that sodium thiosulfate can safely and successfully neutralize harmful metabolites of cisplatin, to prevent loss of hair cells and cochlear neurons in young cancer patients being treated with the chemotherapeutic agent. The company is now running a second Phase 3 trial.

And at Sound Pharmaceuticals in Seattle, Washington, researchers are eyeing yet another step on the pathway to hair-cell damage: attack by reactive oxygen species during times of stress. Different forms of the small molecule ebselen are in Phase 2 clinical development for protection of hearing in people at risk of exposure to loud noises, as well as for patients receiving cisplatin or related chemotherapeutic agents.

Repairing hair cells

For patients whose hearing loss is already underway, researchers are tackling the more difficult task of fixing damaged or deficient hair cells. One group, led by Jeffrey Holt of Boston Children Hospital and Harvard Medical School, reported in July on a gene therapy that can restore hearing in mice that are deficient in the gene Tmc1. The precise function of TMC1 remains unclear. Animals lacking the gene have intact hair cells and yet cannot hear, likely because the ion channels that propagate the signal are nonfunctional. The researchers hope to eventually test this gene therapy in people with genetic hearing loss caused by mutations to TMC1.

Others are working to rebuild hair cells entirely. In 1988, hearing scientists Ed Rubel of the University of Washington and Brenda Ryals, now at James Madison University in Harrisonburg, Virginia, discovered that adult birds can regrow their inner-ear hair cells following damage. This was the first time any adult vertebrate had been shown to regenerate hair cells after damage, but it soon became clear that many nonmammalian species regenerate hair cells, either directly converting supporting cells of the inner ear into sensory hair cells or generating hair cells as supporting cells divide.

Even if human hair cells can be regenerated, however, it remains to be seen how much hearing might return. Regenerated hair cells would need to grow delicate stereocilia to respond to sound and may only be functional if they arrange themselves in a precise configuration within the cochlea and properly connect to the auditory neurons. Moreover, the mass of the regenerated cells could affect how the inner ear vibrates in response to sound. 쏷he cochlea may be sufficiently precise that adding in a couple of new hair cells would screw things up, says HRP head Peter Barr-Gillespie, who studies mechanotransduction by hair cells at OHSU. 쏻e shouldn셳 expect a magic treatment that immediately restores everything to high fidelit. It will be stepwise.

Beyond hair cells

Scientists once assumed that loud noises primarily damage hair cells. But in 2009, Charles Liberman and Sharon Kujawa at Harvard Medical School and Massachusetts Eye and Ear Infirmary demonstrated that mice exposed to two hours of intense, highpitched sound can suffer damage to the synapses that link hair cells in the inner ear with the spiral ganglion neurons that relay the signal to the brain. Specifically, the tips of the spiral ganglion neurons degenerate following exposure to loud noise, possibly as a result of excitotoxicity, a process by which nerve cells are poisoned by excess exposure to the neurotransmitter glutamate. This degeneration can translate to hearing loss even in the absence of damage to the hair cells themselves.

On the bright side, it appears that the spiral ganglion neurons often retain their cell bodies and their processes projecting to the brain, suggesting that all it would take to restore hearing in that case would be to close the less-than-1-millimeter gap between the hair cells and neurons. Last year, Liberman and his colleagues achieved just that in mice by boosting levels of a protein called neurotrophin-3 (Ntf-3), which stimulates and guides neuronal growth.
If neurotrophins could restore synapses to millions of elderly people with agerelated hearing loss? If a lot of people are walking around with reasonable hair cell populations but half their neurons are gone, and if you could partially or totally reverse that, that would be huge. Hearing loss may also have roots beyond the ear entirely, in the auditory processing regions of the brain.

U.K.-based biotech Autifony Therapeutics aims to treat age-related hearing loss with an oral drug that crosses the blood-brain barrier and modulates the firing of neurons deep in the auditory cortex and other brain regions in the auditory pathway.


NERVE REGENERATION: Experimentally deafened mammals suffer loss of sensory hair cells followed by atrophy of the cochlear nerve. But a new therapy being tested in guinea pigs may spur the regeneration of the nerve (left, green projections), by placing an implant in the cochlea that can mediate the uptake of a gene therapy construct encoding brain-derived neurotrophic factor (BDNF). IMAGE BY JEREMY PINYON AND GARY HOUSLEY UNSW AUSTRALIA.


Hearing the future

The final frontier of restoring lost hearing is stem cell therapy.
Researchers hope to differentiate stem cells into new hair cells and spiral ganglion neurons and implant them in the inner ear, replacing damaged or degenerated cells. While many therapies are geared towards regenerating structures in the recently deafened, stem cell therapy could theoretically help people who never developed proper inner ear structures at all, or whose cells are completely degenerated. 쏞onceptually, you could rebuild the whole organ, if you have the technology, says Marcelo Rivolta, who studies stem cell therapies at the University of Sheffield in the U.K. Rivolta셲 lab began by studying stem cells collected from the inner ears of human fetuses, unraveling which pathways direct the differentiation of auditory neurons and hair cells. Using this knowledge, the team has successfully differentiated human embryonic stem cells (hESCs) into hair cells and spiral ganglion neurons. Transplanting hESC-derived inner ear밹ell progenitors into gerbils with degenerated auditory nerves, the researchers found that the cells differentiated and took root in the animals, which showed improved sensitivity to sound. It will be a few years at least before Rivolta and other groups working on cellular approaches to hearing loss will test such therapies in humans, however.

For people with hearing loss, we expect the development of various therapeutic agents. We’re waiting that Stem Cell Therapy will help hearing loss.

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