It’s 1970, and everyone knows that there is no treatment for nerve deafness. But by 1984, the US Food and Drug Administration approved the first cochlear implant, leading to advanced computerized devices that let deaf people hear and understand speech. Thirty years later there are clinical trials to see whether gene therapy can restore hearing without implants or can improve implant function. And stem cell implantation may be just a few years behind.
Gene Therapy
Genes are the basic units of inheritance, passed from parent to child. They are located on chromosomes and contain codes for producing specific proteins. These specific proteins determine the structure and function of the body, basically making us what we are.
Gene therapy uses genes that are modified by scientists to prevent or treat many types of disorders, including hearing loss. If a gene has stopped working properly, in theory it can be replaced with a working gene. Alternatively a new gene can be manufactured that will create improvement of function. Ongoing trials examine restoration of hearing by insertion of new genes into the inner ear. The goal is to create new hair cells or to improve function of existing hair cells.
Gene therapy for deafness is investigational at the time of writing, but research has advanced to the point of human research trials. Although promising for the treatment of genetic disorders, some types of cancer, blindness, and deafness, it has not yet been proven safe and effective.
To move new genes into cells, a transporting vector is used, most commonly a safe virus that cannot reproduce itself. Scientists attach genes to viral vectors that are known to be safe and have the ability to penetrate into cells. The vector enters a cell and deposits the new gene. The new gene causes the cell to make functioning proteins to replace the faulty proteins that cause disease. Clinical trials have shown promise in the treatment of leukemia, hemophilia, and retinitis pigmentosa.
Animal studies show that gene therapy can regenerate auditory nerve cells. While the goal of therapy is to regenerate hair cells and promote natural hearing, a preliminary goal of auditory nerve cell (not hair cell) regeneration may be easier to accomplish and improve function with cochlear implants.
The first human trial of gene therapy for deafness is now underway. It treats deaf patients with a gene called ATOH1 attached to a harmless viral vector.
Research on the gene Islet1 (ISL1) is directed at preventing age-related hearing loss. Normally ISL1 is involved in development of hair cells but permanently turns itself off after the hair cells are formed in the embryo. When modified ISL1 was vectored into mouse hair cells, it reprogrammed the hair cells to continuously produce ISL1. This reduced age-related hearing loss in the mice.
Stem Cell Therapy
Embryonic stem cells have the capacity of generating all cell types in the body. Unfortunately, when embryonic stem cells are transplanted from a fetus into a patient, they are rejected like any other transplant. To prevent rejection, powerful drugs that partially disable the immune system are required to keep the stem cells alive. Of course disabling the immune system is not a good idea.
Fortunately, the temporary ban on embryonic research led scientists to discover a way to reprogram a patient’s own cells into stem cells. Called induced pluripotent stem cells (iPS cells), they are transformed from skin or other cells of the patient and function like embryonic stem cells. But since they are taken from the patient herself, iPS cells do not require disabling the immune system. Like new genes used in gene therapy, iPS cells can be delivered to the inner ear by attaching them to inactivated viral vectors.
The inner ear is a prime organ for stem cell therapy because even in deaf patients it remains mostly intact, except for the hair cells. Current research is focusing on producing human hair cells in the laboratory. From there they could be transplanted into the cochlea or be used to identify new drugs to combat deafness. Scientists have already used stem cells to form auditory nerve fibers that can connect to existing hair cells in experimental animals.