New research suggests that bisphosphonates may help reverse hearing loss in patients who have a specific form of hearing loss. This preliminary report has generated enthusiasm to consider future trials that would utilize more robust methodology in order to determine possible new indications for these “older” bone-strengthening drugs.
Senior author Konstantina Stankovic, associate professor of otolaryngology head and neck surgery and Albert Edge, the Eaton-Peabody Professor of Otolaryngology Head and Neck Surgery, both of Massachusetts Eye and Ear, and colleagues conducted a study that built upon previous findings in mice that showed that a key regulator in bone remodeling, known as osteoprotegerin (OPG), was deficient in mice that developed sensorineural hearing loss (SNHL) and that, in fact, the deficiency actually may have been the cause of the hearing loss. This OPG deficiency sensitized cells to preprogrammed cell death (apoptosis), which also inhibited proliferation and survival of cochlear progenitor cells. These deficient phenotypes, when treated with an exogenous OPG, or the bisphosphonate, zoledronate, were rescued.
The authors write in support of the significance of their work that disabling hearing loss is currently reported to affect 466 million people globally, and that number is expected to nearly double in the next 30 years. Currently, there are no pharmacotherapeutic treatments available. The team’s research was performed on mice that were evaluated prior to intervention to determine hearing capacity and were then exposed to a noise “band” that was known to damage the synapses and contribute to Cochlear neuropathy. The 25 exposed mice were then randomly assigned to either to a subcutaneous injection of saline placebo or 0.5 mg/kg of the bisphosphonate zoledronate 24, 48, and 72 hours after the destructive noise exposure. The hypothesized mechanism for the noise induced disruption of synapses involves excessive release of glutamate into the synaptic cleft, resulting in damage to the postsynaptic neurons. The researchers summarized their results with zoledronate as “striking” and stated that damage caused by the exposure to noise was reversed by the drug’s beneficial effect on the primary afferent synapses, which led to restored peripheral function.
The authors highlight their work as a potential pharmacologic intervention for the most common sensory deficit in the world, noting that the loss of synapses between the cochlear spiral ganglion neurons and hair cells is the cause of SNHL. They also promote the relevance of their findings as setting the stage for additional trials to use medications such as the bisphosphonates that build bone density to potentially treat hearing loss.
According to Dr. Stankovic, “It is our hope that, with further study, we can offer patients who have currently irreversible hearing damage a medication that might stall or reverse their hearing loss.” She added, “This is a significant finding because it opens the possibility for repurposing bisphosphonates, which typically treat severe osteoporosis and metastatic bone disease, for the treatment of sensorineural hearing loss, We hope the promising results from this pilot study can lead to clinical trials within the next several years.”
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