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Mifepristone – Abortion Drug for Tumor That Causes Hearing Loss

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Highlights:
  • Mifepristone may halt the growth of human vestibular schwannoma.
  • Human vestibular schwannoma is a benign tumor that causes hearing loss.
  • Mifepristone is an FDA-approved drug for chemical abortion.

Mifepristone – Abortion Drug for Tumor That Causes Hearing Loss

Abortion drug for treatment of hearing loss
Mifepristone may halt growth of intracranial tumor that causes hearing loss.

Mifepristone, an FDA-approved drug for chemical abortion may prevent the growth of vestibular schwannoma (also known as acoustic neuroma) cells, according to recent research at the Massachusetts Eye and Ear Infirmar.

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The findings suggest that mifepristone is a promising drug candidate to be repositioned for the treatment of these tumors. This intracranial tumor typically causes hearing loss and tinnitus.

"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."
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Tumor that leads to hearing loss
Vestibular schwannomas, though histologically non-malignant, are dangerous due to their location. Originating 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. The tumors can cause dizziness and facial nerve paralysis, in addition to hearing loss by compressing nerves in the internal auditory canal.

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.

According to current treatments options, patients with symptomatic or growing vestibular schwannomas can undergo surgical resection (through craniotomy) or radiation therapy; however, both of these procedures come with significant risks.

The research team first performed the largest meta-analysis of the vestibular schwannoma transcriptome by studying 80 tumors from patients with sporadic and NF2-associated vestibular schwannomas. 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 in particular, mifepristone, was most effective. Treatment of vestibular schwannoma cells with mifepristone reduced their proliferation rate by 80 percent.

"Our investigation represents the first application of algorithm-based repositioning of FDA-approved drugs for this tumor class," said first author Jessica Sagers, a PhD student at Harvard Medical School.

Mifepristone
Mifepristone is a candidate drug 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.

The side 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 study authors are cautiously optimistic about the therapeutic potential of mifepristone for patients with vestibular schwannomas, either from NF2 or those arising sporadically. Dr. Stankovic hopes to begin a phase II clinical trial at Mass. Eye and Ear soon to determine the efficacy of the drug for this indication.

"We are optimistic about the potential to repurpose this relatively safe drug for patients desperately in need of better solutions," she said.

References :
  1. Jessica E. Sagers, Adam S. Brown et al. Computational Repositioning and Preclinical Validation of Mifepristone for Human Vestibular Schwannoma, Scientific Reports doi:10.1038/s41598-018-23609-7


Source: Medindia

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