How regrowing tiny hairs could restore hearing loss

Man getting fitted with hearing aids

Hearing loss is something that affect tens of millions of Americans. Usually people notice those changes as they get older but the damage can be done years before that through the use of some prescription drugs or exposure to loud noise (I knew I shouldn’t have sat in the 6th row of that Led Zeppelin concert!)

Now researchers at the University of Southern California (USC) have identified the mechanism that appears to stop cells that are crucial to hearing from regenerating.

In a news release Dr. Neil Segil says this could, in theory, help reverse some hearing loss.  “Permanent hearing loss affects more than 60 percent of the population that reaches retirement age. Our study suggests new gene engineering approaches that could be used to channel some of the same regenerative capability present in embryonic inner ear cells.”

The inner ear has two types of cells that are crucial for hearing; “hair cells” are sensory receptors and these help the brain detect sounds, and support cells that play, as the name implies, an important structural and supporting role for the hair cells.

In people, once the hair cells are damaged that’s it, you can’t repair or replace them and the resulting hearing loss is permanent. But mice, in the first few days of life, have ability to turn some of their support cells into hair cells, thus repairing any damage. So Segil and the team set out to identify how mice were able to do that and see if those lessons could be applied to people.

They identified specific proteins that played a key role in turning genes on and off, regulating if and when the support cells could turn into hair cells. They found that one molecule, H3K4mel, was particularly important in activating the correct genetic changes need to turn the support cells into hair cells. But in mice, levels of H3K4mel disappeared quickly after birth, so the team found a drug that helped preserve the molecule, meaning the support cells retained the ability to turn into hair cells.

Now, obviously because this was just done in mice there’s a lot more work that needs to be done to see if it can also work in people, but Segil says it’s certainly an encouraging and intriguing start.

“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing. Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart.”

The study is published in the journal Developmental Cell

CIRM has funded several projects targeting hearing loss. You can find them here.

Persistence pays off in search for clue to heart defects

A team of scientists led by Benoit Bruneau (left), including Irfan Kathiriya (center) and Kavitha Rao (right), make inroads into understanding what genes are improperly deployed in some cases of congenital heart disease.  Photo courtesy Gladstone Institute

For more than 20 years Dr. Benoit Bruneau has been trying to identify the causes of congenital heart disease, the most common form of birth defect in the U.S. It turns out that it’s not one cause, but many.

Congenital heart disease covers a broad range of defects, some relatively minor and others life-threatening and even fatal. It’s been known that a mutation in a gene called TBX5 is responsible for some of these defects, so, in a CIRM-funded study ($1.56 million), Bruneau zeroed in on this mutation to see if it could help provide some answers.

In the past Bruneau, the director of the Gladstone Institute of Cardiovascular Disease, had worked with a mouse model of TBX5, but this time he used human induced pluripotent stem cells (iPSCs). These are cells that can be manipulated in the lab to become any kind of cell in the human body. In a news release Bruneau says this was an important step forward.

“This is really the first time we’ve been able to study this genetic mutation in a human context. The mouse heart is a good proxy for the human heart, but it’s not exactly the same, so it’s important to be able to carry out these experiments in human cells.”

The team took some iPSCs, changed them into heart cells, and used a gene editing tool called CRISPR-Cas9 to create the kinds of mutations in TBX5 that are seen in people with congenital heart disease. What they found was some genes were affected a lot, some not so much. Which is what you might expect in a condition that causes so many different forms of problems.

“It makes sense that some are more affected than others, but this is the first experimental data in human cells to show that diversity,” says Bruneau.

But they didn’t stop there. Oh no. Then they did a deep dive analysis to understand how the different ways that different cells were impacted related to each other. They found some cells were directly affected by the TBX5 mutation but others were indirectly affected.

The study doesn’t point to a simple way of treating congenital heart disease but Bruneau says it does give us a much better understanding of what’s going wrong, and perhaps will give us better ideas on how to stop that.

“Our new data reveal that the genes are really all part of one network—complex but singular—which needs to stay balanced during heart development. That means if we can figure out a balancing factor that keeps this network functioning, we might be able to help prevent congenital heart defects.”

The study is published in the journal Developmental Cell.