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“Unprecedented” results after new Alzheimer’s treatment

Jan. 9, 2008
World Science staff

In find­ings de­scribed as “dra­matic and un­prece­dent­ed,” re­search­ers say they have found an in­jec­tion treat­ment that leads to marked, sus­tained im­prove­ments in Alz­hei­mer’s dis­ease symp­toms.

The stu­dy’s lead au­thor owns stock in a com­pa­ny that could prof­it from the find­ings, and the sci­en­tists ac­knowl­edged that oth­er bi­ases could have col­ored the re­sults. None­the­less, the im­prove­ments in pa­tients with the no­to­ri­ously in­trac­ta­ble, mem­o­ry-erasing ill­ness were tested, widely no­ticed and are “wor­thy of fur­ther in­ves­ti­ga­t­ion,” they wrote in a pa­per on their re­sults.

Draw­ing of a cross-sec­tion of a typ­i­cal healthy brain (a­bove) com­pared to an Alz­hei­mer's-affected brain (be­low). (Cour­te­sy U.S. Nat'l Inst. on Ag­ing) 
The find­ings are of “sig­nif­i­cant sci­en­tif­ic in­ter­est,” added Sue Grif­fin, an­other Alz­hei­mer’s re­search­er. She is co-editor-in-chief of the Jour­nal of Neu­roin­flam­ma­t­ion, which pub­lished the study on­line Jan. 9. 

More than five mil­lion Amer­i­cans have the dev­as­tat­ing, fa­tal brain dis­ease, ac­cord­ing to the Alz­hei­mer’s As­socia­t­ion. The few ef­fec­tive treat­ments known gen­er­ally do lit­tle more than de­lay its pro­gres­sion.

By con­trast, the new ther­a­py, us­ing a drug al­ready ap­proved to treat oth­er ill­nesses, would seem to re­verse key Alz­hei­mer’s symp­toms with­in min­utes—though sci­en­tists aren’t speak­ing of a “cure” be­cause the treat­ment is­n’t ex­pected to hold off the ef­fects for­ev­er. 

The stu­dy, from the Un­ivers­ity of Cal­i­for­nia, Los An­ge­les and Un­ivers­ity of South­ern Cal­i­for­nia, fo­cused on a mol­e­cule called tu­mor ne­cro­sis fac­tor-al­pha, or TNF-al­pha, a crit­i­cal com­po­nent of the brain’s im­mune sys­tem. 

Nor­mal­ly, the mol­e­cule fine-tunes the trans­mis­sion of elec­tri­cal sig­nals in the brain. But ex­cesses of it seem to dis­rupt this reg­u­la­tory pro­cess in Alz­hei­mer’s, the re­search­ers said. They ex­plored the ef­fects of re­duc­ing lev­els of the mol­e­cule through in­jec­tions of a drug called etan­er­cept. The lead au­thor, Ed­ward To­bi­nick of UCLA, owns stock in Am­gen, the com­pany that makes the drug.

With­in min­utes of a spi­nal in­jec­tion of etan­er­cept (trade name En­brel), mol­e­cules of the drug latch on­to the TNF-alpha pro­tein, caus­ing it to stop work­ing, the re­search­ers said. Etan­er­cept is ap­proved by the U.S. Food and Drug Ad­min­is­tra­t­ion to treat cer­tain im­mune-re­lated dis­or­ders.

There has al­ready been con­si­der­a­ble buzz around the use of an­ti-TNF ther­a­peu­tics for var­i­ous dis­eases; the new find­ings jus­ti­fy some of that ex­cite­ment, the re­search­ers said. Grif­fin dis­cussed the re­sults and their im­plica­t­ions in a com­men­tary in the jour­nal along­side the re­search pa­per.

Al­though the pa­per it­self focuses on only one pa­tient, sci­en­tists said oth­ers with mild-to-severe Alz­hei­mer’s have al­so got­ten the treat­ment. There was “sus­tained and marked im­prove­ment” in each case, ac­cord­ing to an an­nounce­ment of the find­ings from the Un­ivers­ity of Ar­kan­sas for Med­i­cal Sci­ences, where Grif­fin con­ducts re­search. The state­ment al­so called the re­sults “dra­matic and un­prece­dent­ed.”

The stu­dy’s au­thors said some bi­ases could have crept in­to the out­comes. “All par­ti­ci­pants, in­clud­ing the ex­am­in­ing physi­cians, were aware of the treat­ment,” they wrote in the pa­per, which fo­cused on an 81-year-old doc­tor sick with Alz­hei­mer’s. This aware­ness could “bias the re­sults, and a pla­ce­bo ef­fect can­not be ruled out.” The pla­ce­bo ef­fect oc­curs when pa­tients feel bet­ter simply thanks to know­ing they’ve been treated.

How­ev­er, family mem­bers, friends and ob­jec­tive tests all at­test­ed to con­sider­a­ble im­prove­ments in the pa­tient’s mem­o­ry, they wrote. He went from not be­ing able to state the date, day of the week, year, place, city, or state, to be­ing able to give the day of the week, month, and state, Cal­i­for­nia. The im­prove­ments lasted for at least sev­en weeks with weekly treat­ment, wrote To­binick and his re­search col­league, Hy­man Gross of the Un­ivers­ity of South­ern Cal­i­for­nia.

How­ev­er, they not­ed, only some of Alz­hei­mer’s ef­fects are likely to be re­vers­i­ble, as struc­tur­al dam­age to brain cells even­tu­ally sets in for which there is no known cure.

None­the­less, “it is un­prec­e­dent­ed that we can see cog­ni­tive and be­hav­ior­al im­prove­ment in a pa­tient with es­tab­lished de­men­tia with­in min­utes” of treat­ment, Grif­fin said in the Un­ivers­ity of Ar­kan­sas ann­nounce­ment. “It is im­per­a­tive that the med­i­cal and sci­en­tif­ic com­mun­i­ties im­me­di­ately un­der­take to fur­ther in­ves­t­i­gate and char­ac­ter­ize the phys­i­o­lo­gic­al mech­a­nisms in­volved. This gives all of us in Alz­hei­mer’s re­search a tre­men­dous new clue about new av­enues of re­search, which is so ex­cit­ing and so needed.”

* * *

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In findings described as “dramatic and unprecedented,” researchers say they have found a treatment that leads to marked, sustained improvements in Alzheimer’s disease symptoms. The study’s lead author owns stock in a company that could profit from the findings, and the scientists acknowledged that other biases could have colored the results. Nonetheless, the improvements in patients with the notoriously intractable, memory-erasing illness were clearly tested, widely noticed and “worthy of further investigation,” they wrote in a paper on their findings. The findings are of “significant scientific interest,” added Sue Griffin, co-editor-in-chief of the Journal of Neuroinflammation, which published the report online Jan. 9. More than 5 million Americans have the devastating, fatal brain disease, according to the Alzheimer’s Association. The few effective treatments known generally do little more than delay its progression. By contrast, the new therapy, using a drug already approved to treat other illnesses, would seem to reverse some Alzheimer’s symptoms within minutes—though scientists aren’t speaking of a “cure” because the treatment isn’t expected to holds off the effects forever. The study, from the University of California, Los Angeles and University of Southern California, focused on a molecule called tumor necrosis factor-alpha, or TNF, a critical component of the brain’s immune system. Normally, the molecule fine-tunes the transmission of electrical signals in the brain. But excesses of it seem to disrupt this regulatory process in Alzheimer’s, the researchers said. They explored the effects of reducing levels of the molecule through injections of a drug called Etanercept. The lead author, Edward Tobinick of UCLA, owns stock in Amgen, which makes the drug. Within minutes of a spinal injection of Etanercept (trade name Enbrel), molecules of the drug latch onto the TNF protein, causing it to stop working, the researchers said. Etanercept is approved by the U.S. Food and Drug Administration to treat certain immune-mediated disorders. There has already been considerable buzz for some time around the use of anti-TNF therapeutics for various diseases; the new findings justify some of that excitement, the researchers said. Griffin discussed the results and their wider implications in a commentary in the journal alongside the research paper. Although the paper itself discusses only one patient, scientists said other patients with mild-to-severe Alzheimer’s have also gotten the treatment. There was “sustained and marked improvement” in each case, according to an announcement of the findings this week from the University of Arkansas for Medical Sciences, where Griffin conducts research. The statement also called the results “dramatic and unprecedented.” The study’s authors said some biases could have crept into the outcomes. “All participants, including the examining physicians, were aware of the treatment,” they wrote in the paper, which focused on the treatment of an 81-year-old doctor sick with Alzheimer’s. That could “bias the results, and a placebo effect cannot be ruled out.” The placebo effect occurs when patients feel better simply thanks to knowing they’ve been treated. However, family members, friends and objective tests all attested to considerable improvements in the patient’s memory, they wrote. He went from not being able to state the date, day of the week, year, place, city, or state, to at least being able to give the day of the week, month, and state (California.) The improvements lasted for at least seven weeks with weekly treatment, wrote Tobinick and his research colleague, Hyman Gross of the University of Southern California. However, they noted, only some of Alzheimer’s effects are likely to be reversible, as structural damage to brain cells eventually sets in for which there is no known cure. Nonetheless, “it is unprecedented that we can see cognitive and behavioral improvement in a patient with established dementia within minutes of therapeutic intervention,” Griffin said in the University of Arkansas annnouncement. “It is imperative that the medical and scientific communities immediately undertake to further investigate and characterize the physiologic mechanisms involved,” she continued. “This gives all of us in Alzheimer’s research a tremendous new clue about new avenues of research, which is so exciting and so needed in the field of Alzheimer’s. Even though this report predominantly discusses a single patient, it is of significant scientific interest because of the potential insight it may give into the processes involved in the brain dysfunction of Alzheimer’s.”