WASHINGTON -- By age 65, one out of six adults is afflictedwith severe hearing loss, said Geoffrey Duyk, professor ofgenetics at the Harvard Medical School.

This potentially vast market for biotechnology solutions awaitsthe discovery of the genes that predispose to presbycusis,auditory erosion in adults.

So far, 22 genes for various forms of deafness have beenlocalized, James Snow Jr., director of the National Institute ofDeafness and Other Communication Disorders, told aCongressional budget hearing for the National Institutes ofHealth.

Dominant, progressive hearing loss is among the most commonforms of premature hearing loss, "analogous to Alzheimer'sdisease, a kind of premature senility of the inner ear," WilliamKimberling, director of the center for hereditarycommunication disorders at Boys Town National ResearchHospital at Creighton University, told BioWorld. "I would say 1to 2 percent of adults carry these genes."

Mary-Claire King of the University of California, Berkeley,better known for finding a gene that strongly predisposes tobreast cancer (see BioWorld, April 6), recently mapped a genefor dominant progressive hearing loss to chromosome 5 in anextended Costa Rican family.

And regarding another gene for this disorder, DominicCosgrove, coordinator of the gene experiment laboratory atBoys Town, told BioWorld, "One thing I can say is in the nearfuture there will probably be an announcement involvingdominant progressive."

Otosclerosis, another common hearing disorder, occurs in abouthalf of one percent of adults, according to the AmericanMedical Association's Encyclopedia of Medicine. Bone growsabnormally over the stapes (a bone involved in transmittingsound energy into the inner ear), disabling it.

One responsible gene has been mapped to the X chromosome,and Robert Ruben, professor and chairman of otolaryngology atAlbert Einstein College of Medicine, said he has identified twocandidate genes, but lacks the funds to pinpoint them.

A variety of genes cause syndromes that include deafness. Themost common of these is Usher's syndrome, which afflicts10,000 to 20,000 people in the U.S., said Kimberling. The otherhalf of this syndrome is retinosis pigmentosa.

Kimberling's group has identified five causal genes and mappedfour of them to bands within chromosomes 1, 11 and 14.

Alport's syndrome, still less common, causes progressivehearing loss and nephritis. The responsible gene, located on theX chromosome, expresses collagen 485 in the basementmembrane of both the inner ear and the kidney.

Cosgrove has been developing vectors for gene therapy ofhearing disorders, using the retrotransposon NVL-3. "It is ourhope it will be expressed in the tissues that make the inner andouter hair cells (which convert sound into neuraltransmissions)," he said.

Unlike retroviral vectors, a retrotransposon can insert genesinto non-dividing cells. As such, it could be used not only forhearing disorders but also for neurological disorders such asAlzheimer's and other diseases.

The French biotechnology company Transgene SA (Cedex) andBaxter Healthcare Corp. of Deerfield, Ill., have contactedCosgrove about the vector.

"Steve Rosenberg at NIH is also testing these retrotransposonvectors on his TIL (tumor infiltrating lymphocyte) therapies forcancer," Cosgrove told BioWorld.

Cosgrove also is developing animal models of hearing disorders."Probably one of the greatest areas of commercial interest willbe in subcontracting to use the animals to develop therapies forthe corresponding diseases," he said.

Understanding the genes that cause hearing loss "will give us agreat deal of understanding about the aging process," saidKimberling. It will affect all of us, because we are all going tolose our hearing as we get older.

-- David C. Holzman Washington Editor

(c) 1997 American Health Consultants. All rights reserved.