Ex­perts ‘ex­cited’ at break­through in hunt for cure

Daily Express - - FRONT PAGE - By Giles Sheldrick

A COM­MON anti-de­pres­sant could be­come the first drug to halt de­men­tia, ex­perts said last night.

Re­search showed tra­zodone stops brain cells dy­ing, a hall­mark of the in­cur­able con­di­tion.

The drug has al­ready been used to treat peo­ple suf­fer­ing late-stage de­men­tia – but it could be pre­scribed to pa­tients at an early stage of the neu­ro­log­i­cal dis­or­der.

And the brain cell ef­fect was also seen in tri­als of an­other drug called diben­zoyl­methane.

The break­throughs raise the pos­si­bil­ity of an “off-the-shelf” treat­ment for de­men­tia suf­fer­ers in as lit­tle as two years.

Dr Doug Brown, of Alzheimer’s So­ci­ety, said: “We’re ex­cited by the po­ten­tial of these find­ings. As one of the drugs is al­ready avail­able as a treat­ment for de­pres­sion the time taken to get from the lab to the phar­macy could be dra­mat­i­cally re­duced.”

Al­though tra­zodone is cur­rently li­censed as

an anti-de­pres­sant it is be­ing “re­pur­posed” to as­sess its im­pact on other con­di­tions.

Ex­perts hope it will be the first “disease mod­i­fy­ing ther­apy” to tackle the causes of dis­eases like Alzheimer’s rather than mask the symp­toms.

Pro­fes­sor Gio­vanna Mal­lucci, of the Med­i­cal Re­search Coun­cil and the Uni­ver­sity of Cam­bridge, said: “We know that tra­zodone is safe to use in hu­mans so a clin­i­cal trial is now pos­si­ble to test whether the pro­tec­tive ef­fects of the drug we see on brain cells in mice with neu­rode­gen­er­a­tion also ap­plies to peo­ple in the early stages of Alzheimer’s and other de­men­tias.

“We could know in two to three years whether this ap­proach can slow down disease pro­gres­sion, which would be a very ex­cit­ing first step in treat­ing these dis­or­ders.”

Re­searchers found tra­zodone, also known as Moli­paxin when taken to treat ma­jor de­pres­sive dis­or­der, pro­tected against brain dam­age and shrink­age in mice. They are hope­ful the same will hap­pen when it is tested in hu­mans.

It works by block­ing a nat­u­ral de­fence mech­a­nism in cells which is over­ac­tive in the brains of peo­ple with fron­totem­po­ral de­men­tia, Alzheimer’s disease and Parkin­son’s.


The same ef­fect was seen in tri­als us­ing diben­zoyl­methane, a com­pound be­ing tested as a cancer bust­ing drug.

Dr Rob Buckle, chief sci­ence of­fi­cer at the MRC, said: “The two drugs iden­ti­fied re­main ex­per­i­men­tal but they were shown to pro­tect the mice even when given after the pro­cesses un­der­ly­ing neu­rode­gen­er­a­tion had be­come es­tab­lished.

“We cur­rently have no way of treat­ing these dis­eases so the prospect of find­ing drugs that can slow or stop them from pro­gress­ing is ex­tremely ex­cit­ing – even more so when this is based on drugs that have al­ready un­der­gone ex­pen­sive and time con­sum­ing test­ing in un­re­lated stud­ies to es­tab­lish that they are likely to be safe to use in hu­mans.”

Tra­zodone is a sec­ond or third line anti-de­pres­sant with a more se­dat­ing ef­fect than stan­dard medicines like flu­ox­e­tine. Sci­en­tists gave a daily 40mg dose to ro­dents, equiv­a­lent to 194mg in hu­mans. Pa­tients tak­ing the drug for de­pres­sion typ­i­cally re­ceive be­tween 150 to 375mg a day.

The re­search was funded by the MRC, Alzheimer’s So­ci­ety and Alzheimer’s Drug Dis­cov­ery Foun­da­tion.

Neu­rode­gen­er­a­tive dis­eases af­fect more than a mil­lion peo­ple in the UK, in­clud­ing 850,000 with a form of de­men­tia. Re­search shows it dou­bles in preva­lence ev­ery five years above the age of 65, but if on­set could be de­layed by five years, it would be halved.

Dr David Dexter, of Parkin­son’s UK, said: “If these stud­ies were repli­cated in hu­man clin­i­cal tri­als both tra­zodone and diben­zoyl­methane could rep­re­sent a ma­jor step for­ward in the de­vel­op­ment of disease mod­i­fy­ing ther­a­pies for dis­eases like Alzheimer’s.”

The find­ings were pub­lished in the jour­nal Brain.

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