Scientists Prevent Development of Deafness in Animals

Engineered to Have Usher Syndrome

Feb. 4, 2013 Hearing impairment is the most common sensory
disorder, with congenital hearing impairment present in approximately
1 in 1,000 newborns, and yet there is no physiological cure for children
who are born deaf. Most cases of congenital deafness are due to a
mutation in a gene that is required for normal development of the
sensory hair cells in the inner ear that are responsible for detecting
sound. To cure deafness caused by such mutations, the expression of
the gene must be corrected, a feat that has been elusive until recently.
Rosalind Franklin University of Medicine and Science (RFUMS) Assistant Professor
Michelle Hastings and her team, along with investigators at Louisiana State University Health
Sciences Center in New Orleans, Louisiana and Isis Pharmaceuticals in Carlsbad, CA, have
now found a way to target gene expression in the ear and rescue hearing and balance in mice
that have a mutation that causes deafness in humans. The results of the study are reported in
the paper, Rescue of hearing and vestibular function in a mouse model of human deafness,
which was published February 4, 2013 in the journal Nature Medicine.
Dr. Hastings collaborated with research leaders across the country, including RFUMS
colleagues Francine Jodelka and Anthony Hinrich, who were co-first authors on the study, as
well as Dr. Dominik Duelli and Kate McCaffrey; co-first author Dr. Jennifer Lentz at Louisiana
State University Health Sciences Center New Orleans, and Dr. Lentz's research team, including
Drs. Hamilton Farris and Nicolas Bazan and Matthew Spalitta; and Dr. Frank Rigo at Isis
Pharmaceuticals. The collaboration led to the development of a novel therapeutic approach to
treat deafness and balance impairment by injecting mice with a single dose of a small, synthetic
RNA-like molecule, called an antisense oligonucleotide (ASO). The ASO was designed to
specifically recognize and fix a mutation in a gene called USH1C, that causes Usher syndrome
in humans. The ASO blocks the effect of the mutation, allowing the gene product to function
properly, thereby preventing deafness.
Usher syndrome is the leading genetic cause of combined deafness and blindness in humans.
Treatment of these Usher mice with the ASO early in life rescues hearing and cures all balance
problems. "The effectiveness of the ASO is striking," states Hastings. "A single dose of the drug
to newborn mice corrects balance problems and allows these otherwise deaf mice to hear at
levels similar to non-Usher mice for a large portion of their life," she says.
Validating ASO efficacy in the Usher mice is an important step in the process of developing the
strategy for human therapy. Dr. Lentz, who has been studying Usher syndrome for almost 10
years and engineered the mice to model the human disease, states, "Successfully treating a
human genetic disease in this animal model brings the possibility of treating patients much
closer."
The results of the study demonstrate the therapeutic potential of this type of ASO in the
treatment of deafness and provide evidence that congenital deafness can be effectively
overcome by treatment early in development to correct gene expression.
"The discovery of an ASO-type drug that can effectively rescue hearing opens the door to
developing similar approaches to target and cure other causes of hearing loss," says Dr.
Hastings who has been awarded a grant from the National Institute of Health to further develop
the ASOs for the treatment of deafness with Drs. Lentz, Rigo and Duelli.
Story Source:
The above story is reprinted from materials provided by Rosalind Franklin University of Medicine and
Science

Summary:
This article talks about how Michelle Hastings and her team, at the Rosalind Franklin
University of Medicine and Science (RFUMS) identified the gene in mice, that causes them
deafness and balance problems, which also does so in humans. This syndrome is known as
Usher syndrome. Also it explains how they managed to heal those mice with a RNA like
molecule, called antisense oligonucleotide (ASO), which identifies the mutation in a gene which
causes this problem, and fixes it.
This investigation may help to develop a cure for Usher syndrome in humans, which may solve
the major cause of genetic deafness, and sometimes blindness. Though, in order to do this,
experiments must be made on humans first, and probably, a genetic treatment would be very
expensive, so a solution which could help many would only be used by few. Also, in order for the
treatment to be effective, this disease must be recognized in early life, and, parents do not tend
to make genetic analysis to their little children.