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# NIDCD Director James Battey's 2019 Testimony to the Senate Subcommittee on Labor-HHS-Education Appropriations

## DEPARTMENT OF HEALTH AND HUMAN SERVICESNATIONAL INSTITUTES OF HEALTH

### Fiscal Year 2019 Budget Request

Statement for the RecordSenate Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies

James F. Battey, Jr., M.D., Ph.D.Director, National Institute on Deafness and Other Communication Disorders

**On this page:**
                - Introduction
                - Preventing Hearing Loss Caused by Common Cancer Drugs
                - Treating Hereditary Deafness with Gene Editing
                - Taste, Balance, and More – A Proton Channel with Many Roles
                - Personalized Voices for People with Severely Impaired Speech

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Mr. Chairman and Members of the Subcommittee:

I am pleased to present the President’s Fiscal Year (FY) 2019 budget request for the National Institute on Deafness and Other Communication Disorders (NIDCD) of the National Institutes of Health (NIH).

NIDCD conducts and supports research and research training in the normal and disordered processes of hearing, balance, taste, smell, voice, speech, and language. NIDCD focuses on disorders that affect the quality of life of millions of Americans in their homes, workplaces, and communities. The physical, emotional, and economic impact for individuals living with these disorders is tremendous. NIDCD continues to make investments to improve our understanding of the underlying causes of communication disorders, as well as their treatment and prevention. It is a time of extraordinary promise, and I am excited to be able to share with you some of NIDCD’s ongoing research and planned activities on communication disorders.

## Preventing Hearing Loss Caused by Common Cancer Drugs

NIDCD intramural researchers have discovered why cisplatin and other popular and effective platinum-based chemotherapy drugs cause ototoxicity—damage to the delicate cells in the inner ear which can lead to hearing loss. In previous studies, researchers have focused on why the inner ear is more vulnerable to cisplatin ototoxicity than other areas in the body. The NIDCD research team, however, studied the cause of cisplatin ototoxicity from a different perspective; they explored if cisplatin remains in the inner ear continuing to cause damage for a longer time than in other areas of the body. The scientists found that, both in mice and humans, cisplatin remains in the inner ear long after it is already eliminated from other areas of the body. These results suggest that the inner ear readily takes up cisplatin, but it has little ability to remove the drug.

In mouse and human tissues, the research team saw the highest accumulation of cisplatin was in a part of the inner ear called the stria vascularis, which is responsible for maintaining the positive electrical charge in inner ear fluid that certain cells need to detect sound. The research team determined that the accumulation of cisplatin in the stria vascularis portion of the inner ear contributed to cisplatin-related hearing loss.

This research suggests that if we can find ways to avoid cisplatin from entering the stria vascularis during treatment with cisplatin, we might be able to prevent the hearing loss that goes along with it. As hearing loss is often associated with isolation, depression, and other conditions, helping to preserve hearing in individuals who are required to undergo cancer treatment with these chemotherapy drugs would greatly contribute to maintaining the quality of their lives.

## Treating Hereditary Deafness with Gene Editing

Hearing problems in infants and children can delay the development of voice, speech, and language skills. Approximately 80 percent of hearing loss is due to genetic factors, and treatment options for genetic deafness are limited. A research team, supported in part by NIDCD, used a mouse model of human genetic deafness to design a potential treatment approach. 

Mutations in a particular gene, TMC1, are known to cause hereditary deafness in both humans and mice. The mutation causes the death of sensory hair cells in the cochlea of the inner ear. These hair cells transform sound waves into electrical signals that the brain recognizes as sound. To prevent hair cell death and the resulting progressive hearing loss in mice with the TMC1 mutation, the scientists used the CRISPR-Cas9 gene-editing system to remove the mutation and disable the gene.

The researchers developed a novel approach to deliver the gene-editing complex into the inner ears of newborn mice. They packaged the gene-editing complexes in lipids (fats) that form structures called liposomes. The liposome-packaged complexes move readily through cell membranes into cells. Eight weeks later, substantially more hair cells survived in ears of treated compared to untreated mice. The treatment also significantly reduced progressive hearing loss. This novel strategy may help scientists develop new therapies for hearing loss caused by inherited genetic mutations.

## Taste, Balance, and More – A Proton Channel with Many Roles

Our ability to taste helps us choose and enjoy nutritious foods and avoid foods that have been spoiled by bacteria. On our tongue, sensory taste cells respond to chemicals that are released from food and drink. Taste cells respond to these chemicals via protein receptors and channels that are specific to certain taste molecules. For instance, to detect sourness in food, specialized channels let protons (Hydrogen atoms) that are released from acidic sour-tasting foods enter proton-sensitive, “sour” taste cells on the tongue.

The identity of this “sour detector” protein has been elusive. Now, NIDCD-supported scientists have located a protein called OTOP1 and determined that it forms a channel that allows protons to enter taste cells on the tongue. They have also confirmed that human OTOP1 forms a channel with properties similar to those of the mouse OTOP1 protein. When OTOP1 gene was altered in mice, the scientists observed that taste cells had significantly fewer protons going into them. This evidence, together with other supporting studies on OTOP1, suggests that OTOP1 is the long-sought after sour taste receptor. The next step to test this theory will be to record whether mice that lack OTOP1 respond to sour tastes. Studies like this one, that increase our understanding about how we taste, may help scientists learn to restore a sense of taste to those who have lost it due to disease or injury.

This study may help us understand far more than just how we detect taste. OTOP1 is also required for the vestibular (balance) system in the inner ear to detect gravity, so it is important for helping us keep our balance. OTOP1 is also expressed in many other body tissues, including fat, heart, uterus, breast, and the nervous system. Since we know that OTOP1 functions as a proton-sensitive channel, what we learn from this taste study may help us understand cell signaling in these other tissues, too. When protons enter cells, they change the acid/base (pH) concentration. So, a better understanding of OTOP1 could also help us understand other body processes that involve changes in pH, such as pain sensation, fat metabolism, and pH changes seen in cancer cells. 

## Personalized Voices for People with Severely Impaired Speech

Approximately 2.5 million Americans and millions more people worldwide have a severe speech impairment since birth or as a result of a neurological disorder that occurred later in life, such as a stroke. For these people, communicating is a daily challenge that relies upon their use of a computer to generate their voice. While these devices go a long way toward helping people with a voice disorder express themselves, the synthetic voices produced are usually a poor representation of a natural human voice. In addition, the lack of diversity in available synthetic voices means that many people must use the same generic voice.

Through a Small Business Innovation Research Program grant, NIDCD voice scientists have moved research from the lab into real-world application. Researchers are in the second phase of developing a personalized text-to-speech augmentative and alternative communication (AAC) device called VocaliD. This device involves blending the speech of two individuals—a donor and the recipient. First, a recording is made of whatever vocal sounds the recipient is still able to make. The next step is accomplished with the help of a volunteer voice donor. For the best results, the donor should match the recipient in terms of gender, age, region of origin, and other characteristics. By commercializing VocaliD, NIDCD scientists have refined the technology, automating certain steps and making the entire process of creating personalized, synthetic voices faster and more efficient. These improvements will advance speech synthesis while humanizing machine-mediated spoken interaction for AAC devices and beyond.

## James F. Battey, Jr., M.D., Ph.D.Director, National Institute on Deafness and Other Communication Disorders

James F. Battey, Jr., received his Bachelor of Science degree in physics from the California Institute of Technology in 1974. He received an M.D. and Ph.D. in biophysics from Stanford University School of Medicine in 1980. After receiving training in pediatrics, he pursued a postdoctoral fellowship in genetics at Harvard Medical School under the mentorship of Dr. Philip Leder. Since completing his postdoctoral fellowship in 1983, he has held a variety of positions at the National Institutes of Health, serving in the National Cancer Institute, National Institute of Neurological Disorders and Stroke, and the National Institute on Deafness and Other Communication Disorders (NIDCD). He is married to Frances Battey, and has two sons, Michael and JJ.

August 20, 2018

## CJ

                - FY 2019 Congressional Justification

## Additional Testimony

                - NIDCD Director James Battey's 2019 Testimony to the Senate Subcommittee on Labor-HHS-Education Appropriations