Alzheimer's 'wonder drug' could be completely ineffective, warn scientists



Research had implied cancer drug Targretin improved Alzheimer's symptoms

Tests on mice showed it reversed brain plaque build-up linked to Alzheimer's

Some doctors at the time had questioned the 'too good to be true' results

Was given to some patients 'off label' despite not being tested for dementia

New research now suggests it has no effect on plaque build-up



The cancer drug bexarotene, marketed as Targretin, was said to reverse the build-up of the brain plaques which have been linked Alzheimer's

A 'wonder' drug hailed as a new treatment for Alzheimer's may be ineffective, experts have warned.



The cancer drug bexarotene, marketed as Targretin, was said to reverse the build-up of the brain plaques which have been linked Alzheimer's.



A high profile 2012 report, published in journal Science, reported that the drug quickly removed most of the plaques in the brains of mice and rapidly reversed the pathological, cognitive and memory deficits related to the onset of Alzheimer's.



The results were 'stunning' to the scientific community but seemed 'too good to be true', it was claimed at the time.



Now, another team of experts writing in the same journal say they have been unable to replicate the results of the original study and have called the findings into doubt.



Researchers at the University of Chicago, Northwestern University, Massachusetts General Hospital, Washington University in St Louis and University of Tubingen in Germany, jointly stated: ‘The drug has no impact on plaque burden.



‘We have failed to support earlier findings that Targretin is efficacious in reducing plaque burden in transgenic mouse models of cerebral plaque deposition.’



Professor Sangram Sisodia, of the University of Chicago, said he and his colleagues were curious about the initial report in 2012.



He said: ‘We were surprised and excited, even stunned, when we first saw these results presented at a small conference.

‘The mechanism of action made some sense, but the assertion that they could reduce the areas of plaque by 50 per cent within three days, and by 75 per cent in two weeks, seemed too good to be true.

‘We all went back to our labs and tried to confirm these promising findings.



‘We repeated the initial experiments - a standard process in science. Combined results are really important in this field. None of us found anything like what they described in the 2012 paper.’



The researchers found no effects on plaque burden of mice that were treated with bexarotene.



They say that the discrepancy is not only disappointing but also raises concerns for patient safety.

The drug was approved for treating a type of skin cancer, meaning it is also available by prescription for 'off label' uses as well.

But is has never been tested as a treatment for Alzheimer's in humans and has side effects including headaches, vomiting and liver problems.

New research suggests that the drug, which has severe side effects, has no effect upon the plaques which cause Alzheimer's symptoms. Image shows CT scans of the brain of an Alzheimer's patient

Despite the lack of testing on Alzheimer’s patients, it is believed that many requested that their doctors prescribed them the medication and, in some cases, were given it.



Professor Robert Vassar, of Northwestern University, said: ‘Anecdotally, we have all heard that physicians are treating their Alzheimer's patients with bexarotene, a cancer drug with severe side effects.



‘This practice should be ended immediately, given the failure of three independent research groups to replicate the plaque-lowering effects of bexarotene.’



But other experts, also writing in Science, said that the cognitive effects on the mice had been replicated, even if the effects on plaque had not.



University of Pittsburgh professor, Rada Koldamova said that the drug did improve cognitive effects on mice, although tests could not confirm the actual effects on the plaques.



Professor Koldamova said: ‘We believe these findings make a solid case for continued exploration of bexarotene as a therapeutic treatment for Alzheimer's disease.’



Co-author Iliya Lefterov said: ‘We were already set up to repeat the Case Western Reserve University study to see if we could independently arrive at the same findings.

