Can we use gene therapy to prevent hearing loss?

Teachable moment in classrooms:

1. cellular basis of life chapter – concept of one gene, one protein
2. cellular basis of life chapter – concept of gene mutation leading to protein malfunction
3. cellular basis of life – cells can die through programmed cell death
4. special senses chapter – regions of the hearing apparatus
5. special senses chapter – functioning of hair cells in the cochlea

The news item:  Recently the following news item appeared:

Gene Therapy Restores Hearing in Mice – University of Miami Medicine Magazine

esearchers from the Miller School and Harvard Medical School report successfully using gene therapy to help restore hearing in a mouse model mimicking genetic hearing loss in humans. The next step is to study the therapy in humans with a common type of genetic hearing loss.

The article states that very similar to humans, mutations in the gene TMPRSS3 causes late-onset hearing loss in mice. The article also states that this gene affects the survival of inner ear hearing nerve cells, and mutations are responsible for 9% of genetic hearing loss. The article adds that gene therapy in mice was successful in reversing the hearing loss.

So, Why Do I Care??  In the USA over 10,000 babies are born with hearing loss, and 37 million people have hearing loss ranging from mild to severe. Because verbal communication is an important part of information gathering and social activities, hearing loss can lead to a decrease in the quality of life, and social isolation. While hearing aids and cochlear implants have been helpful to restore some degree of hearing, the possibility of gene therapy provides new opportunities to remedy hearing loss.

Plain English, Please!!! First, let’s talk about the location of the hair cells where the gene mutation causes abnormal functioning leading to hearing loss. Our hearing apparatus is made up of three regions: the external ear where the eardrum is, the middle ear where the auditory ossicles are, and the inner ear where the sensory hair cells are located. When we take a closer look we see that the hair cells are found inside a snail-shaped structure called the cochlea. These hair cells are essential for hearing, because they release neurotransmitters to create nerve impulses by the neurons inside the cochlea.

Second, let’s talk about how the TMPRSS3 mutation affects the hair cells. The normal TMPRSS gene encodes for a protein that is a protease. There is no final word on this, but some research suggest that the normal protease helps to maintain normal sodium and potassium levels inside the hair cells, and that protects them from cell death. The mutated TMPRSS3 gene encodes a malfunctioning protease which allows the imbalance of sodium and potassium inside the cells leading to the death of the hair cells. The few surviving hair cells release lower amount of neurotransmitters, the neurons then create fewer nerve impulses, and, thus, hearing loss results.

Third, let’s talk about how gene therapy can reverse hearing loss. It is intuitive that if a cell is suffering from the effect of a malfunctioning protein, then adding the normal version of that protein into the cell can return the cell to normal function. In this particular case the researchers injected a virus into the cochlea, and that virus added a normal TMPRSS3 gene to the hair cells. As a consequence, normal protease was made by the hair cells. This gene therapy is like fixing a flat tire on your car by adding a new tire right next to the flat one. The functional defect is fixed even though the old tire is still there.