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posted by janrinok on Friday February 16 2018, @10:12PM   Printer-friendly [Skip to comment(s)]

Merck has ended a trial for the experimental Alzheimer's treatment verubecestat, a BACE1 inhibitor, after it was found to be ineffective. Biogen has increased the sample size of a trial for aducanumab, worrying some investors. The news comes after the failure of drugs such as solanezumab and intepirdine to treat Alzheimer's and dementia.

The FDA has proposed new guidelines that would make it easier to treat Alzheimer's by lowering the bar for clinical success:

In proposed new guidelines released on Thursday, the FDA appears open to trial goals that better match early patient populations, including people who have yet to display memory loss or functional impairment, such as the ability to wash or dress themselves or cook meals.

The draft guidelines suggest that improvement in biomarkers, such as amount of beta amyloid in the brain, a protein linked to the disease, may be an acceptable goal for deeming a drug successful in patients with no symptoms. FDA guidelines used in prior studies demanded that a drug demonstrate both cognitive and functional improvements.

A bipartisan group of Senators and Congressman have introduced the Concentrating on High-Value Alzheimer's Needs to Get to an End (CHANGE) Act, which would also reduce regulatory barriers faced by clinical trials. The annual cost of Alzheimer's and dementia care in the U.S. is projected to rise to $1.1 trillion by 2050.

Meanwhile, a group of researchers has found that targeting BACE1 enzymes could remove existing amyloid plaques (in mice):

Knocking back an enzyme swept mouse brains clean of protein globs that are a sign of Alzheimer's disease. Reducing the enzyme is known to keep these nerve-damaging plaques from forming. But the disappearance of existing plaques was unexpected [open, DOI: 10.1084/jem.20171831] [DX], researchers report online February 14 in the Journal of Experimental Medicine.

The brains of mice engineered to develop Alzheimer's disease were riddled with these plaques, clumps of amyloid-beta protein fragments, by the time the animals were 10 months old. But the brains of 10-month-old Alzheimer's mice that had a severely reduced amount of an enzyme called BACE1 were essentially clear of new and old plaques.

An Alzheimer's treatment, donepezil, has been used to treat alcohol-related brain damage in mice.

Finally, a study of eight patients with cerebral amyloid angiopathy (CAA), a brain bleeding condition, found that all eight had undergone brain surgery earlier in life, suggesting that insufficiently clean surgical instruments could spread amyloid proteins from one person to another and cause CAA:

None of these people have known gene variants that would raise the risk of developing CAA early. [Sebastian] Brandner's team says the most likely explanation is that amyloid proteins were seeded into their bodies during childhood brain surgery, from instruments previously used for surgeries on people with Alzheimer's disease. Creutzfeldt-Jakob Disease (CJD), a brain disease caused by prion proteins, is already known to have been spread in a similar way.

Evidence of amyloid-β cerebral amyloid angiopathy transmission through neurosurgery (open, DOI: 10.1007/s00401-018-1822-2) (DX)

Original Submission

Related Stories

Failure of Promising Alzheimer Drug Strikes a Blow to Theory 17 comments

The amyloid hypothesis is the theory that the accumulation of beta-amyloids in the brain leads to Alzheimer's Disease. These amyloids are "sticky" protein fragments, and the idea is that something in the body that normally regulates them fails and they accumulate in the brain. The idea was proposed in the early 1990s when it was observed that many Alzheimer's patients exhibited larger than normal amounts of amyloid plaques. This hypothesis has driven a very active area of research for drugs and treatments that address beta-amyloids.

In what some see as a fundamental blow to the hypothesis itself, it was recently announced that one of the leading drugs, solanezumab from Eli Lilly, has failed in a large trial of people with mild dementia. The clinical trial involved more than 2,100 people diagnosed with mild dementia due to Alzheimer’s disease, but the results showed only a small benefit of the drug. Eli Lilly has also been conducting prevention trials where the drug is given to people known genetically to be high-risk for the disease, and they said they will discuss with their clinical trial partners whether they will continue those studies.

Lilly’s result may say more about the characteristics of solanezumab than the accuracy of the underlying amyloid hypothesis, says Christian Haass, head of the Munich branch of the German Centre for Neurodegenerative Diseases. The antibody targets soluble forms of amyloid, he points out, so it “could be trapped in the blood without ever reaching the actual target in the brain in sufficient quantities”.

The appeal of the amyloid hypothesis is that it is a simple one. However, in the 25 years since it was proposed, it has led to essentially no progress in preventing or curing the disease. Criticism of the theory has grown with each failed result.

“We’re flogging a dead horse,” adds Peter Davies, an Alzheimer’s researcher at the Feinstein Institute for Medical Research in Manhasset, New York. “There’s no sign of anybody getting better, even for a short period, and that suggests to me that you have the wrong mechanism.”

Original Submission

Pfizer Halts Research Into Alzheimer's and Parkinson's; Axovant Sciences Abandons Intepirdine 11 comments

Pfizer has announced that it will halt efforts to find new treatments for Alzheimer's and Parkinson's diseases. Meanwhile, Axovant Sciences will halt its studies of intepirdine after it failed to show any improvement for dementia and Alzheimer's patients. The company's stock price has declined around 90% in 3 months:

Pfizer has announced plans to end its research efforts to discover new drugs for Alzheimer's and Parkinson's diseases. The pharmaceutical giant explained its decision, which will entail roughly 300 layoffs, as a move to better position itself "to bring new therapies to patients who need them."

"As a result of a recent comprehensive review, we have made the decision to end our neuroscience discovery and early development efforts and re-allocate [spending] to those areas where we have strong scientific leadership and that will allow us to provide the greatest impact for patients," Pfizer said in a statement emailed to NPR.

[...] Despite heavily funding research efforts into potential treatments in the past, Pfizer has faced high-profile disappointment in recent years, as Reuters notes: "In 2012, Pfizer and partner Johnson & Johnson (JNJ.N) called off additional work on the drug bapineuzumab after it failed to help patients with mild to moderate Alzheimer's in its second round of clinical trials."

Another potential treatment for neurodegenerative disorders — this one developed by Axovant, another pharmaceutical company — also found itself recently abandoned. The company dropped its experimental drug intepirdine after it failed to improve motor function in patients with a certain form of dementia — just three months after it also failed to show positive effects in Alzheimer's patients.

Looks like GlaxoSmithKline got a good deal when they sold the rights to intepirdine to Axovant Sciences in 2014.

Also at Bloomberg.

Related: Can we Turn Back the Clock on Alzheimer's?
Possible Cure for Alzheimer's to be Tested Within the Next Three Years
Mefenamic Acid Might Cure Alzheimers - Generic Cost in US is Crazy
New Alzheimer's Treatment Fully Restores Memory Function in Mice
Power Outage in the Brain may be Source of Alzheimer's
Another Failed Alzheimer's Disease Therapy
The FDA Saved Taxpayers from Paying Billions for Ineffective Alzheimer's Therapy
Alzheimer's Disease: A "Whole Body" Problem?
Bill Gates Commits $100 Million to Alzheimer's Research
Evidence That Alzheimer's Protein Spreads Like an Infection

Original Submission

Disputed Alzheimer's Study Links Decrease in Amyloid Levels to Reduction in Cognitive Decline 4 comments

Alzheimer's study sparks a new round of debate over the amyloid hypothesis

In the long-running debate over just what causes Alzheimer's disease, one side looks to have scored a victory with new results with an in-development drug. But there's enough variation in the data to ensure that the squabbling factions of Alzheimer's will have plenty to fight about.

At issue is the so-called amyloid hypothesis, a decades-old theory claiming that Alzheimer's gradual degradation of the brain is caused by the accumulation of sticky plaques. And the new drug is BAN2401, designed by Biogen and Eisai to prevent those amyloid plaques from clustering and attack the clumps that already have.

In data presented last week, one group of patients receiving BAN2401 saw their amyloid levels plummet, a result that was tied to a significant reduction in cognitive decline compared with placebo.

[...] But to skeptics, the trial was laden with confounding details that make it impossible to draw conclusions. "These results are a mess," wrote Baird biotech analyst Brian Skorney. "Not so much that they indicate an outright failure of the [amyloid] hypothesis, but they don't really say anything informative at all."

Related: Alzheimer's Disease: A "Whole Body" Problem?
Evidence That Alzheimer's Protein Spreads Like an Infection
Pfizer Halts Research Into Alzheimer's and Parkinson's; Axovant Sciences Abandons Intepirdine
Positive Result in Mice as Alzheimer's Drug Trials Fail and Regulatory Barriers Are Rolled Back

Original Submission

FDA Approves New Treatment for Alzheimer's Disease 20 comments

The FDA has approved a new drug for Alzheimer's disease, while not a cure it is supposed to slow the decline. Even though data is not entirely positive or straight forward in its interpretation or that it will actually even work as thought.

But if you have it then you are probably desperate enough to try almost anything that claims to work, until you get to the price tag of $56,000 per year. That will probably make it out of reach for most people, it's doubtful if any insurance will cover something like this. Perhaps you can just forget to pay the bill, they might understand due to your condition.

Biogen CEO Michel Vounatsos [...][said] he thought the drug's price was "fair" but also vowed that the company would not hike its price for four years.

In Surprise Turnaround, Biogen to Submit Previously Failed Alzheimer Drug for Approval
Disputed Alzheimer's Study Links Decrease in Amyloid Levels to Reduction in Cognitive Decline
Positive Result in Mice as Alzheimer's Drug Trials Fail and Regulatory Barriers Are Rolled Back

Original Submission

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  • (Score: -1, Spam) by Anonymous Coward on Friday February 16 2018, @10:30PM

    by Anonymous Coward on Friday February 16 2018, @10:30PM (#639086)

    It's in. Your rancid hole sucked my fetid little friend right into it as if your nasty asshole was a spaghetti noodle! I guess I'll have to return the favor by shooting my little white tadpole friends straight into your feces-filled rectal womb! Ahhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhh, too good! I'm going to force your rectal womb to give birth to my feces babies one after another until it's broken! Get pregnant! Get pregnant! Get pregnant!!!!!!!!!!!!!!!!!!!!!

  • (Score: 4, Insightful) by fadrian on Saturday February 17 2018, @12:28AM (3 children)

    by fadrian (3194) on Saturday February 17 2018, @12:28AM (#639135) Homepage

    For your money, you get a drug that won't actually help you in any functional way - just a reduction in a number that has only a tenuous relationship to the actual disease progression. Sounds like quite a deal! Well, at least for the drug companies. Quite a regulatory coup for our intrepid swamp drainers. Thanks, Trump!

    That is all.
    • (Score: 4, Interesting) by sonamchauhan on Saturday February 17 2018, @01:41AM (1 child)

      by sonamchauhan (6546) on Saturday February 17 2018, @01:41AM (#639156)

      No really. If it hinders disease progression, this may be a good thing. For any drug to demonstrate cognitive and functional improvements when the brain is severely damaged already is a tall order.

      But I agree amyloid plaque reduction should not be the only measure. We probably need more sensitive tests that measure the earliest signs of disease progression (eg, measure the trend in gamma waves, reaction times, tough cognitive tests, etc).

      And recruiting the body's own cleanup tools should be a priority. Two that I know of are below.

      A. Sound, flickering light and movement, all at 40Hz, is known to generate gamma waves in the brain that cleanup amyloid plaques.

      A.1. For light, see: [] []

      A.2. For sound: [] [] [] []

      A.3. For movement: use a vibration platform.
      To find what machine setting (typically 1,2,3..) corresponds to 40Hz, I did something very simple. Starting at '1', I put my finger just above the platform and counted the 'up-down-up' beats in a set interval to get the rate. Then I did the same thing with '2'. Then extrapolated. My machine setting was '13'.

      B. Using ultrasound and injected microbubbles to temporarily open up the blood-brain-barrier (BBB).

      In mice, their own immune system then cleared up brain plaques: [] []
      "The effect seems to be related to mild disruption of the blood brain barrier which allows the immune system to clean up the extracellular protein aggregates more effectively than otherwise possible."

      A clinical trial is underway in Canada to use ultrasound to deliver anti-amyloid antibodies to the brain: [] [] []

      Interestingly, the BBB is already compromised in many Alzhiemer's patients. Its unclear to me if this is a cause or effect or fellow-traveller of Alzhiemer's disease.
      "Blood–brain barrier dysfunction as a cause and consequence of Alzheimer's disease" []

      At some point, I even wondered about an 'ultrasound-cleaner' device I have (the type used to clean jewellery). Could it be used with a water-filled bag to 'treat' a neighbour's dog that had dementia. Picture the dog lying on its side, with a water bag to the back of its head, and the cleaner device on the other side. I did not followed through.

      C. A skin cancer drug, Bexarotene, helps certain people if prescribed off-label for Alzheimer's [] []

      I think a full-spectrum approach is needed. All therapies should be tried - in conjunction - if likely to synergize instead of cause harm. For instance, Bexarotene decreases BBB permeability but its mechanism of action may be autophagy. []

      D. Excess sugar may cause Alzhiemer's []

      People are now calling Alzhiemer's "diabetes of the brain": []

      Practises that drain sugar from the blood could help. Like, say, the 100-pushup (or more) challenge -- where you randomly exercise at various points in your day -- say, walk into an unoccupied office meeting room, do 20 pushups, then walk out.

      • (Score: 1) by sonamchauhan on Saturday March 03 2018, @09:34AM

        by sonamchauhan (6546) on Saturday March 03 2018, @09:34AM (#646969)

        More info:

        [ Mostly sourced from "What Doctors Don't Tell You" magazine Dec 2017 issue, article "Total Recall" on page 28 []. The part about aluminium electrodes in water heaters is from elsewhere]

        • Aluminium is a potent neurotoxin.
        • To eliminate ingested aluminium, drink silica-loaded water (eg, 'Fiji' mineral water) in the morning, followed by vigorous, sweat-inducing exercise (or a sauna) half an hour later. This helps your body sweat out aluminium. Research evidence confirming this effect is here [] and here []. Interesting, silica is shown to have a biological affinity [] for aluminium.
        • Avoid aluminium cookware and bottles which leach out this metal that ends up in your body. Importantly, avoid water heaters that use aluminium sacrificial electrodes to protect against corrosion. Avoid hot water from unknown heaters. Instead, boil your own water in stainless steel cookware as much as you can.
        • Avoid aluminium in food products. Commercial prebaked goods likely contain aluminium (it's commonly used in baking powder). Commercial table salt commonly has aluminium too. Instead, use aluminium-free salt (eg, aluminum free unrefined sea salt) and aluminium-free baking powder (eg, Bob's Red Mill aluminum free baking powder) to avoid this neurotoxin.
        • Don't use antiperspirants that contain aluminium salts. Better to stink than to die.
        • Coconut oil provides an alternate brain fuel that helps mitigate Alzheimer's decline. See this testimonial from Dr. Mary Newport [], who lost her husband, Steve, to this disease.
        • Curcumins (active ingredient compounds in turmeric) inhibit Alzheimer's disease plaques. A tiny amount of black pepper (just a punch) acts as a catalyst that skyrockets the body's absorption of curcumins.
        • Take this "nasty-but-effective" morning cocktail (from the article):

          • One heaping teaspoon of extra virgin coconut oil.
          • One heaping teaspoon of ground turmeric
          Combine these in a cup and stir to a paste. Add boiling water from the kettle to dissolve. John adds milk to cool the drink, then grinds on some fresh black pepper and puts it down the hatch.

          Suggestion: Made with coconut milk and a dash of cinnamon and ground ginger, or with a half teaspoon of cacao and honey, this might be more anti-inflammatory and palatable.

          Don't forget: drink 1.5 litres (about 50 fl oz) of high-silica mineral water such as Fiji or Volvic and exercise or sit in a sauna until you sweat.

    • (Score: 2) by realDonaldTrump on Saturday February 17 2018, @03:00AM

      by realDonaldTrump (6614) on Saturday February 17 2018, @03:00AM (#639178) Homepage Journal

      You're welcome! Now give a big Thank You to the folks in Congress -- on BOTH SIDES -- who are working very hard to take the shackles off our tremendous Pharmaceutical industry. Let me tell you, I went to a museum in Atlanta. And saw the shackles we put on the little slave children. We're doing the same thing to our Pharmaceutical industry. This BIPARTISAN bill will go a long way toward fixing that. I look forward to signing it. I'm in my office at Mar-a-Lago, my Southern White House, with pen in hand.

      My doctor says I'm in amazing health, he says I'm positive for everything. But some people aren't as lucky. I am going to take care of everybody. I don't care if it costs me votes or not.

  • (Score: 4, Insightful) by sjames on Saturday February 17 2018, @12:52AM (1 child)

    by sjames (2882) on Saturday February 17 2018, @12:52AM (#639143) Journal

    If at first you don't succeed, lower your standards.

    • (Score: 2) by black6host on Saturday February 17 2018, @01:04AM

      by black6host (3827) on Saturday February 17 2018, @01:04AM (#639148) Journal

      Indeed. I have enough qualifying things as it is, according to my ex-wife. Keep this up and she'll be my savior and I'll be behind bars :)

      My grandmother died from that kind of stuff and she was only 98. Poor soul. Gone long before her time. Yeah, she was a bitch and I'm a bastard :)