Researchers identify drug that protects mice and rats against hearing loss

Kenpaullone was shown to be more effective than other compounds currently being investigated in clinical trials.

360 million people worldwide suffer from hearing loss according to the World Health Organization. Yet, there are no FDA-approved drugs to prevent or treat it. In this study, Jian Zuo and his team report new compounds they are hopeful will put an end to hearing loss.

ResearchGate: What motivated you to conduct this study?  

Jian Zuo: We have been working on this topic for almost five years together with various labs and departments at St. Jude Children’s Research Hospital. Initially, we were interested in preventing or repairing hearing loss associated among chemotherapy among cancer patients. After publishing a study a few years ago that looked at the genetic component of hearing loss in brain tumor patients, we thought we could develop drugs to help patients that are prone to hearing loss.

We took advantage of the huge amount of resources that St. Jude had available for drug screenings. We screened over 4000 compounds and identified the top ten. From these top ten compounds, we then characterized the top compound, which is kenpaullone. We found it to be very protective in mouse and rat models.

The mechanism works by inhibiting an enzyme called cyclin-dependent kinase 2 (CDK2). In the case of cisplatin-induced hearing loss, we found that kenpaullone protects hair cells by preventing CDK2 from stimulating the production of toxic reactive oxygen species from the cells' mitochondria.

RG: Which cancer patients are prone to hearing loss? How many of these people are affected?

Zuo: It has been estimated that about 50-70 percent of cancer patients with different types of solid and brain tumors will develop hearing loss.

RG: What is used so far to treat hearing loss in these patients?

Zuo: There is very little. There are no FDA approved compounds. We directly compared our compound to those compounds which are currently in clinical trials and ours performed better in an identical cochlear explant-assay. So we believe our compound will potentially have a better outcome in clinical trials, which is our next goal. We want to submit an Investigational New Drug application and continue with clinical trials.

RG: Would this compound also treat other types of hearing loss?

Zuo: We not only tested its protection against cisplatin-induced hearing loss, but also against noise induced hearing loss, and in fact it was positive in animal models. We found that when you expose mice with 100 decibel (dB) of noise for two hours and then immediately after that you inject this compound the mice will be protected. We believe it is a very effective way to protect against common noise exposure in our society, like at concerts or while lawn mowing. If our compound is effective in those kinds of conditions that would be great.

Furthermore, we believe there are unpublished studies from another lab that also show that kenpaullone is protective against antibiotic treatment-induced hearing loss. Finally, age-induced hearing loss is a massive problem. The theory is that age related hearing loss is an accumulation of noise. Therefore, our drug is potentially protective against age related hearing loss, too. This would be the next phase of our study.

RG: If you could look 20 years into the future, do you think hearing loss will still exist?

Zuo: I definitely think this is a positive step in that direction. Although there have been a lot of failed compounds, we are hopeful. In general, however, drug development is a very lengthy process. So in five to seven years we hope, if it works, patients will benefit. At the moments we are also looking for additional resources to characterize the other top ten compounds we identified. Hearing loss is a very exciting research area, with millions of people around the world affected, so we are hopeful that we can attract funding.

Feature Image: Travis Isaacs via flickr