Preclinical development shows promise to treat hearing loss with Usher syndrome III

July 10, 2012

A new study published in the July 11 issue of the Journal of Neuroscience details the development of the first mouse model engineered to carry the most common mutation in Usher syndrome III causative gene (Clarin-1) in North America. Further, the research team from Case Western Reserve University School of Medicine used this new model to understand why mutation in Clarin-1 leads to hearing loss.

is an incurable genetic disease and it is the most common cause of the dual sensory deficits of and blindness. It affects an estimated 50,000 Americans and many more worldwide. Clinically it is subdivided into types I-III based on the degree of deafness and the presence of and each type is associated with distinct genes. While the progression of the disease is different with each type, all patients ultimately arrive at the same consequence. The focus of this study is Usher type III. More than a dozen are associated with Usher III, with 'N48K' mutation in Clarin-1 being the most prevalent mutation in Usher III patients in North America. Since N48K mutation originated in Europe, results of this study will be of significance to a subset of Usher III patients in Europe as well.

"With the prospective of designing and exploring therapies for Usher III patients with N48K mutation, this is a significant preclinical finding," says Kumar Alagramam, PhD, associate professor of otolaryngology head & neck surgery, genetics, and neurosciences and senior author of the manuscript. "This key understanding of how deafness occurs in Usher III is based on three years of collaborative work."

This new study reports on the first mouse model that mimicked the N48K mutation in Usher III patients. The genetically engineered mouse developed hearing loss similar to clinical presentations observed in Usher III patients with N48K mutation. This model allowed researchers to understand the pathophysiology in fine detail, as there is no non-invasive way to evaluate soft tissue pathology in the human inner ear.

The new study explains why the mutation in the N48K mutation in Clarin-1 leads to – mislocalization of mutant protein in mechanosensory hair cells of the inner ear. Using this new Usher III model, researchers can now explore prospective therapeutics to rescue mutant protein localization and hearing. If successful, this approach could serve as a model to treat Usher I and II associated with missense mutation.

In 2009, Alagramam et al reported on the first mouse model of Usher III. The first mouse model was gene knockout mutation and most recent is a missense mutation, the first model of its kind for Usher III.

Explore further: Study finds new role for protein in hearing

Related Stories

Study finds new role for protein in hearing

August 15, 2011
University of Iowa scientists have discovered a new role for a protein that is mutated in Usher syndrome, one of the most common forms of deaf-blindness in humans. The findings, which were published Aug. 8 in Nature Neuroscience, ...

Treatment approach to human Usher syndrome: Small molecules ignore stop signals

July 1, 2011
Usher syndrome is the most common form of combined congenital deaf-blindness in humans and affects 1 in 6,000 of the population. It is a recessive inherited disease that is both clinically and genetically heterogeneous. In ...

Gene mutation leads to impairment of 2 senses: Touch and hearing

May 1, 2012
People with good hearing also have a keen sense of touch; people with impaired hearing generally have an impaired sense of touch. Extensive data supporting this hypothesis was presented by Dr. Henning Frenzel and Professor ...

Recommended for you

New surgical strategy offers hope for repairing spinal injuries

July 28, 2017
Scientists in the UK and Sweden previously developed a new surgical technique to reconnect sensory neurons to the spinal cord after traumatic spinal injuries. Now, they have gained new insight into how the technique works ...

Scientists block evolution's molecular nerve pruning in rodents

July 27, 2017
Researchers investigating why some people suffer from motor disabilities report they may have dialed back evolution's clock a few ticks by blocking molecular pruning of sophisticated brain-to-limb nerve connections in maturing ...

In witnessing the brain's 'aha!' moment, scientists shed light on biology of consciousness

July 27, 2017
Columbia scientists have identified the brain's 'aha!' moment—that flash in time when you suddenly become aware of information, such as knowing the answer to a difficult question. Today's findings in humans, combined with ...

Social influences can override aggression in male mice, study shows

July 27, 2017
Stanford University School of Medicine investigators have identified a cluster of nerve cells in the male mouse's brain that, when activated, triggers territorial rage in a variety of situations. Activating the same cluster ...

Scientists become research subjects in after-hours brain-scanning project

July 27, 2017
A quest to analyze the unique features of individual human brains evolved into the so-called Midnight Scan Club, a group of scientists who had big ideas but almost no funding and little time to research the trillions of neural ...

Researchers reveal unusual chemistry of protein with role in neurodegenerative disorders

July 27, 2017
A common feature of neurodegenerative diseases is the formation of permanent tangles of insoluble proteins in cells. The beta-amyloid plaques found in people with Alzheimer's disease and the inclusion bodies in motor neurons ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.