In a darkened room at Toronto’s Krembil Research Institute, Dr. Donald Weaver is looking at a screen covered in green fluorescent dots.
That’s not a good thing.
Those glowing green dots are exactly what this Alzheimer’s researcher did not want to see.
“Weeks if not months of work went into this compound and it failed,” he said. “It’s done.”
Weaver, a neurologist and chemist, was testing a compound to see if it could prevent the clumping of a protein called tau which creates distinctive tangles in the brains of people with Alzheimer’s disease.
This is a disease in which so many approaches have failed. – Dr. Donald Weaver, Krembil Research Institute
If it had worked, it might have been a candidate for a new drug.
But it didn’t work, just like the thousands of others he’s already tried.
Failure is normal for researchers engaged in the frustrating search for drugs to treat Alzheimer’s disease.
“You have to be passionate,” Weaver said. “This is a disease in which so many approaches have failed. You really have to deeply believe that your approach is correct just to get up every day and keep working at it.”
But after a series of high-profile drug failures over the past few years, scientists are facing the disturbing possibility that their leading theory of Alzheimer’s might be fatally flawed.
It’s called the amyloid hypothesis, and it was an obvious target for researchers because the amyloid protein forms distinctive plaques in the brains of people with Alzheimer’s.
“That led to the conclusion it must be playing a pretty important role in the disease,” Weaver said.
The amyloid hypothesis was first proposed in 1992, and for the past 25 years research has focused on finding compounds that clear amyloid from the brain or slow down its production.
But one by one they’ve been dropped because they don’t change the outcome for people with Alzheimer’s disease.
Some argue that the drugs are being given too late — that the amyloid damage has already advanced too far.
But some scientists believe it’s time to declare the amyloid hypothesis “dead” and move on to other ideas.
It is possible that everything has been sort of built on a shaky foundation all along.– Paul Murphy, University of Kentucky
At the University of Kentucky, Paul Murphy is one researcher who will say it aloud.
“It would be foolish to ignore the continued failures of anti-amyloid approaches,” Murphy wrote in a controversial editorial in the New England Journal of Medicine in January.
“The field is clearly in need of innovative ideas. We may very well be nearing the end of the amyloid-hypothesis rope, at which point one or two more failures will cause us to loosen our grip and let go.
“It is possible that everything has been sort of built on a shaky foundation all along, and we won’t know that for a few years,” Murphy told CBC News.
The list of unknowns about Alzheimer’s is long. Scientists still don’t know exactly what causes the disease. They don’t know what amyloid’s function is or why the body produces it.
And they don’t know what would happen if they could prevent amyloid from accumulating in the brain years before any symptoms appear.
“By 2020, we [will] probably have a good idea if that is working or not,” said Murphy. If the results show that people still get the disease even though drugs have prevented amyloid deposits, then the amyloid hypothesis could suffer a fatal blow.
“If you asked me five years ago is the amyloid hypothesis true or not, I would have said absolutely,” Murphy said. “But now, after a lot more clinical failures, you really have to start to wonder have we really gone down the wrong path.”
Over the past few years, many of the most promising drugs have failed in clinical trials. The latest disappointment came on Friday when Janssen announced it was ending clinical trials of one drug — the BACE inhibitor atabecestat —because of liver toxicity.
And in January, Pfizer, one of the world’s largest pharmaceutical companies, announced it was ending its Alzheimer’s research program
“Personally, I am disappointed that some companies are walking away from it, because it is such a huge unmet need,” Weaver said. “It requires the pharmaceutical sector to push it over the goal line, and the fewer companies we have doing it, the more challenging that is going to become. But given the expense and given the failure rate, I understand why they make the decisions that they are making.”
As hope for the amyloid hypothesis fades, scientists are following other leads.
Back in Toronto, Weaver has developed a computer model that will screen thousands of compounds searching for activity with both amyloid and tau. He’s come up with some promising compounds and he’s working with a French pharmaceutical company to develop them.
At his lab in Kentucky, Murphy is investigating links between Alzheimer’s and cerebral vascular disease. Other research targets include neuroinflammation, mitochondrial misfunction, a class of brain cells called “microglia,” and the role of reactive oxygen species, also called “free radicals.”
“Now is the time to start thinking about totally different things that we haven’t undertaken that people thought sort of might be interesting but haven’t really tried yet,” Murphy said.
Read more here: CBC | Health Newshappy wheels
Jan 22, 2019 0Future and his baby mama drama have created just as many headlines as his music in recent years, partially because he hasn’t dropped much until this week. Now he’s doing a press run for his new LP and sat down with Hot 97’s Nessa to speak about things going on in his life. When the […]
Jan 21, 2019 0
Jan 22, 2019 03 hours ago If you saw Glass during opening weekend, you may already know that James McAvoy really worked out before and during the movie’s filming to get into beast mode. He’s previously talked about his insane workouts, but recently James McAvoy revealed his motivation for getting...
Jan 21, 2019 0Januhairy Is Here, and Women Are Taking to Instagram to...
Jan 20, 2019 0Retin-A Side Effects and Benefits for Anti-Aging and Acne...
Jan 20, 2019 0This Woman Credits Drunk Elephant Skin Care Products for...
Jan 20, 2019 0The Best Chocolate Lilac Hair Styles – Health Top...
Jan 22, 2019 0After her Brexit plan went down to the most resounding...
Jan 22, 2019 0CARACAS, Venezuela — Members of the Venezuelan National...
Jan 22, 2019 0KABUL, Afghanistan — The Taliban infiltrated an Afghan...
Jan 21, 2019 0ANKARA, Turkey — After lengthy meetings with the Turkish...
Jan 21, 2019 0TAIPEI, Taiwan — Just a few weeks ago, President Tsai...
Jan 21, 2019 0ROSARITO, Mexico — On a forlorn beach, a long line of...
Jan 21, 2019 0GDANSK, Poland — In a bitterly divided Poland, residents...
Jan 20, 2019 0ROME — More than 100 African migrants who set off in a...
Jan 20, 2019 0LONDON — In the wretched purgatory that was Westminster...
Jan 20, 2019 0TLAHUELILPAN, Mexico — Mexico’s president vowed on...