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barbara
01-27-2011, 02:19 PM
This article makes some good points about prevention of disease rather than trying to treat patients that are too far along to get benefit from the treatment. This would not include stem cell therapy however, which offers the possibility of regeneration.


By Jef Akst

While preclinical studies identify ways to prevent Alzheimer's disease in animals, human trials test these same therapies in symptomatic patients -- long after they are most likely to be effective

Published 26th January 2011

Alzheimer's disease (AD) is a growing threat that currently afflicts some 35 million people worldwide. Without the advent of preventive therapies, the neurodegenerative disease will strike as many as 100 million people by 2050. And while laboratory studies in animal models of AD continue to uncover promising avenues for disease prevention, clinical trials in humans target patients who are already showing signs of neural degeneration.


Image: Wikimedia commons, Alzheimer Forschung Initiative e.V.
Disease biologist Todd Golde of University of Florida College of Medicine talked to The Scientist about this disconnect, its consequences, and possible solutions to the problem -- the topic of an opinion piece he co-authored, published online today (January 26) in Neuron.

The Scientist: What are the current treatments for Alzheimer's disease?

Todd Golde: The two [classes of drugs] that have been approved are designed to enhance cognitive function. One is the cholinesterase inhibitors, and the other one is memantine. [Both yield] a transient increase in cognitive function, but it doesn't last. And there's no evidence that the course of the disease is changed or altered. It's really a fairly modest effect. So there's a real unmet medical need.

TS: What is the problem with how these treatments are being tested in humans?

TG: Over the last two decades, we've gained a fairly good understanding of certain steps that probably play an initiating role in Alzheimer's disease pathogenesis. I think the data is quite compelling that the accumulation of [amyloid-beta] peptides and aggregates drives this disease. But there's a misalignment between what we do in the laboratory, where we're largely doing a prevention study against that pathological feature, and in the clinic, where we're actually treating a symptomatic individual who has longstanding pathology and massive signs of neural degeneration. Why would removing the trigger of the disease at that point really have a major benefit?

TS: What are the possible consequences of this mistake?

TG: The biggest one is that it makes it much less likely that the therapies are going to show any signs of efficacy. Basically, they won't get approved. And if it costs $300-$600 million to conduct two pivotal phase III trials for an Alzheimer's disease drug, it's not going to be too long [before] people aren't going to invest. And now you want a prevention trial that's going to cost significantly more and is also going to take longer...so long that the patent is essentially expired by the time the drug gets approved.

Let's say you do have a disease modifying drug that slows the course of cognitive decline, but only does so in patients who have fairly advanced Alzheimer's disease. Does an individual really want that if it doesn't improve their function -- if it just slows the course and they're pretty far gone? That's a tough ethical question. If [a drug] is only partially effective, are you just prolonging suffering rather than actually improving it?

TS: What are some things that need to be addressed to solve this problem?

TG: First and foremost, when we consider prevention, a drug or a therapy has to be "safe enough." And when you're talking about treating people who are asymptomatic or "well," that bar is pretty high. I think that's the first issue from the medical and scientific side.

The second one is if you want to embark on realistic trials where you could actually execute them in a reasonable amount of time, it will be accepting biomarkers as surrogate endpoints for the disease. And that is not without risks. At this point I think we've make incredible progress [identifying biomarkers for] Alzheimer's disease pathology, but we don't have enough longitudinal data to say how long it will take any individual to progress on to additional neurodegeneration and cognitive impairment.

Then linked tightly to [these medical or scientific issues] are the financial obstacles of running prevention trials. I'm a scientist, I'm not a politician, I'm not a policy maker, I'm not a drug manufacturer. But I think these kinds of issues need to be spoken about in those types of settings if we really want to move toward a country that is serious about preventing illness.

TS: Do you think this prevention-treatment dilemma exists in drug research for other diseases? Is this a common misalignment between preclinical studies and human trials?

TG: For degenerative processes, I think for sure. We largely use genetics to help us identify the root cause, we find some therapies to target that, usually most effective in our animals models in a preventive setting. Then the trials are always done on people [with] pretty advanced disease, and they again fail to translate.

When we think about this idea of personalized genomic prediction of disease, if we do this testing and we want to realize the promise of it, then we have to think about therapies in the setting of prevention, not in terms of treatment.

T.E. Golde, et al, "Anti-Ab therapeutics in Alzheimer's disease: the need for a paradigm shift," Neuron, 69:203-13, 2011.


Q&A: Alzheimer's trial disconnect - The Scientist - Magazine of the Life Sciences

Jeannine
01-27-2011, 02:30 PM
My Dad died at age 81 last July from Alzheimer's and I don't think the drugs he was given made one bit of difference. I still don't understand why so much time and money needs to be spent to get a drug to makrket for people who are pretty much destined to die in a short while.

Get the drug out there and see if it works.

I know my family is predisposed to Alzheimer's due to my great grandmother and my Dad and his brother all having it. I read that Alzheimer is inherited through your mother. If I can find the article I will post it here.

Kaye
02-14-2011, 11:02 AM
They are talking "CURE" with only 20 treatments. It actually restored memory in mice. The drug, Leukine (GM-CSF) is already on the market for cancer. It is used to help cancer patients after chemo and has small, or no side effects. This would truly be a blessing.

Video on Alzheimer's Disease.

http://www.baynews9.com/video?clip=http://static.baynews9.com/newsvideo/bn9/arc/Alzheimers_In_Depth_0914.flv


Rheumatoid Arthritis Signaling Protein Reverses Alzheimer's Disease in Mouse Model
ScienceDaily (Aug. 23, 2010) ? A signaling protein released during rheumatoid arthritis dramatically reduced Alzheimer's disease pathology and reversed the memory impairment of mice bred to develop symptoms of the neurodegenerative disease, a new study by the University of South Florida reports. Researchers found that the protein, GM-CSF, likely stimulates the body's natural scavenger cells to attack and remove Alzheimer's amyloid deposits in the brain.


People with rheumatoid arthritis, a chronic disease leading to inflammation of joints and surrounding tissue, are less likely than those without arthritis to develop Alzheimer's. While it was commonly assumed that non-steroidal anti-inflammatory drugs may help prevent onset and progression of Alzheimer's disease, recent NSAID clinical trials proved unsuccessful for patients with Alzheimer's.

The USF researchers are among the first to look at what effect innate immunity gone awry in rheumatoid arthritis may play in protecting against Alzheimer's disease.

"Our findings provide a compelling explanation for why rheumatoid arthritis is a negative risk factor for Alzheimer's disease," said principal investigator Huntington Potter, PhD, professor of molecular medicine at the USF Health Byrd Alzheimer's Institute and director of the Florida Alzheimer's Disease Research Center.

"Moreover, the recombinant human form of GM-CSF (Leukine?) is already approved by the FDA and has been used for years to treat certain cancer patients who need to generate more immune cells," Dr. Potter said. "Our study, along with the drug's track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer's disease."

The researchers analyzed three rheumatoid arthritis growth factors in mouse models and identified the signaling protein GM-CSF as the most promising for potential protective benefit against Alzheimer's disease. Then, they peripherally injected GM-CSF into two groups of mice -- those genetically altered to develop memory problems mimicking Alzheimer's disease and normal, aged mice. Behavioral tests confirmed the Alzheimer's mice were exhibiting signs of memory impairment at age 12 months. Another two control groups of mice -- the Alzheimer's mice and normal mice -- were administered saline (placebo).

After the 10th day of injections, all the mice began a series of behavioral testing. At the end of the 20-day study, the cognitively impaired mice treated with GM-CSF performed substantially better on tests measuring their working memory and learning. In fact, their memories were similar to normal aged mice without dementia. Even the normal mice treated with GM-CSF performed slightly better than their untreated peers. The Alzheimer's mice administered saline continued to do poorly on the tests.

"We were pretty amazed that the treatment completely reversed cognitive impairment in 20 days," said Tim Boyd, PhD, who, together with Steven Bennett, PhD, is a study lead author.

In addition, the brains of GM-CSF-treated Alzheimer's mice showed more than a 50-percent decrease in beta amyloid, a substance forming the sticky clumps of plaques that are a hallmark of Alzheimer's disease. This reduction in Alzheimer's plaques and associated restoration of memory was accompanied by more immune cells known as microglia in the brain. Microglia are like the body's natural garbage collection cells that rush to damaged or inflamed areas to get rid of toxic substances.

The researchers suggest that GM-CSF boosted during the immune system overdrive of rheumatoid arthritis helps harness the beneficial properties of inflammation in the brain. The protein may do this by recruiting more microglia from the peripheral blood into the brain to remove Alzheimer's plaques, Dr. Potter said. An apparent increase in neural cell connections in the brains of the GM-CSF-treated mice may also help explain GM-CSF's association with improving memory decline in Alzheimer's disease, the researchers said.

The USF Health Byrd Alzheimer's Institute plans to begin a pilot clinical trial later this year investigating GM-CSF (Leukine) in patients with mild or moderate Alzheimer's disease.

Jeannine
02-14-2011, 11:59 AM
Kaye

It's criminal that the drug isn't being tried right now. I bet if one of these researchers has a loved one withAlzheimer's they would treat them. Naturally it come out 6 weeks after my Dad died last summer.

My family could be tested to see if we inherited the gene, but do I really need to know this right now when there is nothing to be done anyway?

When I read that the gene is carried through the female, I figured we might have gotten a pass.

Kaye
02-14-2011, 12:22 PM
My mother has Alzheimer's and I too am worried that they don't move quickly enough. The FDA drags their feet when they should have wings on their feet. This would help so many people now confined to nursing homes. Life could be so different for their "golden" years. The discovery was actually in 2007 if I heard the news reporter correctly. What is the hold up? Check out the number of grants to this doctor from the NIH and look at the date on them. What does that tell us? What goes on is criminal. Until it makes a difference to Congress, don't expect any changes. How do we make them realize that a lot of this research is a waste of time, money and most of all LIVES.

http://projectreporter.nih.gov/reporter_searchresults.cfm?&new=1&icde=6969141&loc=2&CFID=32668704&CFTOKEN=94968023

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Project Number Sub # Project Title Contact
Principal Investigator Organization FY Admin IC Funding IC FY Total Cost
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3P50AG025711-05S1

FLORIDA ALZHEIMER'S DISEASE RESEARCH
POTTER, HUNTINGTON
UNIVERSITY OF SOUTH FLORIDA
2010
NIA
NIA
$875,000



5P50AG025711-05

FLORIDA ALZHEIMER'S DISEASE RESEARCH
POTTER, HUNTINGTON
UNIVERSITY OF SOUTH FLORIDA
2009
NIA
NIA
$1,502,923



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Jeannine
02-14-2011, 02:39 PM
They should all be brought up on criminal charges for allowing people to die needlessly.

Does anyone know of a member of Congress who has a relative with Alzheimer's who might listen to us? I will gladly write to them and even start a petition if I know someone in DC might give a damn.

Kaye
03-05-2011, 01:58 PM
Jeannine,
I ran across this info today. It provides us with a starting place to contact someone outside the medical community that is interested in actually helping Alzheimers patients. Check out what DOCTOR Zaven Khachaturian, a FORMER DIRECTOR of Alzheimer’s research for the National Institutes of Health said about delaying the onset for five years. I would hate to be his patient.

http://www.nytimes.com/2010/12/16/us/politics/16alzheimer.html

[B]With Alzheimer’s Patients Growing in Number, Congress Endorses a National Plan
By PAM BELLUCK
Published: December 15, 2010

Congress has voted unanimously to create, for the first time, a national plan to combat Alzheimer’s disease with the same intensity as the attacks on AIDS and cancer.


The bill, expected to be signed by President Obama, would establish a National Alzheimer’s Project within the Department of Health and Human Services, to coordinate the country’s approach to research, treatment and caregiving.

Its goal, the legislation says, is to “accelerate the development of treatments that would prevent, halt or reverse the course of Alzheimer’s” and “improve the early diagnosis of Alzheimer’s disease and coordination of the care and treatment of citizens with Alzheimer’s.”

The project would include an advisory council of representatives from agencies like the Centers for Disease Control and Prevention, the National Institutes of Health, the Department of Veterans Affairs, the Food and Drug Administration, the Indian Health Service and the Centers for Medicare and Medicaid Services. Scientific experts, health care providers and people caring for relatives with Alzheimer’s would also be included.

If you go to war, you have planning, planning, planning,” said Representative Christopher H. Smith, Republican of New Jersey, who co-sponsored the bill. “Well, this is a war on a dreaded disease. We need to bring all the disparate elements together for the greatest possible result.” While the act itself does not authorize more money, one of the recommendations of the national plan “is likely to be for an increase in research money for Alzheimer’s,” said another co-sponsor of the bill, Senator Susan Collins, Republican of Maine.

“We spend one penny on research for every dollar the federal government spends on care for patients with Alzheimer’s,” she said. “That just doesn’t make sense. We really need to step up the investment.”

The legislation was driven by the rapidly rising number of people with Alzheimer’s — about 5.3 million now, and expected to triple by 2050. The cost of their care to Medicare and Medicaid was about $170 billion last year. By 2050, Ms. Collins said, it will grow to $800 billion a year, more than the military budget.

The House passed the bill on Wednesday, and the Senate last Thursday.

The advisory council would draft an annual report on federally financed programs involving research, treatment, nursing homes and home care, recommending which to expand or eliminate. It would also ensure that members of ethnic and racial groups at higher risk for Alzheimer’s be included in research and treatment.

Alzheimer’s experts said the effort could make a significant difference.

“What really makes this so powerful is that it takes us from a lot of small efforts going on locally to doing something in a coordinated way,” said Dr. Kenneth Kosik, a neuroscientist at the University of California, Santa Barbara. “If there’s one thing we know in science it is that to draw conclusions we need numbers, large-size populations to study.”

The national plan will reinforce efforts to detect brain changes that occur years before people develop symptoms of dementia, and to develop drugs to prevent or substantially delay symptoms.

“Dealing with symptoms only after the fact is not going to solve the problem,” said Dr. Zaven Khachaturian, a former director of Alzheimer’s research for the National Institutes of Health. Delaying symptoms for just five years, he said, “we will cut down tremendously” on the number of people who live long enough to develop Alzheimer’s.

Representative Edward J. Markey, a Massachusetts Democrat who co-sponsored the bill, said his mother had had Alzheimer’s. “We’re trying to create a sense of urgency so that we’re developing multiple pathways that ultimately might be successful,” he said. “We’ve done it with polio, we’ve done it with AIDS.

“It’s a unique disease to the extent that patients can’t lobby for themselves, and the person close to them cannot lobby because they’re home taking care of that person. There are no Alzheimer’s survivors.”