Aug 2017 University of Maryland

Researchers at the University of Maryland  have announced a breakthrough discovery that could eventually help scientists repair hearing problems or protect those at risk for hearing loss – a condition that affects some 40 million Americans. In particular, with 74,000 children currently affected by profound, early-onset deafness, scientists have been trying to solve the mystery of what causes hearing disorders, especially those that may have genetic causes. The study has identified a crucial protein in the process that turns sound waves into brain signals. The new understanding could eventually help repair or prevent hearing problems for those with the highest risk. The findings were published recently in the Nature Communications. The study is the first to illuminate in detail how the protein, known as CIB2, enables hearing. CIB2, which is short for calcium and integrin-binding protein 2, is essential for the structure of stereocilia, the structures at the top of the sensory hair cells in the inner ear. Stereocilia are extremely small, less than a half a micrometer in diameter, which is about the wavelength of a visible light. Each ear contains 18,000 hair cells that do not divide or regenerate.

The researches discovered five years ago that CIB2 was involved in hearing. Since then, they have studied the protein in flies, mice, zebrafish and humans. The new study is the first to explain the mechanism behind CIB2 in hearing. In this study, they genetically engineered mice without CIB2, as well as mice in which a human CIB2gene mutation had been inserted. The researchers found that the human mutation affects the ability of the CIB2 protein to interact with two other proteins, TMC1 and TMC2, which are crucial for converting sound to electrical signals, a process known as mechanotransduction. People with this mutation cannot turn soundwaves into signals the brain can interpret, and so are deaf. When the researchers inserted the human CIB2 mutation into the mouse, they found that the mice were deaf.

The researchers are now looking for other molecules beyond CIB2 that play a key role in hearing. In addition, they are exploring potential therapies for CIB2-related hearing problems. In mice, they are using the gene editing tool CRISPR to modify dysfunctional CIB2 genes. They suspect that if this modification occurs in the first few weeks after birth, these mice, which are born deaf, will be able to hear. The scientists are also experimenting with gene therapy, using a harmless virus to deliver a copy of the normal CIB2 gene to baby mice that have the mutated version. Early results of these experiments are intriguing.