Health and Healthcare Systems

Alzheimer's treatments are failing us. Here's why we need a new approach

Plaster phrenological models of heads, showing different parts of the brain, are seen at an exhibition at the Wellcome Collection in London March 27, 2012.  We've pickled it, dessicated it, drilled it, mummified it, chopped it and sliced it over centuries, yet as the most complex entity in the known universe, the human brain remains a mysterious fascination. With samples of Albert Einstein's preserved brain on slides, and specimens from other famous and infamous heads such as the English mathematician Charles Babbage and notorious mass murderer William Burke, an exhibition opening in London this week is seeking to tap into that intrigue. The exhibition Brains: The Mind As Matter runs from March 29 to June 17. REUTERS/Chris Helgren       (BRITAIN - Tags: SCIENCE TECHNOLOGY SOCIETY HEALTH) - RTR2ZYK1

Alzheimer's affects nearly 5 million Americans, a number that's expected to balloon to 13.8 million by 2050 . Image: REUTERS/Chris Helgren

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Alzheimer's affects nearly 5 million Americans, a number that's expected to balloon to 13.8 million by 2050 .

The search for a treatment hasn't been going well. There are only four approved drugs that treat the symptoms of the disease, and several hopeful treatments have failed key studies over the last few months.

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Image: Reuters

The recent failures have people contemplating what went wrong — and if it's time to reevaluate how we treat the disease.

One theory people keep coming back to: We might be trying to treat the neurodegenerative disease at the wrong time, when it's too late.

"If you have to wait to start treating when people have symptoms, it's probably too late to have a significant impact," Dr. Matthew Fink, chairman of Neurology at Weill Cornell Medicine told Business Insider in January.

Why starting early could be key

Research has determined that years — even decades — before a person might start showing symptoms, amyloid beta deposits in the brain that are characteristic of Alzheimer's disease can start to accumulate.

There's a simple explanation to why treating these conditions early might be more successful than waiting to treat until a person has symptoms. Here's how Newsweek explained it:

"What’s happening in this early stage of Alzheimer’s can be likened to the kindling that starts a house fire. Amyloid plaques slowly smolder for years, consuming the neuronal tinder in our brains. By the time dementia kicks in, the fire is raging and it’s too late to save the house. Calling in firefighters at that point is a waste of time and money. You need to dial 911 at the first signs of smoke—and the same could be true of when to deliver anti-amyloid drug therapies."

So preventing any progression at that stage is something researchers are pinning a lot of hope on. Newsweek cites five clinical trials that are in the works to determine whether starting early, years before symptoms show up, is the best approach to treating the disease.

Fink pointed to one in particular, going on in Colombia, that's testing out an amyloid-related drug in an extended family with a rare genetic mutation that leads to early-onset Alzheimer's. That study is in people who are still considered cognitively healthy, so if the drug is able to prevent cognitive decline, it could be a breakthrough.

"We're all pinning a lot of hopes on the results of that test," he said.

Holding out hope for the 'amyloid hypothesis'

Starting earlier could benefit treatments that are targeting beta amyloid deposits in the brain, with the hope that clearing them out could help slow down the rate of cognitive decline. A number of the drugs that have failed in recent trials fall under that so-called "amyloid hypothesis."

Most recently, on February 15, drugmaker Merck stopped its late-stage trial of its drug, verubecestat, in patients with mild to moderate Alzheimer's, after a committee found that there was "virtually no chance of finding a positive clinical effect." The hope was to have the drug stop the disease from progressing. Merck said it's still working on another late-stage trial for the drug to treat people with even earlier stages of the disease, and those results are expected in 2019.

But there's one major drawback to the amyloid-beta approach: In people who have Alzheimer these deposits build up in certain parts of the brain, but it's still not known whether the plaques cause the disease, or are just a byproduct. What does seem to be well established is that in people with the genetic version of the disease, there is a strong relationship between those mutations and amyloid plaques.

The other trial Merck's continuing, where they're targeting people with even earlier stages of Alzheimer's. And treating as early as possible could be the key to proving out the amyloid hypothesis, Roger Pelmutter, Merck's head of research and development told Forbes.

There will be more opportunities to see that hypothesis in action, too. Biogen, another company that's big in neuroscience, expects to have data on its beta-amyloid targeting treatment in 2019.

Dr. Larry Altstiel, chief medical officer at VTV Therapeutics told Business Insider that he's still a believer in the amyloid hypothesis. But, he said, the approach might be a bit too narrow. VTV has an Alzheimer's drug in late-stage trials called azeliragon that inhibits the RAGE receptor and in part goes after that amyloid-beta, ideally helping people with mild Alzheimer's delay cognitive decline.

"Is it sufficient to address one at the expense of others? I think it remains to be seen," He said. "Everybody's saying a-beta hypothesis is dead. it's not dead. It's just, are the drugs treating A-beta going to be enough?"

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