Posted by Nicola Robas
Researchers in America have started a clinical trial to test a ground breaking gene therapy which aims to treat hearing loss by restoring sound detecting cells that have been damaged by trauma to the inner ear.

Hearing Loss caused by damage to the inner ear hair cells

When sound enters the ear, it is detected by cells in the inner ear called hair cells. These hair cells (so-called because of the tiny hair-like projections on their surface) are vital to our ability to hear as they convert the pitch and loudness of sound into an electrical signal which is then sent to the brain. Hair cells can be lost during aging and damaged by trauma to the ear such as loud noises and toxic drugs. Following birth, all mammals lose the ability to regenerate hair cells meaning that any damage can lead to a permanent hearing loss. Interestingly birds and amphibians retain the ability to regenerate hair cells throughout their lives. These observations have led to a lot of research into how these regenerative pathways work and how they could be safely activated in people in order to “regrow” lost hair cells and restore hearing.

The “Atoh1 switch”

About 10 years ago a gene called Atoh1 was discovered which acts as a “switch” to turn on hair cell growth. In mammals the Atoh1 switch is turned off following birth but in birds and amphibians it remains on into adulthood. It was discovered that when Atoh1 is artificially switched on in the cells that support hair cells (called “supporting cells”) it instructs them to divide and form new hair cells. This led researchers to investigate whether Atoh1 could be used as a gene therapy to treat certain types of profound hearing loss.

What is gene therapy?

Gene therapy is the introduction of a gene into the human body in order to treat a disease or condition. Gene therapy can be used to replace a faulty gene with a normal copy or activate a gene that has been switched-off. One way of introducing a gene is by incorporating it to a harmless virus which “infects” the appropriate cells and delivers copies of the therapeutic gene. Once inside the cell, the gene is switched on and is able to have its biological effect. A biotech company called Genvec has developed a gene therapy (known by its experimental name CGF166) consisting of virus-delivered Atoh1. In isolated cells, the introduction of CGF166 has been shown to activate Atoh1 biological pathways and in animal models the gene was able to safely restore hearing. Clinical researchers now want to test if CGF166 will have the same beneficial effect in people with profound hearing loss.

A clinical trial to test CGF166 in people

In partnership with Genvec, the pharmaceutical company Novartis has begun a clinical trial to test CGF166 in people for the first time. The goal of this study is to assess whether inner ear infusion of CGF166 is safe and whether it is effective at treating hearing loss. In this first trial, researchers plan to test the therapy in about 45 people who have profound hearing loss in both ears caused by toxic side effects of medicines. This group will have lost a large number of hair cells but will still have intact supporting cells and nerves within the ear. The gene therapy treatment consists of a one-off 20 microlitre (0.02 millilitre) dose injected directly into the inner ear by a surgical procedure that lasts about 45 minutes. Changes in hearing will be monitored before and after treatment. This therapy would not help people with types of inherited deafness where structures in the ear needed to support new hair cell growth are missing or who have damage to the auditory nerve, but researchers believe that CGF166 could potentially benefit people who have acquired their hearing loss through drug toxicity, noise damage and aging.
The clinical trial started in October 2014 and the results are expected in 2017.

More information can be found at the Novartis website