Medicines like aminoglycoside antibiotics or cisplatin are used to combat life-threatening infections and cancer, respectively, but their use may come at the price of someone’s hearing. Several treatments to prevent the loss of hearing caused by these medicines are currently being developed. Our Translational Research Manager, Dr Carina Santos, tells us more.
Which drugs cause hearing loss?
Several drugs are toxic to our hearing. Aminoglycoside antibiotics are a type of antibiotic that are very effective against several life-threatening infections, like sepsis, tuberculosis, and the respiratory infections that are common in cystic fibrosis patients. Aminoglycosides are also widely used in premature and new-born babies to protect them from infections that their under-developed immune systems cannot cope with, like meningitis. However, although aminoglycoside antibiotics save lives, they are very toxic to the sound-sensing hair cells that line our inner ear and can cause irreversible hearing loss.
Cisplatin is the first line therapy for certain cancers due to its effectiveness in eliminating them; some of these cancers affect children. Similar to the aminoglycosides, cisplatin saves lives, but often at the expense of someone’s hearing. Cisplatin causes permanent and severe high frequency hearing loss in six out of every ten children who are treated with it. Hearing loss may occur within hours or days after the first cycle of cisplatin treatment, or develop after repeated rounds of treatment.
Currently, the only solution for people (many of whom are children) who lose their hearing as a side effect of other treatments are hearing aids and cochlear implants. Neither can prevent the progression of hearing loss or restore lost hearing.
What treatments are under development?
There are around six treatments to prevent hearing loss due to aminoglycosides and cisplatin currently being tested in people and an equal number of treatments being tested in experimental animal models.
Oricula Therapeutics is a US-based company that is developing a drug, ORC-13661, to prevent hearing loss caused by aminoglycoside antibiotics. This drug blocks the entrance of the antibiotic into hair cells, protecting them from damage and consequent hearing loss. This potential future treatment is already being tested in people to see if it is safe to use, in a phase 1 clinical trial. All treatments have to be tested in three phases of clinical trials before they can be approved and made available to everyone. Oricula Therapeutics has recently partnered with another company called Decibel Therapeutics, to accelerate the development of this drug towards patients.
Oricula Therapeutic’s new drug, that could potentially change the life of many people, was discovered through an academic collaboration between Professors Edwin Rubel and Dave Raible from the University of Washington and Dr. Julian Simon from the Fred Hutchinson Cancer Research Center.
They used zebrafish to test thousands of drugs that could potentially protect hair cells from being damaged by aminoglycosides. Zebrafish (see image) are freshwater fish that have hair cells that are similar to the hair cells in our inner ear running along the outside of their bodies. As these cells are on the outside of the body of the fish they are easy to access, which allowed the researchers to test thousands of chemicals and find the one that was most effective in preventing the damage to the hair cells caused by aminoglycoside antibiotics. The researchers later tested this chemical in rats and confirmed its ability to protect hearing.
Their work demonstrates the importance of the research being done at universities all over the world, including research that Action on Hearing Loss supports through its grant schemes. We are currently funding a project at the University of Sussex through our TRIH grant scheme to identify new drugs to protect hearing from aminoglycoside toxicity
Sound Pharma is another US-based company that is currently testing a drug called SPI-1005 for its ability to protect people from aminoglycoside-induced hearing loss in a Phase 2 trial, which is planned to finish in 2019.
Fennec Pharma is the most advanced company in developing a treatment to protect against cisplatin-induced hearing loss. Their drug, called Pedmark, has passed all three stages of clinical trials and should be available to patients within the next two years. The only drawback is that this drug will be used in a very specific group of patients: children being treated with cisplatin to eliminate standard risk hepatoblastoma (a type of liver cancer).
The French company Sensorion are at an earlier stage of developing a treatment to protect against cisplatin-induced hearing loss. They have finished testing the safety of their drug, SENS-401, in a phase 1 clinical trial. The drug did not show any significant adverse effects in people and will soon move into a phase 2 clinical trial to test how effective it is at preventing hearing loss in children undergoing cisplatin treatment. The Spanish company Spiral Therapeutics has also received regulatory approval to test its LPT99 drug in people for the prevention of cisplatin-induced hearing loss.
It is therefore an exciting time in the development of treatments for hearing loss. Although we are still waiting for treatments to pass all the stages of clinical trials and be fully approved for use in patients, five years ago there were less than half the number of treatments in development as there are now. And the more treatments that are tested, the higher the likelihood of finding one that works. This is why we are committed to supporting projects that will lead to the treatments of the future to protect and restore hearing.
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