Researchers have shown that mifepristone, a drug currently FDA-approved for chemical abortion, prevent the growth of vestibular schwannoma (also known as acoustic neuroma) cells. This sometimes-lethal intracranial tumor typically causes hearing loss and tinnitus. The study was published in Scientific Reports.

"Currently, there are no FDA-approved drugs for vestibular schwannomas or the associated hearing loss," said Konstantina Stankovic, M.D., Ph.D., an ear, and skull base surgeon and auditory neuroscientist at Mass. Eye and Ear and Harvard Medical School who led the study.

"Therefore, there is an unmet medical need to discover drugs with minimal adverse effects that would treat this tumor and reduce or obviate the need for surgery and radiation." Although histologically non-malignant, vestibular schwannomas are dangerous due to their location.

Arising from the Schwann cells of the vestibular (balance) nerve, these tumors can grow to the point of damaging nearby structures and can lead to death by compressing the brainstem. By compressing nerves in the internal auditory canal, the tumors can cause dizziness and facial nerve paralysis, in addition to hearing loss.

Though vestibular schwannomas affecting both sides are the hallmark of neurofibromatosis type 2 (NF2), a genetic disorder causing tumors to grow at multiple sites throughout a person's life, vestibular schwannomas may also occur sporadically, and on one side only.

Then, through a survey of more than 1,100 drug candidates (all FDA-approved), they identified a short list of drugs likely to convert the abnormal transcriptional signature of a tumor to a more normal one. They then tested eight of the most promising candidate drugs against cells grown from other human vestibular schwannomas.

Their experiments showed that one drug, mifepristone, was most effective. Treatment of vestibular schwannoma cells with mifepristone reduced their proliferation rate by 80%. "Our investigation represents the first application of algorithm-based repositioning of FDA-approved drugs for this tumor class," said first author Jessica Sagers.

Mifepristone is an attractive candidate for repurposing, as it is relatively safe, well studied and carries minimal adverse effects. FDA-approved in 2000, mifepristone is most often used together with another medication, misoprostol, to end an early pregnancy. Adverse effects of mifepristone include mild fatigue, hot flashes, nausea, and rash. Long-term use of mifepristone has been studied in clinical trials for other tumors, with minimal adverse effects reported after years of usage.

The authors are cautiously optimistic about the therapeutic potential of mifepristone for patients with vestibular schwannomas, either from NF2. They hope to begin a phase II clinical trial at Mass. Eye and Ear soon to determine the efficacy of the drug for this indication. They are optimistic about the potential to repurpose this relatively safe drug for patients desperately in need of better solutions.