Here is a picture of my mom with her hearing aid in. You can just make out the wire that is going into her ear canal. While the hearing aid is hard to see, my very observant 6-yr old (at the time) niece told my mother, “you put your earrings on wrong today” when she first saw the aids.

This morning I read about a new potential treatment for hearing loss, one that could be very exciting. Marlon Aguilar, the incredibly talented sound engineer for our MOOC, sent me the link to a news story, reporting a test of a minimally invasive treatment for hearing loss. Currently we “treat” most hearing loss by providing hearing aids which does not treat the hearing loss at all but rather provides a loud speaker to the ear. The novel treatment being tested gets closer to the real problem in age-related hearing loss, viz the death of hair cells.

Hair cells are the sensory cells of the inner ear. In the cochlea, hair cells are sensitive to sound waves and in the vestibulum, hair cells are sensitive to accelerating forces caused by head movements or gravity. Hair cells are not neurons but they sure are neuro-pals. They derive from the same layer of embryonic tissue as do neurons (ectoderm). And they share many properties with neurons. For example, they use electrical signaling and they release neurotransmitter onto auditory nerve fibers (true neurons). One way to think about this is to consider hair cells as cousins of neurons that have grown up in a different country and speak a different but related language. So my cousins who were born in France are my second (I think) cousins regardless of the fact that they’ve lived their lives in France and speak French as their native tongue. To stretch this analogy, whether hair cells are Americans or French is of little import with regard to hearing which simply does not work, not even a little bit, without hair cells.

In mammals, hair cells resemble neurons in that they don’t regenerate. Once they die, that is it. And this finality is the problem for most people who suffer a loss of hearing during life. Most commonly, very loud (>100-120 dB, being 10 feet away from a jackhammer or jet engine) noises or simply repeated exposure to loud (70-120 dB, includes the sound levels in most public places these days). Check out this terrific piece by NYT reporter Cara Buckley on the sound levels present in modern life.

For all of you wondering about earbuds, a good rule of thumb is that if the sound can be heard by someone else besides the person wearing the earbuds, the volume is too loud and hair cells are probably being damaged. The damage caused is not likely to manifest as an immediate problem but it is likely to start hair cells on the road to a death that will happen sooner rather than later.

The upshot is that virtually all of us are exposed, whether we like it or not and whether we intentionally seek out loud environments or not, to much higher levels of sound than our ears evolved to withstand, a problem that is exacerbated by our increasingly long lifespans. As I walk from my train to my laboratory every day, I feel helpless as my poor vulnerable hair cells are assaulted first by the train horn and track sounds, then by cars, construction sounds, and the do-we-really-need-it beeping of backing up trucks.

The exposure to moderate and loud sounds is responsible for most people’s hearing loss later in life. Note that Tom Rice, featured in a previous post, lost his hearing apparently because of some genetic condition and is not typical of most people with late-in-life hearing loss. My 86-year old mother is typical; she has been hard of hearing for 15 years or so and has worn hearing aids for 12 years or so. For a great description of life with hearing loss, read Barbara Stenross’s memoir, Missed Connections.

Let’s return to hair cells. As I said, hair cells do not regenerate in mammals. But they do in other animals!! That is exciting because if hair cells regenerate in other animals, it may be possible to manipulate the mammalian cochlea into jumping on that same road to regeneration. Essentially, the fact that the hair cells of fish, reptiles and birds can and do regenerate suggests that somehow, there exists a path by which mammalian hair cells could also regenerate. So how does hair cell regeneration happen in a bird, for example? Well the first thing is that supporting cells (these are the support staff for hair cells, akin to glia for neurons) proliferate – that means they divide alot and thereby make lots of new cells. Some of these new cells then differentiate, meaning they go from being a general cell to a cell that will be either another supporting cell or – drum roll, please – a hair cell.

As it turns out, there is a gene called Atoh1 which codes for a protein that is a transcriptional factor (meaning it modifies which genes are read out and made into RNA and ultimately into protein).

Atoh1 is a mammalian gene. It is a homolog of a gene in the fruit fly called atonal. That means that one ancestral gene evolved into atonal in flies and into Atoh1 in mammals. Put another way, atonal and Atoh1 evolved from a common  gene so that while they differ in some bits of sequence, they share basic sequence structure. Essentially, the two genes share a great-great x some-large-number grandparent.

Atoh1 is necessary and sufficient to turn proliferating supporting cells into hair cells and it does so in birds and other non-mammals. What’s the problem in mammals? Well there is no Atoh1 around. Supporting cells in the adult inner ear don’t make (express) Atoh1. Now finally we are ready to get to this week’s exciting news. Hinrich Staecker and colleagues at the University of Kansas Medical Center are planning on providing Atoh1 to people with hearing loss, by infecting ears with (non-replicating and therefore harmless) viruses that contain the Atoh1 gene. The hope is that just as Staecker found in experiments on hard-of-hearing mice, supporting cells in the cochlea of hard-of-hearing humans will incorporate the Atoh1 gene into their own DNA and start making the protein, enabling hair cells to be born and hearing to improve.

Much of the background information for this post came from a terrific review article by Andrew K. Groves, Kaidi D. Zhang, and Donna M. Fekete, entitled The Genetics of Hair Cell Development and Regeneration, and published in the Annual Reviews of Neuroscience (2013. 36:361–81). Unfortunately, this paper is not available at the click of a button. I can get to it because my university has a paid subscription to the journal. Unless you also have access, typically through an institution of higher learning, articles published in non-open access journals are not freely and easily available. This may appear to be a one-sided issue but it is not. But I digress; let’s talk about open access another time.

This is really exciting. There is the potential to help people that have lost cochlear hair cells due to either noise (see above) or drugs such as some  antibiotics and chemotherepeutics. Less common but also life-impacting is the loss of vestibular hair cells, again usually due to ototoxicity (or ear-toxicity) of some drugs. The viral introduction of Atoh1 could also potentially help individuals with a loss of vestibular hair cells.

Is viral Atoh1 the answer to all hearing loss? Absolutely not but, if it works, it could help the plurality of hard-of-hearing older people. You may think that most older people with hearing loss, including my mom, are doing okay. Indeed you can barely see hearing aids these days. However, hearing aids are not a cure, far from it. Hearing aids are megaphones that amplify incoming sound to a very handicapped cochlea with hair cells that respond to the frequencies at and around the amplified frequencies. Outer hair cells, in contrast, provide amplification that is restricted to the frequency that is present in the incoming sound. Bottom line, hearing will not be normal even with top of the line hearing aids, because there are no hair cells to do their magic. The possibility of regenerating hair cells changes the game. Exciting!