It was stated that by inhibiting the receptor, they may be able to eliminate toxic side-effects from the drug that causes hearing loss.
‘Possible way to prevent permanent hearing loss caused by cancer drugs has been discovered. A deeper understanding of how the chemotherapy drug cisplatin works in the body may potentially eliminate the toxic side-effect in childhood cancer survivors and help open the door for potential therapeutics.’
The present study explored the very chemical composition of cisplatin itself for eventually identifying a particular receptor – Toll-like receptor 4 (TLR4, involved in the body’s immune response), that was getting turned on. TLR4 works by crossing the cell membrane, sticking a portion of itself outside the cell to sample the environment, and looking for different signals that indicate damage or danger of some sort.
Permanent Hearing Loss due to Cisplatin
The cells affected by TLR4’s signals are located within the cochlea of the ear, where they play a crucial role in hearing, translating vibrations in the ear into electrical impulses. Cisplatin also accumulates in the kidneys, but the difference is that it can be flushed out and diluted in that area of the body; in a closed system such as the ear, it accumulates and damages the cells.
Hence stopping the signals produced from TLR4 that lead to the accumulation of cisplatin may help prevent the damage. The team thereby examined neuromasts, which are sensory cells within zebrafish that behave similarly to the human hair cells typically damaged by cisplatin.
The study proved that inhibiting TLR4 led to an inhibition of the damage on the sensory cells.
The team also works to refine an inhibitor that can disrupt this sampling process, removing the function that causes the toxic side-effect while still keeping the immune sensor function intact so patients don’t become immunocompromised.
These findings thereby may help open the door for potential therapeutics in cancer and cisplatin-induced ototoxicity.
Source: Medindia
