Study has potential to uncover new therapeutic approaches
Cleveland - April 13, 2009 - Qing Yin Zheng, M.D., assistant professor of Otolaryngology-Head and Neck Surgery and Genetics at the Case Western Reserve University School of Medicine, and member of the Case Comprehensive Cancer Center, has been awarded a five year $1.66 million grant from the National Institutes of Health (NIH) Research Project Grant Program (R01) to explore the impact of several molecular pathways on inner ear dysfunction in Ushers syndrome.
Usher Syndrome (USH) is a clinically and genetically heterogeneous disorder characterized by congenital deafness and retinitis pigmentosa. It is the most common cause of deafness accompanied by blindness. *There are about 10-15,000 people with Usher syndrome in the United States today and it accounts for 6 percent of the congenitally deaf population and more than 50 percent of the deaf- blind population. While there is currently no medical treatment for Usher syndrome, cochlear implants have been found to be very affective in patients with severe or profound hearing loss.
"Many USH patients benefit from cochlear implants, but preservation and a minimal density of spiral ganglion cells are required for an effective implant," said Zheng.
Spiral ganglion cells are the cells that provide the sense of hearing by sending sound waves from the cochlea to the brain. Dr. Zheng believes residual hair cells in the cochlea could promote the survival of the spiral ganglion neurons by release of neurotrophic substances or growth factors, and as a result he is particularly interested in the discovery of therapeutic targets that prevent hair cell death, as this is the key to helping Usher 1 patients to respond to cochlear implants and other treatment options successfully.
"Hair cell replacement or regeneration therapies have not really solved the deafness problem of ear diseases," said Zheng. "An alternative to replacing lost hair cells is to prevent their loss in the first place."
This grant is Dr. Zheng's fourth NIH grant for research involving auditory disease with accumulated $4 million funding.
"A clear translational goal, expertise of his research team and a very strong publication record, Dr. Zheng has potential to uncover new therapeutic approaches to treat hearing loss in Usher syndrome. I'm very grateful for the NIH for its forward-thinking commitment to Dr. Zheng and his innovative medical science research," said Dr. James Arnold, Julius McCall Professor and Chair of the Department of Otolaryngology - Head and Neck Surgery at Case Western Reserve University School of Medicine.
Dr. Zheng aims to: 1) identify the mutation in and characterize a new mouse deafness model (for Usher 1 syndrome and presbycusis or age-related hearing loss) that provides an ideal window of time for evaluating drug therapy; 2) identify key molecules and mechanisms that lead to hair cell death and hearing loss in the models for the Usher 1 syndrome; 3) prove the concept that genetic hearing loss and hair cell death can be prevented by otoprotection therapy.
"We are very honored and pleased that our department has been given this significant award from the NIH," says Dr. Cliff Megerian, Richard W. and Patricia Pogue Professor of Auditory Surgery and Hearing Sciences at University Hospitals Case Medical Center. "The impact of deafness on quality of life and language development is devastating. The financial impact and individual human suffering are devastating, due to the lack of effective drug therapy," adds Dr. Megerian who has collaborated on several research projects with Dr. Zheng.
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and 15th largest among the nation's medical schools for research funding from the National Institutes of Health. Eleven Nobel Laureates have been affiliated with the school.
The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching and in 2002, became the third medical school in history to receive a pre-eminent review from the national body responsible for accrediting the nation's academic medical institutions. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themessearch and scholarship, clinical mastery, leadership, and civic professionalism prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century.
Annually, the School of Medicine trains more than 600 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News and World Report Guide to Graduate Education. The School of Medicine's primary clinical affiliate is University Hospitals and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic Foundation, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. casemed.case.edu.
*About Usher Syndrome (from www.hearseehope.com/usherSyndrome.htm)
There are three different clinical types of Usher syndrome. They are called Usher syndrome type 1 (US1), Usher syndrome type 2 (US2), and Usher syndrome type 3 (US3). All types of the syndrome are inherited in the same pattern s autosomal recessive traits.
Usher syndrome type 1 (US1) - People with US1 are born nearly deaf. Eyesight usually begins degrading around the age of 5-10, beginning with night blindness. Generally night blindness precedes tunnel vision by years or even decades. The duration of becoming legally blind spans from as early as childhood to as late as the 40's. People with US1 also struggle with balance or homeostasis, which is the biological balance within the human body. Because of the balance problems, children with US1 are slow to sit without support and rarely learn to walk before they are 18 months old.
Usher syndrome type 2 (US2) - People with US2 are born with moderate to severe hearing impairment and normal balance. Although the severity of hearing impairment varies, most of these children perform well in regular classrooms and can benefit from hearing aids. Retinitis Pigmentosa, which is a degeneration of the retina (the part of the eye that receives images of objects), is characterized by blind spots that begin to appear shortly after the teenage years. The visual problems in US2 tend to progress more slowly than the visual problems in US1.
Usher syndrome type 3 (US3) - With US3, hearing loss and vision loss due to RP are both progressive.