Posts tagged congenital deafness

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.

(Source: eurekalert.org)

ScienceDaily (July 25, 2012) — A new gene therapy approach can reverse hearing loss caused by a genetic defect in a mouse model of congenital deafness, according to a preclinical study published by Cell Press in the July 26 issue of the journal Neuron. The findings present a promising therapeutic avenue for potentially treating individuals who are born deaf.

(Credit: © Vasiliy Koval / Fotolia)

"This is the first time that an inherited, genetic hearing loss has been successfully treated in laboratory mice, and as such represents an important milestone for treating genetic deafness in humans," says senior study author Lawrence Lustig of the University of California, San Francisco.

Hearing loss is one of the most common human sensory deficits, and it results from damage to hair cells in the inner ear. About half of the cases of congenital hearing loss are caused by genetic defects. However, the current treatment options — hearing amplification devices and cochlear implants — do not restore hearing to normal levels. Correcting the underlying genetic defects has the potential to fully restore hearing, but previous attempts to reverse hearing loss caused by genetic mutations have not been successful.

Addressing this challenge in the new study, Lustig and his team used mice with hereditary deafness caused by a mutation in a gene coding for a protein called vesicular glutamate transporter-3 (VGLUT3). This protein is crucial for inner hair cells to send signals that enable hearing. Two weeks after the researchers delivered the VGLUT3 gene into the inner ear through an injection, hearing was restored in all of the mice. This improvement lasted between seven weeks and one and a half years when adult mice were treated, and at least nine months when newborn mice received the treatment.

The therapy did not damage the inner ear, and it even corrected some structural defects in the inner hair cells. Because the specific gene delivery method used is safe and effective in animals, the findings hold promise for future human studies. “For years, scientists have been hinting at the possibility of gene therapy as a potential cure for deafness,” Lustig says. “In this study, we now provide a very real and big step towards that goal.”

Source: Science Daily