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frojack writes:

Neuroplasticity, the ability of the brain, during critical periods of development, to easily change its structure in response to environmental stimuli, declines by adulthood. In humans this happens by age 6. From then on it gets progressively harder to restructure the brain to handle the creation of new synapses.

The Scientist reports on a new study that suggests that this decline is actively caused through out later life by the creation of of a certain protein in the brain. And suppressing that protein allows the brain to regain its neural plasticity.

The brain doesn't actually lose its ability to adapt or make new neural connections, rather that ability is suppressed, activity turned off. The switch has been found to be a paired-immunoglobulin–like receptor B (PirB) protein produced by the brain itself.

The study describes curing Lazy Eye in mice, by covering the "Good Eye". Which is exactly what is done in children. Caught early enough, the brain and visual cortex will adapt to this change in stimuli by building up the fine neuron structures so that the lazy eye will be resume development, and often achieve normal vision.

With the mice, they induced lazy eye intentionally, by covering one eye long enough to cause the brain to "abandon" it.

Later in the mouse's life they introduced an inhibitor to the PirB Protein, removing the suppression of the brain's Neuroplasticity, and then covering the good eye. They saw new functional synapses form, demonstrating that even when PirB is inhibited in a short, one-week time frame, new neuron connections—and recovery from lazy eye—is possible in an adult mouse.

Now Lazy Eye isn't that big of a problem in children if caught early, and lazy eye in mice is even less of a concern, except to the mice.

Rather, the focus of the research is restoring Neuroplasticity to the brain, to handle brain injury or illness later in life. By "turning back the clock" of the brain's developmental cycle, the ability of the brain to adapt itself may be restored long enough to "route around the damage".

Their study has shown that that mice without PirB are partly resistant to memory loss in an Alzheimer’s model. This suggests that maybe the same drug for vision loss could also work for Alzheimer’s disease.

[Title change to correct typo - Ed.]

takyon writes:

Scientists have made progress on a cure for Alzheimer's:

Experts at Adelaide's Flinders University have made an Alzheimer's breakthrough that may result in world's first dementia vaccine. Developed by Australian and US scientists, this vaccine may not only prevent but also reverse early stages of Alzheimer's, the most common form of dementia.

The Alzheimer's vaccine may be tested on humans within the next two to three years after being bankrolled by the US Government. Scientists from Flinders University and America's Institute of Molecular Medicine and University of California developed the vaccine by targeting proteins in the brain that block neurons.

The formula targets tau proteins and abnormal beta-amyloid that cause Alzheimer's. The scientists are confident that the vaccine would eventually be used as preventative vaccine. According to Flinders University medicine professor Nikolai Petrovsky, the proteins must be removed from the brain as Alzheimer's, and dementia sufferers have lots of these broken down proteins inside.

Alzheimer's disease Advax^CpG- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules (open, DOI: 10.1038/srep28912)

Original Submission

hemocyanin writes:

I ran across a story in the acclaimed “medical journal”, International Business Times, about how an old PMS medication from the 60s might be an Alzheimer's cure. Considering the source, I don't put a ton of stock in the story but it was interesting enough to look around a little more. That led me first to wikipedia to learn a little more about the drug in question (sounds like it has nasty side effects), which is when I got totally sidetracked:

Mefenamic acid is generic and is available worldwide under many brand names.[5]

In the USA, wholesale price of a week's supply of generic mefenamic acid has been quoted as $426.90 in 2014. Brand-name Ponstel is $571.70.[15] In contrast, in the UK, a weeks supply is £1.66, or £8.17 for branded Ponstan.[16] In the Philippines, 10 tablets of 500 mg generic mefenamic acid cost PHP39.00 (or the equivalent of $0.88USD) as of October 25, 2014.

The numbers in wikipedia may be extreme, but not by much. Looking online, I see that thirty 250mg tablets cost at least $111 at Walmart. In an almost direct reversal of the quantity and price numbers, one hundred 250mg tablets cost $35 from a UK manufacturer, but to get the drug at that price, you must break Federal law.

The rest of my comment would be a long string of expletives which I shall omit.

Original Submission

MrPlow writes:

Submitted via IRC for cmn32480 with a story that appeared in ScienceAlert:

Australian researchers have come up with a non-invasive ultrasound technology that clears the brain of neurotoxic amyloid plaques - structures that are responsible for memory loss and a decline in cognitive function in Alzheimer's patients.

If a person has Alzheimer's disease, it's usually the result of a build-up of two types of lesions - amyloid plaques, and neurofibrillary tangles. Amyloid plaques sit between the neurons and end up as dense clusters of beta-amyloid molecules, a sticky type of protein that clumps together and forms plaques.

Neurofibrillary tangles are found inside the neurons of the brain, and they're caused by defective tau proteins that clump up into a thick, insoluble mass. This causes tiny filaments called microtubules to get all twisted, which disrupts the transportation of essential materials such as nutrients and organelles along them, just like when you twist up the vacuum cleaner tube.

[...] Publishing in Science Translational Medicine , the team describes the technique as using a particular type of ultrasound called a focused therapeutic ultrasound, which non-invasively beams sound waves into the brain tissue. By oscillating super-fast, these sound waves are able to gently open up the blood-brain barrier, which is a layer that protects the brain against bacteria, and stimulate the brain's microglial cells to activate. Microglila cells are basically waste-removal cells, so they're able to clear out the toxic beta-amyloid clumps that are responsible for the worst symptoms of Alzheimer's.

The team reports fully restoring the memory function of 75 percent of the mice they tested it on, with zero damage to the surrounding brain tissue. They found that the treated mice displayed improved performance in three memory tasks - a maze, a test to get them to recognise new objects, and one to get them to remember the places they should avoid.

[...] The team says they're planning on starting trials with higher animal models, such as sheep, and hope to get their human trials underway in 2017.

Original Submission

Phoenix666 writes:

"Age-related neurodegenerative diseases, like Alzheimer's, progress over a long period of time before they become clinically apparent. The earliest physiological and molecular events are largely unknown," said Mastroeni. "Findings from our laboratory have uncovered early expression changes in nuclear-encoded, but not mitochondrial-encoded mRNAs occurring in one's early 30s, giving us a glimpse into what we suspect are some of the earliest cellular changes in the progression of Alzheimer's disease."

Results of the new study show that specific classes of genes associated with mitochondrial cell respiration display reduced expression levels in patients with Alzheimer's disease, compared with normal patients.

The study also examines gene expression in subjects whose brains show an intermediate level of illness known as mild cognitive impairment. Here, the opposite effect is observed, with relevant genes exhibiting increased levels of expression. The authors suggest this observation may point to some kind of compensatory mechanism in the brain attempting to stave off the disease in its earlier stages.

Further, the study proposes that restoring a specific set of damaged genes linked to mitochondrial function and located in the nuclear DNA of cells may offer a promising strategy for halting the disease's advance.

Journal: Nuclear but not mitochondrial-encoded OXPHOS genes are altered in aging, mild cognitive impairment, and Alzheimer's disease. Alzheimer's and Dementia, 2016; DOI: 10.1016/j.jalz.2016.09.003

Simply put, the mitochondria run out of gas, and Alzheimer's follows.

Original Submission

An Anonymous Coward writes:

Dr. Derek Lowe, from In the Pipeline, writes about another disappointing failure to treat Alzheimer's Disease:

The good news about this study is that it adds to the evidence that the amyloid hypothesis of Alzheimer's Disease is a blind alley and that the presence of amyloid plaques is simply correlative and not causative. As more data comes in from the study, I hope that the evidence will be conclusive enough that more effort will be spent on pursuing other therapeutic targets.

See also: https://en.wikipedia.org/wiki/Alzheimer's_disease#Amyloid_hypothesis

Original Submission

An Anonymous Coward writes:

Dr. Lowe, from In the Pipeline, writes of how the efficacy requirements of the FDA save US taxpayers money:

Note: Bold added by submitter.

http://blogs.sciencemag.org/pipeline/archives/2017/05/09/there-are-failures-you-know
http://www.nejm.org/doi/full/10.1056/NEJMp1701047
https://en.wikipedia.org/wiki/Solanezumab
https://en.wikipedia.org/wiki/Alzheimer%27s_disease
https://soylentnews.org/article.pl?sid=16/11/27/0147228
https://soylentnews.org/article.pl?sid=17/02/16/0116248

Original Submission

takyon writes:

https://news.ubc.ca/2017/10/31/alzheimers-disease-might-be-a-whole-body-problem/

Alzheimer's disease, the leading cause of dementia, has long been assumed to originate in the brain but new research indicates that it could be triggered by breakdowns elsewhere in the body.

The findings, published today in Molecular Psychiatry [DOI: 10.1038/mp.2017.204] [DX], offer hope that future drug therapies might be able to stop or slow the disease without acting directly on the brain, which is a complex, sensitive and often hard-to-reach target. Instead, such drugs could target the kidney or liver, ridding the blood of a toxic protein [amyloid-β protein] before it ever reaches the brain.

"Alzheimer's disease is clearly a disease of the brain, but our research shows that we need to pay attention to the whole body to understand where it comes from, and how to stop it," said Dr. Weihong Song, UBC psychiatry professor.

Original Submission

takyon writes:

Microsoft founder Gates commits $100 million for fund, start-ups, to fight Alzheimer's

Billionaire Microsoft co-founder Bill Gates is to invest $50 million in the Dementia Discovery Fund, a venture capital fund that brings together industry and government to seek treatments for the brain-wasting disease. The investment is not part of Gates' philanthropic Bill & Melinda Gates Foundation and will be followed with another $50 million in a number of start-up ventures working in Alzheimer's research, Gates said.

With rapidly rising numbers of people suffering from Alzheimer's and other forms of dementia, the disease is taking a growing emotional and financial toll as people live longer, Gates told Reuters in an interview. "It's a huge problem, a growing problem, and the scale of the tragedy - even for the people who stay alive - is very high," he said.

Despite decades of scientific research, there is no treatment that can slow the progression of Alzheimer's. Current drugs can do no more than ease some of the symptoms. Gates said, however, that with focused and well-funded innovation, he's "optimistic" treatments can be found, even if they might be more than a decade away.

Original Submission

takyon writes:

Alzheimer's protein may spread like an infection, human brain scans suggest

For the first time, scientists have produced evidence in living humans that the protein tau, which mars the brain in Alzheimer's disease, spreads from neuron to neuron. Although such movement wasn't directly observed, the finding may illuminate how neurodegeneration occurs in the devastating illness, and it could provide new ideas for stemming the brain damage that robs so many of memory and cognition.

[...] Researchers at the University of Cambridge in the United Kingdom combined two brain imaging techniques, functional magnetic resonance imaging and positron emission tomography (PET) scanning, in 17 Alzheimer's patients to map both the buildup of tau and their brains' functional connectivity—that is, how spatially separated brain regions communicate with each other. Strikingly, they found the largest concentrations of the damaging tau protein in brain regions heavily wired to others, suggesting that tau may spread in a way analogous to influenza during an epidemic, when people with the most social contacts will be at greatest risk of catching the disease.

The research team says this pattern, described yesterday in Brain [open, DOI: 10.1093/brain/awx347] [DX], supports something known as the "transneuronal spread" hypothesis for Alzheimer's disease, which had previously been demonstrated in mice but not people. "We come down quite strongly in favor of the idea that tau is starting in one place and moving across neurons and synapses to other places," says clinical neurologist Thomas Cope, one of the study's authors. "That has never before been shown in humans. That's very exciting." Because the researchers looked at Alzheimer's patients with a range of disease severity, they were also able to demonstrate that, when tau accumulation was higher, brain regions were on the whole less connected. The strength of connections also decreased, and connections were increasingly random.

Original Submission

takyon writes:

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.

takyon writes:

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