"Long before it's in the papers"
January 02, 2013

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Drug found to reverse “Alzheimer’s” memory loss in mice

Jan. 2, 2013
Courtesy of FASEB
and World Science staff

A small mol­e­cule, in­jected in­to mice en­gi­neered to have a ver­sion of Alzheimer’s dis­ease, re­verses their mem­o­ry loss, a study re­ports.

The mol­e­cule, called TFP5, fixes ab­nor­mal brain struc­tures called plaques and tan­gles by block­ing an over­ac­tive brain sig­nal, sci­en­tists said.

The find­ings, from sci­en­tists from the Na­t­ional In­sti­tute of Neu­ro­lo­g­i­cal Dis­or­ders and Stroke in Be­thes­da, Md., are pub­lished in Jan­u­ary is­sue of FASEB Jour­nal, a med­i­cal re­search pub­lica­t­ion.

“The next step is to find out if this mol­e­cule can have the same ef­fects in peo­ple, and if not, to find out which mol­e­cule will,” said Ger­ald Weiss­mann, the jour­nal’s editor-in-chief. “Now that we know that we can tar­get the bas­ic mo­lec­u­lar de­fects in Alzheimer’s dis­ease, we can hope for treat­ments far bet­ter – and more spe­cif­ic – than an­y­thing we have to­day.”

Re­search­ers said the drug had no ob­vi­ous tox­ic side ef­fects.

Har­ish C. Pant and col­leagues at the in­sti­tute, part of the Na­t­ional In­sti­tutes of Health, in­jected one group of the sick mice with TFP5, and an­oth­er group with salt wa­ter for com­par­i­son. Af­ter a se­ries of in­jec­tions in­to the ar­ea that con­tains the ab­dom­i­nal or­gans, the treated mice dis­played a “sub­stanti­al re­duc­tion in the var­i­ous dis­ease symp­toms along with restora­t­ion of mem­o­ry loss,” said the Federa­t­ion of Amer­i­can So­ci­eties for Ex­pe­ri­men­tal Bi­ol­o­gy, the pub­lish­er of the jour­nal, in a state­ment Jan. 2. 

The treated ro­dents “ex­pe­ri­enced no weight loss, neu­ro­lo­g­i­cal stress (anx­i­e­ty) or signs of tox­i­city,” the state­ment added. They were al­so found to live an av­er­age of two months long­er than the oth­er group of mice—the equiv­a­lent of five years or so in hu­man terms. The oth­er mice simply got sick­er as their ill­ness pro­gressed nor­mal­ly.

The mol­e­cule was de­rived from an­oth­er mol­e­cule that reg­u­lates the ac­ti­vity of a brain en­zyme called Cdk5, Pant and col­leagues ex­plained. That en­zyme is in turn is im­pli­cat­ed in the forma­t­ion of the plaques and tan­gles that are a hall­mark of Alzheimer’s.

Alzheimer’s, the most com­mon form of de­men­tia, is char­ac­ter­ized by the ac­cu­mula­t­ion of ab­nor­mal struc­tures in brain cells called neu­rons. Sci­en­tists de­scribe these ab­nor­mal­i­ties as as plaques and fi­brous tan­gles, both of which are made up of pro­tein mol­e­cules. Alzheimer’s grad­u­ally rav­ages vic­tims’ mem­o­ries and per­son­al­i­ties by kill­ing these cells. The dis­ease af­fects more than 5 mil­lion Amer­i­cans, in­clud­ing nearly half the popula­t­ion over 85, ac­cord­ing to the Chicago-based Alzheimer’s As­socia­t­ion.

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A small molecule injected into mice engineered to have a version of Alzheimer’s disease reverses their memory loss, a study reports. The molecule, called TFP5, fixes abnormal brain structures called plaques and tangles by blocking an overactive brain signal, scientists said The findings, from scientists from the National Institute of Neurological Disorders and Stroke in Bethesda, Md., are published in January issue of FASEB Journal, a medical research publication. “The next step is to find out if this molecule can have the same effects in people, and if not, to find out which molecule will,” said Gerald Weissmann, the journal’s editor-in-chief. “Now that we know that we can target the basic molecular defects in Alzheimer’s disease, we can hope for treatments far better – and more specific – than anything we have today.” Researchers said the drug had no obvious toxic side effects. Harish C. Pant and colleagues at the institute, part of the National Institutes of Health, injected one group of the sick mice with TFP5, and another group with salt water for comparison. After a series of injections into the area that contains the abdominal organs, the treated mice displayed a “substantial reduction in the various disease symptoms along with restoration of memory loss,” said the Federation of American Societies for Experimental Biology, the publisher of the journal, in a statement Jan. 2. The treated rodents “experienced no weight loss, neurological stress (anxiety) or signs of toxicity,” the statement added. They were also found to live an average of two months longer than the other group of mice—the equivalent of five years or so in human terms—whereas the other mice simply got sicker as their illness progressed normally. The molecule was derived from another molecule that regulates the activity of a brain enzyme called Cdk5, Pant and colleagues explained. That enzyme is in turn is implicated in the formation of the plaques and tangles that are a hallmark of Alzheimer’s. Alzheimer’s, the most common form of dementia, is characterized by the accumulation of abnormal structures in brain cells called neurons. Scientists describe these abnormalities as as plaques and fibrous tangles, both of which are made up of protein molecules. Alzheimer’s gradually ravages victims’ memories and personalities by killing these cells. The disease affects more than 5 million Americans, including nearly half the population over 85, according to the Chicago-based Alzheimer’s Association.