Bexarotene is an FDA-approved anti-cancer drug available under the brand name Targretin®. It clears Alzheimer’s biomarkers in mice like a charm. See the latest as it is rushed to human trials.
Alzheimer’s Drug Discovery Foundation (ADDF) and BrightFocus Foundation today announced a funding collaboration that will support a Phase I human clinical trial to evaluate the cancer drug bexarotene as a treatment for Alzheimer’s disease.
Through this partnership, the organizations are working to address a gap in funding that exists for these types of early stage studies. The trial will be conducted by ReXceptor Inc., a biotechnology company set-up by researchers at Case Western Reserve University (CWRU), and will examine the efficacy of bexarotene on key Alzheimer’s disease indicators, including brain amyloid beta and apolipoprotein E (apoE).
“This clinical trial will evaluate if bexarotene can affect critical biomarkers in the human brain, a key step in the quest to develop effective and safe treatments for Alzheimer’s patients,” said Howard Fillit , MD, executive director and chief scientific officer of the Alzheimer’s Drug Discovery Foundation. “We are grateful to BrightFocus Foundation for partnering with us to fund this important study.”
Bexarotene has been commercially available in the US for more than a decade as an orally administered treatment for T-cell lymphoma. Recently, Gary Landreth , PhD, the Riuko and Archie G. Co Professor of Neurosciences and Director of the Alzheimer’s Research Laboratory at CWRU’s School of Medicine, along with other researchers, demonstrated that bexarotene might also be useful in the treatment of Alzheimer’s disease. Landreth’s group showed that bexarotene increased brain apoE protein levels and cleared amyloid from the brain (a key target for Alzheimer’s disease) of mice genetically engineered to exhibit some of the characteristics of Alzheimer’s disease, which resulted in improved memory and cognition. To further advance bexarotene and related compounds through drug development, Dr. Landreth co-founded the biotechnology company ReXceptor in 2011.
“Funding for pilot clinical trials is in short supply,” said Stacy Pagos Haller , the president and chief executive officer of BrightFocus Foundation. “Partnering with another foundation in the community that shares a common goal makes research like this possible. In this time of shrinking corporate and pharmaceutical budgets, this project — from animal model to clinical trial — would not happen without the catalytic support of our organizations. The effort to cure Alzheimer’s disease needs many voices. This project demonstrates what can be achieved when a mission of one organization becomes a movement of many.”
Partial funding for ReXceptor Inc.’s trial includes The Charles Evans Foundation/Alzheimer’s Drug Discovery Award to ReXceptor Therapeutics of $500,000 and a $250,000 contribution from BrightFocus to the collaboration with ADDF. Additional funds are originating from other sources of translational support, including a $200,000 investment from CWRU, to enable conduct of the full Phase I study.
The Phase I trial, set to commence later this year, will evaluate at least 12 healthy human subjects. This study will be conducted by C2N Diagnostics and Compass Research, Inc. and will employ proprietary technology allowing the measurement of apoE and amyloid beta related biomarkers in the spinal fluid of individuals following treatment with bexarotene.
About the Alzheimer’s Drug Discovery Foundation (ADDF)
The mission of the Alzheimer’s Drug Discovery Foundation (ADDF) is to accelerate the discovery of drugs to prevent, treat and cure Alzheimer’s disease, related dementias and cognitive aging. The ADDF has invested nearly $60 million to fund 400 Alzheimer’s drug discovery programs and
clinical trials in academic centers and biotechnology companies in 18 countries. For more information, please visit www.AlzDiscovery.org
About BrightFocus Foundation
BrightFocus Foundation (formerly known as American Health Assistance Foundation) is a nonprofit organization supporting research and providing public education to help eradicate brain and eye diseases, including Alzheimer’s disease, macular degeneration, and glaucoma. We are working to save mind and sight. BrightFocus has provided $130 million in grants worldwide. For more information, please visit www.brightfocus.org
About ReXceptor Inc.
ReXceptor Inc. is focused on the development of disease modifying, small molecule therapeutics for the treatment of Alzheimer’s disease and other neurological disorders. The Cleveland, Ohio company was founded in 2011 based on work emanating from the laboratory of co-founder, Dr. Gary Landreth of Case Western Reserve University. For more information, please visit www.rexceptor.com
The text that I pasted bellow is from the site Dementia Today
However, the new reports from extensive and carefully controlled studies did not show any reduction in the number of plaques or total area occupied by the plaques during or after treatment. These results are described in three "technical comments" — one of which comes from researchers at the University of Chicago, Northwestern University, Massachusetts General Hospital, Washington University in St Louis and University of Tubingen in Germany — to be published in the May 24, 2013, issue of Science.
"The drug has no impact on plaque burden in three strains that exhibit Aβ amyloidosis," according to that group's comment. "We have failed to support earlier findings by Cramer et al that Targretin is efficacious in reducing plaque burden in transgenic mouse models of cerebral Aβ deposition."
Comment 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 these results presented at a small conference," said Sisodia. "The mechanism of action made some sense, but the assertion that they could reduce the areas of plaque by 50 percent within three days, and by 75 percent in two weeks, seemed too good to be true."
"We all went back to our labs and tried to confirm these promising findings," Sisodia added. "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 in three different strains of mice that 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: treatment of refractory cutaneous T-cell lymphoma, a type of skin cancer. Once approved, the drug became legally available by prescription for "off-label" uses as well.
"Anecdotally, we have all heard that physicians are treating their Alzheimer's patients with bexarotene, a cancer drug with severe side effects," said co-author Robert Vassar, PhD, professor of cell and molecular biology at Northwestern University Feinberg School of Medicine. "This practice should be ended immediately, given the failure of three independent research groups to replicate the plaque-lowering effects of bexarotene."
Bexarotene has never been tested as a treatment for Alzheimer's disease in humans, not even to determine the optimal dose or duration of treatment. This drug has significant side effects, including major blood-lipid abnormalities, pancreatitis, liver function test abnormalities, thyroid axis alterations, leucopenia, headaches, fatigue, weight gain, depression, nausea, vomiting, constipation and rash.
The text that I pasted above is from the site dementia today
So what happens to the Phase I trial in humans? I hope it gets done anyhow, unless folks think that the initial murine study was fraudulent Dementia is a horror-show with radiating aspects that are hard to appreciate unless one has a relative who is experiencing it.
Carlos' comments only paint half the picture. Given the whole picture, it is clear the clinical trials will continue. For the whole picture, read the article,
Bexarotene for Alzheimer's: The Good, the Bad and the Ugly
Bexarotene for Alzheimer's: The Good, the Bad and the Ugly
Hope these could be the cure for these disease,
@michael if things didn't go work well on the phase I they will try another one as long as the clinical trial have enough funding this is how clinical trials work.
I would like info on my area as to volunteers Norfolk va ed kerr
Check out the United States government's centralized website, http://www.clinicalTrials.org