Clin­i­cal ben­e­fit of mul­ti­ple scle­ro­sis drug dis­cov­ered Aat

Pakistan Observer - - KARACHI CITY -

DRUG whose clin­i­cal ben­e­fit in treat ing mul­ti­ple scle­ro­sis was dis­cov­ered

Rush Univer­sity Med­i­cal Cen­tre was ap­proved by the Food and Drug Ad­min­is­tra­tion on Jan­uary 22 and is now avail­able in the U.S.

The drug, called dal­fam­pri­dine, is the first ther­apy for mul­ti­ple scle­ro­sis that can be taken orally. It is also the first FDA-ap­proved ther­apy to treat im­paired walk­ing, a de­bil­i­tat­ing symp­tom of the dis­ease-lim­it­ing pa­tients’ in­de­pen­dence and abil­ity to ac­com­plish the most ba­sic tasks of daily liv­ing. While other mul­ti­ple scle­ro­sis drugs work by de­creas­ing the in­flam­ma­tion that causes dam­age to the cen­tral ner­vous sys­tem, dal­fam­pri­dine is de­signed to al­low con­duc­tion of nerve im­pulses de­spite the dam­age.

Re­search that led to the dis­cov­ery of dal­fam­pri­dine’s ther­a­peu­tic value dates back to the 1960s, when Dr. Floyd Davis, then a neu­rol­o­gist in train­ing and later a physi­cian at Rush, be­came in­trigued by an un­usual clin­i­cal ob­ser­va­tion: many mul­ti­ple scle­ro­sis pa­tients fare bet­ter when their body temperature is slightly low­ered, even by just two- or three-tenths of a de­gree.

“In mul­ti­ple scle­ro­sis, the pro­tec­tive myelin sheath that wraps around nerve fibers in the brain and spinal cord is dam­aged, es­sen­tially caus­ing a short cir­cuit,” said Davis, who is now re­tired. “Some­how, lower body temperature en­abled the elec­tri­cal pulse to con­tinue its travel along the nerve fibers. I was com­pletely trans­fixed by the sig­nif­i­cance of that fact.”

It was im­por­tant be­cause it showed “that the dam­aged nerve fibers were not doomed, as pre­vi­ously be­lieved,” said Dr. Du­san Ste­foski, di­rec­tor of the Rush Mul­ti­ple Scle­ro­sis Cen­ter, who teamed up with Davis in 1978, shortly af­ter com­plet­ing neu­rol­ogy train­ing at Rush. Davis launched a se­ries of lab­o­ra­tory stud­ies to un­der­stand the mech­a­nism that ex­plained the no­tice­able im­prove­ment in symp­toms.

He then looked for a com­pound that could mimic some of the ef­fects of lower body temperature and learned of 4aminopy­ri­dine, or dal­fam­pri­dine, which blocks the potas­sium ion chan­nels in nerve fibers. “The chem­i­cal was com­monly used in phys­i­ol­ogy lab­o­ra­to­ries where sci­en­tists were study­ing nor­mal nerve con­duc­tion, but at the time it was used clin­i­cally only by physi­cians in Bul­garia, then a Com­mu­nist-block coun­try,” Davis said. “They didn’t know how it worked, but they used it to help pa­tients re­cover from anes­the­sia-in­duced paral­y­sis more quickly.”

In 1983, in a small proof-of-con­cept study, Davis and Ste­foski in­jected the drug in 11 pa­tients whose mo­tor func­tion and eye­sight were im­paired be­cause of mul­ti­ple scle­ro­sis. “It was stun­ning,” Ste­foski said. “Af­ter a sin­gle in­tra­venous dose, the pa­tients could walk bet­ter and see bet­ter.” Rush was granted mar­ket ex­clu­siv­ity by the FDA un­der the Or­phan Drug Act of 1983 and li­censed world­wide rights for dal­fam­pri­dine first to Ire­land-based Elan Cor­po­ra­tion and sub­se­quently to Acorda Ther­a­peu­tics, Inc., lo­cated in Hawthorne, New York.

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