DRUGS TO MAKE THE NOISES STOP

Guru Magazine - - IN THE NEWS -

Imag­ine a noise in your ear that never goes away – like a party in your head that you’re not in­vited to. For peo­ple who suf­fer tin­ni­tus, this can be a daily re­al­ity. A so­lu­tion could be on the hori­zon: sci­en­tists have man­aged to pre­vent tin­ni­tus de­vel­op­ing in mice ex­posed to ex­ces­sive lev­els of noise us­ing a drug that’s usu­ally used to treat epilepsy. Tin­ni­tus af­fects about one in ten adults; for some it can be a truly de­bil­i­tat­ing con­di­tion for which there are few ef­fec­tive treat­ments, and no known cure. In fact, there are on-go­ing dis­agree­ments be­tween some ex­perts about what tin­ni­tus even is. The symp­toms vary enor­mously, from a whis­per to a roar, con­stant to in­ter­mit­tent, tem­po­rary to per­ma­nent, in one ear, or both. Tin­ni­tus can be trig­gered by re­peated ex­po­sure to ex­ces­sively loud noise, cer­tain pre­scrip­tion drugs, mid­dle ear in­fec­tions and old age, among other things. The most com­mon trig­ger is loud noise, which seems to bring about more per­ma­nent symp­toms than when it is in­duced by medicines. Re­searchers have re­cently be­gun mak­ing sense of some of the bi­ol­ogy be­hind tin­ni­tus. An im­por­tant process be­hind noise-in­duced tin­ni­tus is thought to be

over-ac­tiv­ity of cells in a spe­cific part of the brain (called the dor­sal cochlea

nu­cleus (DCN)). Like a rock con­cert mix­ing desk, this is the first re­lay sta­tion in the pro­cess­ing path­way from the ears to the brain: it is at the DCN where the au­di­tory nerve, car­ry­ing signals from the in­ner ear, first con­nects with brain cells. Th­ese cells are nor­mally ac­ti­vated in re­sponse to real sounds, so the ex­pe­ri­ence of the phan­tom sounds in tin­ni­tus could be due to over-ac­tiv­ity in this re­gion.

A faulty mix­ing desk Ex­plor­ing the DCN fur­ther, re­searchers at the Univer­sity of Pitts­burgh School of Medicine looked at molec­u­lar­sized chan­nels cov­er­ing the sur­face of the nerve cells there. Th­ese spe­cial ‘pores’ (called KCNQ ion chan­nels) trans­port potas­sium into and out of brain cells. KCNQ chan­nels nor­mally

have a calm­ing ef­fect on the DCN – in­hibit­ing the ac­tiv­ity of the cells there. So the sci­en­tists rea­son that tin­ni­tus could be due to th­ese chan­nels not work­ing nor­mally. And sure enough, the epilepsy drug reti­ga­bine, which is al­ready known to in­crease KCNQ chan­nel ac­tiv­ity, pre­vented tin­ni­tus de­vel­op­ing in mice ex­posed to ex­ces­sively loud noise. Un­treated mice ex­posed to the noise be­haved as though they had tin­ni­tus. Al­though this study seems to have iden­ti­fied a new process in­volved in noise-in­duced tin­ni­tus, it is not the first time a drug has been used to treat the con­di­tion. One prob­a­ble fac­tor in­volved in tin­ni­tus is over­pro

duc­tion of glu­ta­mate, a chem­i­cal messenger pro­duced by the spe­cial ‘ hair’ cells in the in­ner ear. Glu­ta­mate trans­mits the hairs’ move­ment

from the in­ner ear to au­di­tory nerves, where it is con­verted into elec­tri­cal im­pulses that travel to the DCN, and ul­ti­mately the brain. Loud noise can cause too much glu­ta­mate to be made, and it is this ex­cess that de­stroys the vi­tal con­nec­tions be­tween the in­ner ear and the au­di­tory nerve – an ef­fect known as ‘ex­ci­to­tox­i­c­ity’. The con­nec­tions that re­grow to re­place those de­stroyed be­come over­ac­tive, and this is thought to cause tin­ni­tus. Fi­nally! Some­thing that sounds like a cure A pa­per pub­lished in 2007 found that ifen­prodil, a drug which blocks cer­tain glu­ta­mate re­cep­tors, not only pre­vented noise-in­duced tin­ni­tus when put di­rectly into the in­ner ear, but could re­verse the

ef­fects, pro­vid­ing it was ad­min­is­tered within four days. How th­ese two mech­a­nisms are re­lated (they could be dif­fer­ent stages of the same tin­ni­tus for in­stance, or be due to dif­fer­ent types) is not clear, but the team be­hind the re­cent study now plan to de­velop a drug specif­i­cally de­signed for tin­ni­tus. They say such a pre­ven­ta­tive drug could be use­ful for soldiers or peo­ple who have to work in very noisy con­di­tions. Ex­cit­ingly, the work may even have im­pli­ca­tions for other phan­tom sen­sa­tions such as the phan­tom limbs ex­pe­ri­enced by am­putees.

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