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Dec 21, 2012

Hearing Better Through Chemistry

Drug or stem cell therapies for hearing loss may replace mechanical devices within a few years.

Hearing Better Through Chemistry

Otoprotective drugs are gaining the attention of some large pharma companies. [© robodread - Fotolia.com]

  • For that person in your life with a hearing loss who refuses to countenance a hearing aid, drug or stem cell therapies may replace mechanical devices within a few years. Hearing loss currently affects over 30 to 40 million Americans. Estimates from the NIH and the CDC place the total annual costs of hearing loss at approximately $50 billion per year in the U.S. alone.

  • Causes and Current Treatments

    Throughout life, multiple events including aging can decrease hearing. According to the Mayo clinic, sound exposure over the years can damage inner ear cells. And heredity can render a person more susceptible to ear damage; occupational noises where loud noise is part of the working environment can damage the inner ear, as can recreational noises and some medications and illness. Among medications that can take a toll on hearing are gentamicin and some chemotherapeutic drugs, as well as illnesses that result in high fever.

    Aging remains the leading cause of hearing loss in the U.S., a process characterized by progressive deterioration of auditory sensitivity, loss of the auditory sensory cells, and central processing functions associated with the aging process. It is the third most prevalent chronic condition in older Americans after hypertension and arthritis. Age-related hearing loss (ARHL) is a leading cause of adult hearing handicaps in the United States.

    Unfortunately, humans start out with a relatively small number of auditory hair cells (about 15,000 per cochlea), and these have to last a lifetime. The low number of auditory hair cells present in the cochlea is one of the major reasons hearing loss is so common. According to Sound Pharmaceuticals’ website, once the cells in a particular area of the cochlea are lost, hearing at that frequency is also lost, leaving little in the way of compensatory hearing from neighboring hair cells as they are tuned to respond to a particular frequency. “It is the irreversible injury or loss of auditory hair cells, supporting cells, and neurons that cause the majority of hearing loss,” the site says. Irreversible hair cell death, or apoptosis, is elicited by metabolic or biochemical changes in the hair cells that involve reactive oxygen species or ROS.

    No known cure for age-related hearing currently exists. Available treatment focuses on improving everyday function with devices including hearing aids, telephone amplifiers and other assistive devices, and sign language (for those with severe hearing loss) and speech reading (such as lip reading and using visual cues to aid communication).

    A cochlear implant may be recommended for certain people with very severe hearing loss, with surgery done to place the implant. The implant makes sounds seem louder, but does not restore normal hearing.

    Thomas Meyer, CEO of Auris Medical, a company focused on developing new drugs to treat hearing loss and tinnitus, believes that "the lack of pharmacological treatments is certainly partly due to a lack of detailed understanding of the physiopathology of inner ear disorders, and the fact that the cochlea is a very tiny and complex organ."

    Additionally he commented, lack of a pharmacological benchmark in the form of launched drugs may discourage companies from exploring R&D in this neglected therapeutic area, even with the huge market that exists for effective treatments.

    But while a few companies have dropped out of developing drugs for deafness, among them Buffalo, NY based Kinex, a few companies have stayed in the game, and otoprotective drugs are gaining the attention of some large pharma companies.

  • Potential Treatments Being Tested

    Novartis signed a $214 million deal in 2010 to co-develop gene therapy treatments for hearing loss with Maryland-based GenVec. In 2011, France’s Sanofi a two-year agreement with the Dutch biotech firm Audion Therapeutics to advance small molecule drugs capable of regenerating sensory hair cells in the inner ear.

    Auris Medical and Sound Pharmaceuticals are developing drugs mostly directed at preventing damage and apoptosis that occurs in cochlear cells and neurons of the ear by mitigating oxidative stress.

    Auris’ cell permeable peptide AM-111, a selective JNK MAPK-mediated apoptosis blocker of stress-injured hair cells and neurons in the cochlea is administered by injection into the ear. If applied within a therapeutic window after some traumatic hearing injuries, the company says, the peptide can block JNK MAPK mediated apoptosis of hair cells and cochlear neurons, which would otherwise be permanently lost.

    In its double-blind, randomized, placebo-controlled Phase IIb study with AM-111 conducted in Germany, Poland, and the Czech Republic, Auris enrolled a total of 210 patients suffering from acute acoustic trauma or sudden deafness within the first 48 hours following the incident.

    The trial participants’ hearing loss, measured against a reference value, had to be at least 30 dB at the average of three contiguous audiometric test frequencies. Study participants received one single dose of either AM-111 at 0.4 or 2 mg/mL or placebo by way of i.t. injection and were followed for 90 days. In case of insufficient hearing recovery by Day 7, they were given the option of receiving oral prednisolone as a reserve therapy.

    Preliminary results from the Phase IIb study show that the local treatment with AM-111 was well tolerated. In addition, the study demonstrated a substantial improvement in hearing threshold and speech discrimination score.

    Sound Pharmaceuticals announced on December 5th that the University of Florida has begun enrolling subjects in a study of an oral drug, SF1-1005, testing its ability to prevent hearing loss caused by loud music. Delivered orally as a capsule, Si-1005 contains ebselen, a small molecule that mimics the activity of gluthathione peroxidase (GPx), an enzyme that protects the inner ear from oxidative damage cause by loud sounds or noise. In animal models, ebselen has been shown to help stop oxidative injury and stress in a range of ailments including diabetes, ischemic stroke, acoustic trauma, and hearing loss caused by chemotherapies.

    And last June, Sanofi announced that it had entered into a two-year research contract with pharma company Audion to develop potential treatments for hearing loss through the optimization of small molecules by using a regenerative medicine approach.

    The collaborative research will utilize technology developed at the Massachusetts Eye and Ear Infirmary in the Eaton-Peabody Laboratory, one of the world's largest basic research facilities dedicated to the study of hearing and deafness, by investigator and Audion co-founder Albert Edge, Ph.D., who has strong expertise in stem cells and inner ear biology. Audion licensed Dr. Edge's technology from Mass Eye and Ear.

    Under the terms of the agreement, Sanofi has an option to license technology rights from Audion related to research conducted under the collaboration.

    To date, Amsterdam-based Audion says it has identified several compounds that can regenerate hair cells in laboratory-based cell culture assays, it says.

    For all of us who are aging and facing potential hearing loss, or for individuals who may suffer traumatic hearing loss or from the effects of chemotherapeutic agents, drug developers and stem cell scientists are beginning to look at serious therapeutic options, although they may remain a long way off.


Readers' Comments

Posted 12/21/2012 by Kate

It is indeed an exciting time for hearing loss research. Your readers might also be interested to learn more about the research now underway at Stanford University School of Medicine, as part of the Stanford Initiative to Cure Hearing Loss.

SICHL is comprised of a group of world renowned doctors and researchers with the shared goal of curing hearing loss, and research areas range from inner ear hair cell regeneration to development of non-ototoxic aminoglycoside antibiotics.

The SICHL website is hearinglosscure.stanford.edu

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