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June 28, 2017

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Failure of Alzheimer's drugs points to new cure possibilities

WASHINGTON--After the failure of two novel drugs using antibodies to fight the buildup of brain plaque in Alzheimer's patients, scientists said Wednesday they have learned lessons for the future.

The biologic drugs solanezumab, by pharmaceutical giant Eli Lilly, and bapineuzumab, by Johnson & Johnson, made it to phase III trials and were taken by thousands of patients, according to a full report on the research published in the New England Journal of Medicine.

However, neither succeeded in improving the cognitive function of patients in the study when compared to a sugar pill.

News of the drugs' failure first broke in 2012, stunning the research community and dashing the hopes of millions worldwide whose relatives suffer from the incurable form of dementia.

"The biggest disappointment from this trial was that if we had shown benefit with a drug like bapi, it would give people hope that Alzheimer's is a treatable disease, that we can slow it down," said lead researcher Stephen Salloway, professor of neurology and psychiatry at Brown University's Warren Alpert Medical School.

Looking back at the data, researchers learned that as many as 25 percent of the people they were studying likely did not have Alzheimer's disease but some other form of dementia, since they did not have a significant amount of amyloid plaque buildup in their brains.

Future trials should enroll only patients who are confirmed to have Alzheimer's with a PET scan and spinal fluid testing, Salloway said.

Getting the medication to patients earlier in the progression of their disease could also produce more tangible effects, he said.

Another approach could be to pair antibody drugs with drugs such as a beta secretase inhibitor that maximize amyloid lowering, he said, though the safety of such combinations is unknown and would require thorough testing.

"Alzheimer's is a difficult and complex disease, and we are moving forward," said Salloway.

An accompanying editorial by doctors at University College London and Alzheimer's Research UK said the two trials "provided valuable information."

Even though the trials and their failures raised questions about the role played by amyloid beta proteins that form harmful plaques in the brains of Alzheimer's patients, more research should continue in this area, the editorial urged.

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