Bexarotene for Alzheimer’s: The Good, the Bad and the Ugly ;
The last month has been full of news about bexarotene for Alzheimer’s is good, bad, and ugly.
researchers Pitt Public Health were able to verify that bexarotene not significantly improve cognitive deficits in mice expressing mutations of genes related to Alzheimer’s disease human.
This reproduces the results of 2012, which bexarotene improved memory and cognition in Alzheimer’s disease.
These positive results were lost in the din of news articles on studies showing that bexarotene not last year’s results replicated with regard to cleaning of plaque in mice with Alzheimer’s. This was very surprising because the great welcome that bexarotene did in the Alzheimer scene last year was based on his memory improve mainly in cleaning Alzheimer’s plaques.
How can integrate these new results were better explained in an interview with Dr. Ronald Peterson , which represents the highest part of Alzheimer’s research in the United States, as head of the PNA and the director of Alzheimer’s research at the Mayo Clinic. He said:
“While the overall tone is that I have four documents not replicate the results (last year) original, there are elements of these documents, in fact, make reproduce his results
. “So, in particular, some of the enhanced in some of the animals that were tested in other studies, and a particular form of amyloid behaviors (the so-called soluble amyloid, or oligomeric form of the amyloid) , it was in fact replicated in other roles.
“I mean, some features were not (replicated), but in general, the basic premise was repeated. ”
In a second round of good news this week, researchers at Cambridge published the results of a long-term study demonstrating the centrality of soluble damage behind Alzheimer’s disease oligomers.
Cambridge This study may explain how bexarotene works in the fight against Alzheimer’s disease.
Furthermore, if the test bexarotene to clear these oligomers and also passes clinical trials, it could be compelling evidence that researchers at Cambridge have every right conclusions about Alzheimer’s disease.
Cambridge studying copy of bexarotene security, and bexarotene studies back up the findings of Cambridge?
In our report on bexarotene last week, one of our readers summary “bad news” on bexarotene in the comments section as follows:
new reports of extensive studies and carefully controlled showed no reduction in plaque number or total area occupied by the plates during or after treatment.
These results are described in three “technical comments” – one of whom come from researchers at the University of Chicago, Northwestern University, Massachusetts General Hospital, Washington University in St. Louis and the University of Tubingen in Germany – which will be published in the edition of May 24, 2013, issue of Science.
“the drug has no impact on plaque burden in three strains exhibiting Aß amyloidosis,” according to the commentary of that group.
“We have failed to support earlier findings by Cramer et al that Targretin is effective in reducing plaque burden in transgenic mouse models of cerebral Aß deposition.”
Commentary co-author Sangram Sisodia, PhD, professor of neurosciences at the University of Chicago, said he and his colleagues were curious about the initial report in 2012.
“we were surprised and excited, even stunned when we first saw the results presented in a small conference, “Sisodia said.
“The mechanism of action made some sense, but the claim that could reduce plaque areas by 50 percent within three days, and 75 percent in two weeks, it seemed too good to be true. ”
“everyone headed back to our labs and try to confirm these promising results,” added Sisodia
“we repeat the initial experiments – .. a standard process in science combined results are really important in this field.
None of us are nothing like what was described in 2012. “
researchers found no effect on plaque burden in three different strains of mice They were treated with bexarotene.
The discrepancy, besides being disappointing, also raises concerns about patient safety. The Food and Drug Administration approved bexarotene in December 1999 for a very specific use: the treatment of cutaneous T-cell lymphoma refractory, a type of skin cancer. Once approved, the drug became legally available prescription for “off-label” uses.
“Anecdotally, we’ve all heard that doctors are treating patients their Alzheimer bexarotene a cancer drug with serious side effects,” said co-author Robert Vassar, PhD, professor of cell biology and molecular Northwestern University Feinberg School of Medicine. “This practice must end immediately, given the failure of three independent research groups to replicate the effects of bexarotene plate decreased.”
Bexarotene has never been tested as a treatment for Alzheimer’s disease in humans, or even to determine the dose or duration of optimal treatment.
This drug has significant side effects, including major lipid abnormalities in the blood, pancreatitis, abnormal tests of liver function, abnormal thyroid axis, leucopenia, headaches, fatigue, weight gain, depression, nausea, vomiting, constipation and rash.
Dr. Peterson feels there is still a valid “basic premise” that bexarotene certainly helps memory in mice with Alzheimer’s.
Dr. Landreth, who made the initial discovery in 2012, has begun a clinical trial with 12 people, to study whether bexarotene accelerates the clearance of soluble oligomers in humans, as it did in mice.
Scientists at the University of Leuven in Belgium reported some improvements in memory in mice treated. However, they warned that “given the toxicity of bexarotene, our study clearly warns strongly against testing the drug in patients at this time.”
Another team, led by Rada Koldamova at the University of Pittsburgh, which bexarotene cognitive improvement is mice.The problems in mice were given a challenge memory, and a spatial test they have to find a hidden platform in a water maze. The “Alzheimer’s mice” performed as well as normal mice 10 days after starting treatment.
“I was not too disappointed when we do not see the effect of the drug on plates,” said Dr. Koldamova. “There are other beneficial elements” that support the continued study of bexarotene for Alzheimer’s. “
This article was originally published on alzheimersweekly, Read the original article here