Preliminary Animal Study Hints at Cancer Drug’s Ability to Cure NIHL

An article, published in the Science Advances journal, has divulged the results of ‘groundbreaking’ clinical trials, which have shown that an already approved drug may be able to protect and treat sensorineural hearing loss in humans.[i]

At present, there are no medicines approved by the US Food and Drug Administration (FDA) for the management of hearing impairment. The same can be said for the UK Medicines and Healthcare products Regulatory Agency (MHRA).

However, new tests, undertaken by researchers at the Creighton University School of Medicine, have found that growth blocker, dabrafenib, could provide a solution.

In both the US[ii] and the UK,[iii] dabrafenib is authorised to treat a range of cancers [unresectable and metastatic melanoma, stage 3 melanoma (where tumours have been surgically removed), advanced non-small cell lung cancer, thyroid and biliary tract cancers, etc.], typically in combination with another growth blocker, called trametinib.

At Creighton, mice were treated with dabrafenib, before being continuously exposed to 100 dB noise in the 8-to-16 kHz octave band for 2-hours (a noise dose capable of causing permanent hearing loss).

Results indicated that dabrafenib provided ‘significant hearing protection’ under these conditions.

In an alternative scenario, Creighton researchers treated the mice with dabrafenib (and in combination with compound AZD5438) starting 24-hours after being exposed to noise.

Hearing protection was demonstrated in test subjects given dabrafenib-only, while ‘full protection’ was achieved in subjects that received combination therapy.

The fact that both pre- and post-exposure treatments were effective in animal models meant that hearing was protected not just proactively (when injurious noise exposure is predicted), but also reactively (when injurious noise exposure is unpredictable).

Dabrafenib treats cancer by inhibiting activation of a specific cellular pathway (targeting BRAF/MEK/ERK genes) that is known to enhance cell growth by proliferating tumour cells. In light of the positive results to emerge from this study, it is theorised that the drug can also prevent non-dividing hair cells in the ear from cellular death via this same metabolic pathway.

Study Author and Assistant Professor at the institution’s Department of Pharmacology and Neuroscience, Tal Teitz, PhD, described findings as ‘very exciting’ and remarked that dabrafenib poses as a ‘good [medication] candidate’, because its side effects are ‘known and relatively minimal’ (headaches and skin rash are manageable). N.B. The MHRA has previously cautioned administering the drug cocktail to those at risk of gastrointestinal perforation and colitis.[iv]

Meanwhile, Matthew Ingersoll, PhD, the Lead Author and day-to-day handler of experimental laboratory work, deemed findings to represent an ‘incredibly promising’ development in the field of hearing, even though these were only preliminary animal studies and may have no bearing on medicinal effectiveness in humans.

As such, there have been calls for more studies to explore if and how BRAF kinase inhibitors, like dabrafenib, can work to circumvent hair cell death in the human inner ear.

Should future studies compliment the Science Advances paper, academics are optimistic that dabrafenib can be repurposed as a noise-induced hearing loss (NIHL) prevention method – a prospective topic of conversation in occupational disease litigation?

Repurposing drugs with prior authorisation is an attractive prospect, because it can drastically reduce both the development timeline (by between 5-to-8-years) and costs (by up to 40%). Compared to the ‘highly invasive and expensive’ surgical options currently available, e.g. cochlear implants, orally-taken dabrafenib therefore offers the ‘least invasive and most cost-effective mode of treatment’.

 

[i] Ingersoll MA et al., BRAF inhibition protects against hearing loss in mice. Science Advances. 2 Dec 2020: Vol. 6, no. 49, eabd0561 <https://advances.sciencemag.org/content/6/49/eabd0561/tab-pdf> accessed 26 January 2021.

[ii] ‘HIGHLIGHTS OF PRESCRIBING INFORMATION’ (April 2018 US FDA) <https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/202806s008lbl.pdf> accessed 29 January 2021.

[iii] ‘Dabrafenib (Tafinlar) and Trametinib (Mekinist)’ (Cancer Research UK) <https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/dabrafenib-trametinib> accessed 29 January 2021.

[iv] Medicines and Healthcare products Regulatory Agency, ‘Trametinib (Mekinist▼): risk of gastrointestinal perforation and colitis’ (12 March 2016 GOV.UK) <https://www.gov.uk/drug-safety-update/trametinib-mekinist-risk-of-gastrointestinal-perforation-and-colitis> accessed 29 January 2021.