Alzheimer's treatment within reach

[humble3d]

Alzheimer's treatment within reach

 

Tablet that ‘switches off’ production of toxic amyloid proteins could be first treatment licensed in a decade if it is also shown to slow mental decline

The drug could be the first treatment for Alzheimer’s to be licensed in more than a decade.

 

An Alzheimer’s drug has been shown to successfully target the most visible sign of the disease in the brain, raising hopes that an effective treatment could be finally within reach.

 

A small trial of the drug was primarily aimed at assessing safety, but the findings suggest it effectively “switched off” the production of toxic amyloid proteins that lead to the sticky plaques seen in the brains of Alzheimer’s patients.

If the tablet, produced by pharmaceutical giant Merck, is also shown to slow the pace of mental decline – a crucial question that a major clinical trial should answer when it reports next year – it could be the first treatment for Alzheimer’s to be licensed in more than a decade.

Prof John Hardy, a neuroscientist at UCL who first proposed that amyloid proteins play a central role in Alzheimer’s disease, welcomed the results. “People are excited,” he said. “This is a very nice drug and I’m sure Merck are feeling very pleased with themselves.”

Matt Kennedy, who led the trial at Merck, said: “Today there are very limited therapeutic options available for people with Alzheimer’s disease, and those that exist provide only short-term improvement to the cognitive and functional symptoms.

They do not directly target the underlying disease processes. There is an urgent need for [these].”

The new therapy is designed to do this by halting the steady production of amyloid-beta proteins, which are known to clump together in sticky plaques in the brains of Alzheimer’s patients.

A leading theory of Alzheimer’s is that the accumulating proteins kill off healthy neurons, eventually leading to memory loss, cognitive decline and changes to personality.

Kennedy said it was too early to predict when a drug might reach the market if the next step is successful.

“We are eagerly awaiting the results of the phase three clinical trials,” he said. “It is premature to speculate on availability.”

In the trial, published in the journal Science Translational Medicine on Wednesday, 32 patients with early stage Alzheimer’s disease were given the drug, called verubecestat, daily for seven days.

Healthy volunteers were also given the drug for up to two weeks.

This was not long enough to show visible changes to the accumulation of plaques in the brain, by MRI scans for instance.

However, samples taken from the fluid surrounding the brain showed the drug had reduced the levels of two compounds that are known to be the building blocks for abnormal amyloid proteins.

Hardy said that the changes to the biomarkers convince him that the drug is successfully targeting the buildup of plaques in the brain.

The real remaining uncertainty, he said, was whether this would convert into cognitive benefits for patients.

“What we have to be worried about is that the plaques have set off other pathologies - that it is too late,” he said.

The drug works by blocking a brain enzyme called BACE1, which fuels the production of two small molecules that link together to form amyloids.

 

Mutations in genes related to BACE1 have been found in people who appear to be protected against Alzheimer’s disease.

There have been previous attempts to develop drugs that inhibit BACE1, but these have mostly failed due to unacceptable side-effects, such as liver toxicity and eye problems.

The Merck drug appears to have very few side-effects and it will be the first of its kind to make it into a large efficacy trial.

The company is running two phase three trials, in more than 2,000 patients with mild to moderate Alzheimer’s and in another 1,500 patients in the earliest stage of the disease.

The results of the first of these are due to be reported in July 2017.

There are 850,000 people with dementia in Britain, and this figure is expected to reach one million by 2025. Alzheimer’s is the most common form of the condition.

Rosa Sancho, head of research at Alzheimer’s Research UK, welcomed the findings, adding that the Merck drug is one of several that are heading into the final stages of clinical testing.

“There is a wave of potential new treatments currently being tested for dementia, with the results of these studies hotly anticipated over the course of the coming months and years,” she said.

Competing drugs include one developed by the biotech firm Biogen, which reported promising results in August and which also targets the plaques.

The Biogen drug aims to sweep the proteins away once they appear rather than halting the production of proteins in the first place, however.

“With us, it’s a question of switching off the tap. With them it’s mopping up the water,” said Ian McConnell, a spokesman for Merck.

Hardy suggested that Merck’s drug is likely to be far cheaper and easier to produce than the Biogen therapy, which involves injecting patients with antibodies.

• This article was amended on 4 November 2016 to correct the numbers of patients in the two phase three trials.

 

https://www.theguardian.com/society/2016/nov/02/alzheimers-treatment-within-reach-after-successful-drug-trial-amyloid-plaques-bace1

 

[nIGHT]

I might need this drug.

I'm also taking my own made drug to combat short term and long term memory loss and so far it reduced the symptoms.

When I was a teenager, I couldn't count the times I couldn't remember my name, who I am, where I am and why I'm there.

I often found myself looking at my wallet and be surprised about my ID and how I look.

There a note that saying "You don't know your name and who you are then read me."

There I wrote that I am sick and one of the effects are short and long term memory loss.and write an additional note that may help us in case it happened again.

After taking my own made medication, the symptoms lessened but I still suffered from random memory loss that takes a while to remember things.

One of my additional note, "How to find cure if we often forget what we read and know?".  

[vitorio]

Great discovery that gives hope to Alzheimer's patients. Hope, sooner, they find a discovery to the final treatment of it.

[mona]

I had to deal with my father's Alzheimer's like condition in the past and I can assure everyone - it's one of these horrible diseases I fear and would like to avoid the most.

[lurch234]

40 minutes ago, mona said:

I had to deal with my father's Alzheimer's like condition in the past and I can assure everyone - it's one of these horrible diseases I fear and would like to avoid the most.

 

I understand. My dad had the disease. At the end he was just a shell. Dead inside. He couldn't even remember what Christmas was. The worst part was you couldn't mourn him because he

just kept going on. Already dead but still living...

[mona]

On 30.11.2016 at 2:48 AM, nIGHT said:

I might need this drug.

I'm also taking my own made drug to combat short term and long term memory loss and so far it reduced the symptoms.

When I was a teenager, I couldn't count the times I couldn't remember my name, who I am, where I am and why I'm there.

I often found myself looking at my wallet and be surprised about my ID and how I look.

There a note that saying "You don't know your name and who you are then read me."

There I wrote that I am sick and one of the effects are short and long term memory loss.and write an additional note that may help us in case it happened again.

After taking my own made medication, the symptoms lessened but I still suffered from random memory loss that takes a while to remember things.

One of my additional note, "How to find cure if we often forget what we read and know?".  

 

The only thing I can do @nIGHT is giving you a warm-hearted hug.  I feel for you, friend. 

BTW

What is that "own made" drug of yours ?

[46&2]

My step father has this disease too. He is progressively getting worse. He used to be "the guy" when it came to fixing and building things. This man built his own house and was a farmer, maintaining all his own farm equipment. Now he is lucky to get his shoes on the correct feet. It is not only the one afflicted but the immediate family that is affected by this disease. My mom is a saint and am glad she has a strong constitution. Lets hope this treatment is realized and affordable to those who could benefit.

[nIGHT]

22 hours ago, mona said:

 

The only thing I can do @nIGHT is giving you a warm-hearted hug.  I feel for you, friend. 

BTW

What is that "own made" drug of yours ?

Thanks @mona

I am sorry I cannot share it with you.

 

 

 

[mazigh]

Let's hope they can find sth helpful and being available soon, I have some family members who suffer from it and it's really sad, the person that once was smart become in 1 year another person!, asking you the same questions again and again or telling you his old stories again and again without being able to know he/she already told you before... 

[Fallon]

16 hours ago, mazigh said:

Let's hope they can find sth helpful and being available soon

We all want that, but its questionable, because the causes are partly systemic.

So it could be something like: do not board your plane anymore. It can help.

Severe air pollution exposures produce systemic, respiratory, myocardial, and brain inflammation and Alzheimer’s disease.

 

 

[mazigh]

On 12/5/2016 at 2:51 PM, Fallon said:

We all want that, but its questionable, because the causes are partly systemic.

So it could be something like: do not board your plane anymore. It can help.

Severe air pollution exposures produce systemic, respiratory, myocardial, and brain inflammation and Alzheimer’s disease.

 

 

I don't know if this is true or not but from my humble observation I think it is not related, I believe from my point of view and observation that this disease have strong relation with: 1- abnormal sleep  (like not sleeping early or interrupted sleep) , 2- Physical inactivity , 3- Some medications (some drugs used in lowering pain-feeling, sleep drugs..) ;4- low exposure to sunlight and probably some genetic factor

[Fallon]

On 12/9/2016 at 8:42 PM, mazigh said:

I don't know if this is true or not but from my humble observation I think it is not related,

You may well be wrong, because this week more indications surfaced in 'The Lancet' that Air Pollution is a likely factor. Although it is is hard to be definitive yet.

Living near major roads and the incidence of dementia (...)

(In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia)

The points you mention are important, because it concerns other factors that we can influence: sleep well, be active etc. Like working with enough daylight and sleeping in darkness.

[mclaren85]

On 12/1/2016 at 1:01 PM, mona said:

I had to deal with my father's Alzheimer's like condition in the past and I can assure everyone - it's one of these horrible diseases I fear and would like to avoid the most.

What is your father's disease? And how is he now?

[nIGHT]

Those whose mother or father, or relative, that have any of these like sickness: Alzheimer, dementia and, short/long term amnesia not caused by accident or event trauma that is either temporary or permanet, I have a question for you. .

 

1. During their (your father/mother/relative) healthy life (before the symptoms appear), did they consume a lot of any of these items: potato, spinach, broccoli, tomato, carrots, rice, products that are made from yeast like breads and wines, red meats like beef, organ meats like liver and kidney parts of animal like cow or pig that is either cook for a specialty dish or made into sausages or made into a meatloaf-like products? How much is a lot? You ate mashed potato today and drinking wine and tomorrow you are having bread, the next two days you drank wine again, and the next day after that you have pizza and in the evening spinach with wine. In any of these items they are consume more than thrice a week. This may happened almost every week and sometimes a couple of weeks not consuming any of the above items then the cycle continues again. That is a lot. Or, it may seems that most of these items are consumed once every other week. That is a lot too.

 

2. Did they become very thin, thin or their was a noticeable drops in weighs just before, during or after the diagnosis? Or did their face become raisins-like after diagnosis? Please elaborate description which of these state their in.

 

3. Did they experience muscle pain, his/her body aches as if a weigh is being pressed on it or a lot of needles were pinching on it or seems they become tender and prone to get hurt much more easily 5-10 years before the diagnosis? (This is the hardest to know since the patient won't remember. His/her partner must have noticed it.)

 

Please, go investigate if you have time.

 

Note: If they did consume a lot and is suffering from any of the illness mentioned above then stop giving them foods that I mentioned above. If you have a family member especially either a father, mother, a brother or a sister which suffers from the illness above then you too might be susceptible to this illness especially if you ate the same kind of foods/meals everyday. Let's call this a genetic factor. Most people will share such intolerance to certain chemicals, elements or minerals on certain quantity. I think this is the reason why some people are not sickened with this disease because they can tolerate much higher levels of these things or their diets just supplement the prevention or consumption of these excesses. The reason why it is so hard to detect and cure. They should include having trouble concentrating as one of early symptoms. 

 

I will not be surprise that these med sites (and specialized doctors) or on tv shows will later show these information I'm giving out here, that's what their good at for, copying and pretending they know better just like the other research I did  with the assistance of my doctor.. Lol. They are giving medications without knowing what there are for. Exactly the same content as of my first notes on that disease! They could have asked for a more recent one and give credits to my doctor but you know a-hole will stole recognition. Note the date I posted it here.

[mona]

On 5.01.2017 at 10:58 PM, mclaren85 said:

What is your father's disease? And how is he now?

 

It is the old story. My father passed away couple years ago.

He'd never been clearly diagnosed with full-blown Alzheimer's Disease (doctors claimed that could have been done only by performing autopsy).

However the symptoms were very alike and he was sent to be treated by specialized alzheimer's medical center anyway. 

                         

[mona]

6 hours ago, nIGHT said:

Spoiler

Those whose mother or father, or relative, that have any of these like sickness: Alzheimer, dementia and, short/long term amnesia not caused by accident or event trauma that is either temporary or permanet, I have a question for you. .

 

1. During their (your father/mother/relative) healthy life (before the symptoms appear), did they consume a lot of any of these items: potato, spinach, broccoli, products that are made from yeast like breads and wines, liver and kidney parts of animal like cow or pig that is either cook for a specialty dish or made into sausages or made into a meatloaf-like products? How much is a lot? You ate mashed potato today and drinking wine and tomorrow you are having bread, the next two days you drank wine again, and the next day after that you have pizza and in the evening spinach with wine. In any of these items they are consume more than twice a week. This may happened almost every week and sometimes a couple of weeks not consuming any of the above items then the cycle continues again. That is a lot. Or, it may seems that any of these items are consumed once every other week. That is a lot too.

 

 

2. Did they become very thin, thin or their was a noticeable drops in weighs just before, during or after the diagnosis? Or did their face become raisins-like after diagnosis? Please elaborate description which of these state their in.

 

3. Did they experience muscle pain, or seems they become tender and prone to get hurt easily 5 years before the diagnosis? (This is the hardest to know since the patient won't remember. His/her partner must have noticed it.)

 

Please, go investigate if you have time.

 

I can't help you much with those questions, since :

1. I stopped living with my parents (or even in the same town) in the age of 17.

2. As I already said in another post - my father passed away a few years back.

However one thing I can confirm - yes, indeed - my father had  become very thin couple years before his death. But he'd underwent a stroke and a heart attack some years before his dementia - alzheimer's like symptoms started showing-off, so I'm not sure about the real culprit.

 

[nIGHT]

Note: Information below specifically posted as a reply to mona's post about regarding her deceased father's dementia and not some information that may confuse  other people reading this post directly without reading her posts first!

 

Note 2: The information inside the Reference 1 and 2 spoilers contains information about how dementia happened that is caused by one big stroke or a series of strokes/silent strokes. This does not explain dementia or alzheimer that is caused only by CFS-like symptoms and other unknown cause.

 

If he'd gone an alzheimer's like symptom after a stroke or heart attack then there is a probability that he might had have a Ruptured Brain Aneurysms.

 

Ruptured cerebral aneurysms are the most common cause of a type of stroke known as subarachnoid hemorrhage (SAH). That caused your father's alzheimer's like symptom called Vascular dementia. Vascular dementia is the second most common form of dementia and is caused by reduced blood flow to the brain—usually from a stroke or series of strokes. While the strokes may be unnoticeably small, the damage can add up over time, leading to memory loss, confusion, and other signs of dementia.

 

Reference 1

Spoiler

What is vascular dementia?

Vascular dementia refers to a progressive decline in memory and cognitive functioning caused by a blockage or reduction in the blood flow to the brain. When the blood supply to the brain is interrupted, brain cells are deprived of vital oxygen and nutrients, causing damage to the cortex of the brain—the area associated with learning, memory, and language. Vascular dementia is the second most common type of dementia after Alzheimer's disease, accounting for up to 40 percent of dementia cases in older adults.

Depending on the person, and the severity of the stroke or strokes, vascular dementia may come on gradually or suddenly, and can range from mild to severe. Currently, there is no known cure for vascular dementia, but there are steps you can take to help prevent strokes, compensate for cognitive losses, and slow its development.

Multi-infarct dementia: The most common type of vascular dementia

Multi-infarct dementia (MID) is caused by a series of small strokes (sometimes called "mini-strokes" or "silent strokes") that often go unnoticed. These mini-strokes, also referred to as transient ischemic attacks (TIAs), result in only temporary, partial blockages of blood supply and brief impairments in consciousness or sight. Over time, however, as more areas of the brain become damaged, the symptoms of vascular dementia begin to appear. MID usually affects people between the ages of 60 to 75, and is more common in men than women.

 

What is mixed dementia?

Although it is rarely diagnosed during life, up to 45 percent of people with dementia are believed to have mixed dementia, where more than one type of dementia occurs simultaneously, usually vascular dementia and Alzheimer’s disease or Lewy Body dementia.

The combination of two types of dementia can have a greater impact on the brain than either by itself. Mixed dementia is often indicated by cardiovascular disease and dementia symptoms that get worse slowly over time.

Signs and symptoms of vascular dementia

Vascular dementia affects different people in different ways and the speed of the progression varies from person to person. Some symptoms may be similar to those of other types of dementia and usually reflect increasing difficulty to perform everyday activities like eating, dressing, or shopping.

Behavioral and physical symptoms can come on dramatically or very gradually, although it appears that a prolonged period of TIAs—the mini-strokes discussed above—leads to a gradual decline in memory, whereas a bigger stroke can produce profound symptoms immediately. Regardless of the rate of appearance, vascular dementia typically progresses in a stepwise fashion, where lapses in memory and reasoning abilities are followed by periods of stability, only to give way to further decline.

 

Reference 2

Spoiler

Vascular Dementia and Alzheimer's

The cardinal sign of dementia is a decline in a person's normal intellectual functions--most notably, a decline in memory. Problems with short-term memory typically show up first. There may be general forgetfulness, or a tendency to misplace household items. But over time, the memory lapses become more severe, and the dementia begins to take a debilitating toll on thinking, judgment, communication, and emotional stability.

In people 65 or older, the most common cause of these crippling symptoms is Alzheimer's disease. But they are not the only causes. Dementia can also be a symptom, sometimes temporary, of dozens of diseases and disorders. These include poisoning, viral infections, malfunctioning glands, benign brain tumors, and severe nutritional deficiencies. About 10 percent of the time, these causes of dementia can be completely halted and reversed.

Not so in Alzheimer's disease: In lieu of a major medical breakthrough, Alzheimer's dementia cannot be prevented or cured. The drugs current prescribed for Alzheimer's temporarily alleviate, but do not reverse, some of the symptoms. Estimates of the number of people with Alzheimer's are uncertain, but most experts agree that up to 4 million people in the United States, or about 10 percent of people over the age of 65, now suffer from the illness.

It is less clear how often dementia traces to vascular problems. According to various estimates reported in the scientific literature, vascular dementia may account for one-tenth to one-third of all cases of dementia. Further complicating the situation, about one-fifth of people with Alzheimer's disease may also be suffering from vascular dementia. This is known as "mixed" dementia.

One of the few clear distinctions between vascular dementia and Alzheimer's disease concerns the way in which the major symptoms take hold. Alzheimer's is insidiously gradual. Over time, the minor forgetfulness grows more severe and disruptive, and additional symptoms begin to show up, such as disorientation and confusion over ordinary tasks such as shopping and cooking meals.

These gradual changes reflect the slow accumulation of abnormal proteins in the brain. In contrast, the symptoms of vascular dementia can worsen noticeably from one day to the next. This reflects the death of large numbers of brain cells that have been deprived on their blood supply. If Alzheimer's disease is a shallow, downward slope, vascular dementia is a staircase.

Causes of Vascular Dementia

The underlying cause of vascular dementia is an interruption of blood flow to the brain. Starved of oxygen for even a short time, brain cells perish. To understand how vascular dementia progresses, it helps to picture the mind as a vast field of brain cells fed by a complexly branching irrigation system. The main lines enter the brain at the base of the skull and split into smaller arteries, which subdivide into even smaller capillaries.

Over a lifetime, things can go wrong with the brain's irrigation system. For one thing, a weak patch on an artery wall can balloon outward, forming an aneurysm. If the aneurysm bursts, brain cells "downstream" are deprived of oxygen and perish. The cerebral arteries may also develop blockages, or blood clots. A severe blockage may affect a large region of the brain, causing symptoms such as paralysis, loss of speech, and even death.

These symptoms are the hallmarks of a stroke: an interruption of blood flow in the cerebral arteries, causing the death of brain cells. "Stroke" is an umbrella term that applies to a wide range of blockages and bleeding-whether large or small, momentary or prolonged. Stroke specialists suspect that most cases of vascular dementia trace to a series of small, short-lived blockages that affect relatively small patches of brain cells. Over time, however, the cumulative effect of many small strokes can lead to a condition known as multi-infarct dementia. The severity of multi-infarct dementia depends both on the location of the blockages and the number of them.

 

Still even with the above information I post above, when you mentioned he suddenly had a weigh loss then that might be due to chemical imbalance being caused by organ malfunctioning due to stroke or simply caused by diet. Of course, this is my opinion and not a medical fact. You cannot see my comment here below (this paragraph where this sentence belongs) in any med sites, books or journals. My theory is that chemical imbalance was also causing his organs to fail and he might have a large possibility of showing a CFS-like symptoms many months, probably a year, before his final day. This is new. This might be the last case of CFS I haven't covered and named. Thank you very much for your help mona.  You helped me a lot more than you can imagined.

 

[mazigh]

On 1/5/2017 at 3:44 PM, Fallon said:

You may well be wrong, because this week more indications surfaced in 'The Lancet' that Air Pollution is a likely factor. Although it is is hard to be definitive yet.

Living near major roads and the incidence of dementia (...)

(In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia)

The points you mention are important, because it concerns other factors that we can influence: sleep well, be active etc. Like working with enough daylight and sleeping in darkness.

Maybe it is true and it is likely to happen, thanks for the info, I know 3 family members who suffer this and close to each other, the first is my Grandfather from mother side, one is an old women of the same family and the last the daughter of the old women (BTW they are all old now), the grandfather born in northern Morocco(Rural Area with no pollution I think), spent his childhood in a rural area Near Oran (French Algeria), then went to France for 2 years or so and then to Germany for so many years, the old woman born in northern Morocco, spent some years in the same area (near Oran too, they both were neighbors) and then spent the rest in a big city in Morocco, and for the her daughter she is born in the same rural area near Oran, spent her childhood there then she came with her mother to a big city in Morocco, Now what do you think? Is it genetic or has a relation with the Rural area of Oran?!