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.