Drug elim­i­nates ra­di­a­tion dam­age in an­i­mals

Mice and mon­keys pro­tected from what could have been lethal doses

The Covington News - - Health & Wellness - By Lauran Neergaard

WASH­ING­TON — Sci­en­tists mim­icked one of can­cer’s sneaky tricks to cre­ate a drug that prom­ises to pre­vent a se­ri­ous side ef­fect of can­cer treat­ment — ra­di­a­tion dam­age — or of­fer an an­ti­dote dur­ing a nu­clear emer­gency.

A sin­gle dose of the ex­per­i­men­tal drug pro­tected both mice and mon­keys from what should have been lethal doses of ra­di­a­tion, re­searchers re­port in Fri­day’s edi­tion of the jour­nal Science.

A study to see if the com­pound is safe in peo­ple could be­gin as early as this sum­mer.

It’s still early-stage re­search, and other ef­forts to cre­ate ra­di­a­tion pro­tec­tants haven’t yet panned out.

But spe­cial­ists are closely watch­ing the work — and the gov­ern­ment is help­ing to fund it — be­cause it’s a new approach to pro­tect­ing the body’s most ra­di­a­tion-sen­si­tive tis­sues from be­ing blasted.

“It has im­por­tant im­pli­ca­tions for ra­di­a­tion ex­po­sure,” said Dr. David Kirsch, a Duke Univer­sity ra­di­a­tion on­col­o­gist who wasn’t in­volved in the drug re­search.

Ra­di­a­tion is a pow­er­ful tool to de­stroy can­cer cells. But cer­tain healthy tis­sues are es­pe­cially sen­si­tive to it, too, par­tic­u­larly the bone mar­row and gas­troin­testi­nal tract.

That vul­ner­a­bil­ity can limit how much ra­di­a­tion physi­cians are able to give can­cer pa­tients.

And when it comes to ra­di­a­tion emer­gen­cies, such as the Ch­er­nobyl ac­ci­dent, full-body ex­po­sure to high doses can cause an ex­tremely lethal “GI syn­drome” that has no treat­ment.

It turns out that ra­di­a­tion doesn’t kill healthy cells in the same way that it kills can­cer cells.

In­stead, bone mar­row and GI cells over­re­act to what should be repara­ble dam­age and com­mit sui­cide, through a well­known process called apop­to­sis, ex­plained An­drei Gud­kov of the Roswell Park Can­cer In­sti­tute, who led de­vel­op­ment of the drug code-named CBLB502.

Learn­ing that was the “eureka” mo­ment, Gud­kov said. Apop­to­sis is the body’s way of stop­ping de­fec­tive cells, with dam­aged genes, from spread­ing.

Tu­mors grow be­cause can­cer cells block apop­to­sis in var­i­ous ways, in­clud­ing by ac­ti­vat­ing a nor­mally dor­mant cell-sig­nal­ing path­way called “nu­clear fac­tor-Kap­paB” or NFKB.

Gud­kov’s team de­cided to try ac­ti­vat­ing that same path­way in healthy tis­sue, to see if it could keep ra­di­a­tion-blasted cells from trig­ger­ing their sui­cide pro­gram.

“We im­i­tated a tu­mor trick,” is how Gud­kov puts it.

The team knew that flag­ellin, a pro­tein from nor­mal gut bac­te­ria, can wake up NFKB. So they cre­ated a drug based on that nat­u­ral pro­tein.

In a se­ries of ex­per­i­ments, they in­jected the drug into mice and rhe­sus mon­keys any­where from 15 min­utes to an hour be­fore ex­pos­ing the an­i­mals to lethal doses of full-body ra­di­a­tion.

The drug dra­mat­i­cally im­proved the an­i­mals’ sur­vival, pro­tect­ing against both bone mar­row and GI de­struc­tion, with no ob­vi­ous side ef­fects.

The drug also im­proved sur­vival when given to mice an hour af­ter fairly high ra­di­a­tion doses, al­though not the very high­est.

A fi­nal ex­per­i­ment showed the drug didn’t block ra­di­a­tion from treat­ing the tu­mors of the mice even as it pro­tected their healthy tis­sue.

Gud­kov founded a com­pany called Cleve­land Bi­o­labs Inc. that is work­ing to bring the drug to mar­ket — both for use in can­cer ra­dio­ther­apy and for biode­fense.

The De­fense De­part­ment and other gov­ern­ment agen­cies are help­ing to fund the re­search.

“For many years, the ra­di­a­tion on­col­ogy com­mu­nity has tried to de­velop ra­dio­pro­tec­tants” based on dif­fer­ent bi­ol­ogy, said Dr. Richard Kolesnick of Me­mo­rial Sloan-Ket­ter­ing Can­cer Cen­ter, who has long re­searched ra­di­a­tion’s ef­fects. “This new in­for­ma­tion on the mech­a­nisms of tis­sue dam­age to the GI tract has re­sulted in a po­ten­tially im­por­tant new drug to pre­vent this lethal GI syn­drome af­ter a ra­di­a­tion ac­ci­dent or po­ten­tial ter­ror­ist at­tack.”

Duke’s Kirsch agreed that the an­i­mal ex­per­i­ments sug­gest the drug has po­ten­tial for ra­di­a­tion emer­gen­cies.

But he stressed that a can­cer role is less clear, be­cause can­cer pa­tients’ big­gest trou­ble comes with late-stage ra­di­a­tion ef­fects, the cu­mu­la­tive buildup of dam­age. “That’s what’s dose-lim­it­ing,” he said.

Pre­scrip­tion shel­ter:


A med­i­cal team cre­ated drug to pro­tect against ra­di­a­tion dam­age from flag­ellin pro­tein.

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