As seen 2010-08-28 pm time at huffingtonpost.com.
Reprinted for scholar and public information only.
Alex Koudinov: Dear reader, please make a visit to the web site of original publication, so, this interesting article original web page gets proper recognition, thanks!
*****
The news about Alzheimer's is dismal. A new Eli Lilly drug to treat Alzheimer's has failed big-time. After investing hundreds of millions of dollars in the drug, Semagacestat, the company announced it made patients worse.
And the latest idea from an elite circle of Alzheimer's researchers is to torture us with diagnostic spinal taps and brain scans, so we can know ten years in advance if we are heading lickety split into Alzheimer's even though specialists admit they have no treatment to stop it and are even losing faith in their long-held theories of what causes it. "This is a time of major soul-searching in the field," lamented Duke University researcher, Dr. P. Murali Doraiswamy, in the New York Times.
As a person who carries the major gene, ApoE4 for Alzheimer's, I am intensely tuned into and disturbed by this public conversation. The gene triples my risk of ending up with Alzheimer's. Some 77 million other Americans also carry ApoE4 (25 percent of the population), but few know it, and doctors are reluctant to test and tell, supposedly because they don't want to scare us. I accidentally discovered my gene via a blood test for cholesterol factors several years ago, and I'm glad I did, because it energized me to search for answers other than those from Big Pharma and its philosophical collaborators.
I have discovered a large contingent of Alzheimer's researchers who are extremely positive about prevention and not counting on an elusive drug to stymie the growing Alzheimer's epidemic of aging baby boomers. Investigators Gregory Cole and Sally Frautschy at UCLA's Center for Alzheimer's Research and Gary W.Arendash, PhD, at the Florida Alzheimer's Research Center, for example, are all focusing on prevention. There is a plethora of upbeat dialogue in the scientific community that does not grab headlines because it's not about big money and a magic cure. It's primarily about what people can do to change their own trajectory toward Alzheimer's.
Contrast the recent disturbing headlines in the New York Times about Alzheimer's drugs and diagnosis with the June, 2010 issue of the Journal of Alzheimer's Disease. It is a special issue devoted to finding ways to prevent Alzheimer's. Editors in chief George Perry, University of Texas at San Antonio and Mark A. Smith, Case Western Reserve, (who predicted the failure of Lilly's drug and others like it,) and guest editor, Jack de la Torre at the Center for Alzheimer's Research, Banner Sun Health Research Institute in Arizona all endorse the science showing how this disease can be cut off at the pass earlier in life.
Dr. de la Torre boldly asserts that finding a cure for Alzheimer's is a delusionary quest unlikely to happen in a hundred years and most probably, never. He argues that even if you could replace dead neuronal networks, bringing a shrunken Alzheimer's brain back to life, the persona and intellect of the individual would be so altered as to create a different personality. "Alzheimer's is incurable, but it is preventable," he says. "We need to identify and lower Alzheimer's risk factors in people when they are still cognitively normal and long before irreversible symptoms appear."
While the search for a pharmaceutical cure plays front and center, quietly in the background countless neuroscientists worldwide have concluded that Alzheimer's, as well as memory decline and other age-related dementias are actually slow-developing chronic diseases, like heart disease and cancer, partly dependent on lifestyle and other treatable diseases.
De la Torre, for example, is convinced that Alzheimer's and dementia are particularly tied to cardiovascular factors, notably, constricted blood flow to brain cells, and that midlife screening to detect and correct such heart-related deficits would help prevent much brain degeneration during aging. The special journal issue produced by de la Torre, called "Basics of Alzheimer's Disease Prevention," also included new research on the relationship between Alzheimer's and diabetes, high blood pressure, triglycerides, cholesterol and cholesterol- lowering drugs, (statins), a Mediterranean diet, exercise, fish oil, B vitamins and antioxidants.
This special issue of JAD is but the latest example of a shifting paradigm toward prevention. Other leading medical journals are full of studies, often funded by your tax dollars, filtered through the National Institutes of Health, revealing the dangers of alcohol, smoking, toxic chemicals, head injuries, infections, certain forms of anesthesia, excess copper, low vitamin B, excess calories, obesity, diabetes, thyroid problems, sleep deprivation, and depression in raising your risk of dementia and Alzheimer's.
The wisdom of Alzheimer's prevention, derived from the famous Nun Study at the University of Minnesota, and the Religious Orders Study, at Rush University in Chicago, has been piling up for a decade or two, but is rarely put into practice. Comparing brains at autopsy with lifestyle and cognitive status allows investigators to proclaim the value of mental, social and physical stimulation in building a brain more resistant to Alzheimer's. Best time to start: when you are young, but even activity in old age can make a huge difference.
Prolific research from the U.S. Department of Agriculture, UCLA, Tufts University and Columbia University College of Physicians and Surgeons, as well as dozens of other institutions, reveals a reduced Alzheimer's risk from consuming berries, nuts, curry powder, fruits and vegetables, fatty fish, olive oil and the Mediterranean diet, and various supplements, including folic acid, alpha lipoic acid, Vitamin B12, multivitamins and vitamin D.
We are missing the boat when we allow a small fragment of the scientific conversation about Alzheimer's, centered on ineffective pharmaceuticals and frightening diagnostic methods, drown out the momentous message coming from another research perspective: that we can take action right now to delay the progression and onset of Alzheimer's which happens over decades. The good news is that we know now how to detect and lessen many midlife lifestyle problems that may otherwise lead to irreversible dementia. The approach is much the same, Dr. De la Torre points out, as we now use extensively to prevent heart disease, cancer, diabetes and other chronic diseases of aging.
Obviously, this doesn't mean we should stop searching for treatments for the underlying causes and symptoms of Alzheimer's and other dementias or spare funding to relieve those already suffering.
But it is urgent that we have a vigorous dialogue about how to rescue the multitudes now racing at breakneck speed toward Alzheimer's. Unless we intervene, Alzheimer's cases in the United States will nearly triple. A May Alzheimer's Association report, "Changing the Trajectory of Alzheimer's Disease," predicts that cases will jump from 5.1 million to 13.5 million by 2050 with costs during that period exceeding $20 trillion in today's dollars.
If we could delay the onset of Alzheimer's by only five years, according to the report, some 1.6 million Americans expected to get Alzheimer's by 2015 and nearly 6 million scheduled to get it by 2050 would remain free of it while Medicare savings would be $33 billion in 2020 and $283 billion by mid century.
The only way to make that happen is to start talking as loudly about preventing Alzheimer's -- and listening to the researchers who can tell us how to do that -- as we do about trying to cure it.
Jean Carper is the author of 100 Simple Things You Can Do to Prevent Alzheimer's and Age-Related Memory Loss (Little, Brown & Company, September 2010).
Showing posts with label Alzheimer's disease research. Show all posts
Showing posts with label Alzheimer's disease research. Show all posts
2010/08/20
Stress in mid-life increases chances of dementia, research by Swedish scientists says
Excerpt: As per a new study conducted by Swedish scientists, the mid-life stress in women can give way to Alzheimer's disease in them.
The research concluded that women with frequent and high-level of stress and anxiety during their middle ages are more threatened to get affected by dementia, as compared to those who don’t.
The results were published in the journal Brain...
Continue reading original publication
The research concluded that women with frequent and high-level of stress and anxiety during their middle ages are more threatened to get affected by dementia, as compared to those who don’t.
The results were published in the journal Brain...
Continue reading original publication
2010/08/19
Drug's Failure invalidates the Tactic in Alzheimer's Battle, New York Times article correctly implies, says Alexei Koudinov of AlzClub.org
Drug's Failure Casts Doubt on a Tactic in Alzheimer's Battle - Gina Kolata, NYTimes, commented by A Koudinov, an excerpt(summary) and full comment are available
Reprinted for educational Alzheimer's scholar information purpose only, originally seen at New York Times Online
Drug’s Failure Casts Doubt on a Tactic in Alzheimer’s Battle
Alexei Koudinov note: it was never promising, who told you that? Did you check their scientific and ethical credit history first? You should! I checked and never believed those bastards of Alzheimer's leadership, "Professors" on campuses of major Universities and Medical centers. Want a referenced proof? Here it is, United Kingdom Parliament Written Evidence for the Science and technology Committee, check it out. I would infact ban them from doing science in early 2000, I asked Office of Research Integrity and SEC to do it. No reply yet]
By Gina Kolata Published: August 18, 2010
The failure of a promising Alzheimer’s drug in clinical trials highlights the gap between diagnosis — where real progress has recently been made — and treatment of the disease.
It was not just that the drug, made by Eli Lilly, did not work — maybe that could be explained by saying the patients’ illness was too far advanced when they received it. It was that the drug actually made them worse, the company said. And the larger the dose they took, the worse were patients’ symptoms of memory loss and inability to care for themselves. Not only that, the drug also increased the risk of skin cancer.
So when Lilly announced on Tuesday that it was ending its large clinical trials of that drug, semagacestat, researchers were dismayed.
“Obviously, this is disappointing news, to say the least,” said Dr. Steven Paul, an Alzheimer’s researcher and a recently retired executive vice president at Lilly.
Beyond the setback for Lilly, the study raises questions about a leading hypothesis of the cause of Alzheimer’s and how to treat it. The idea, known as the amyloid hypothesis, says the disease occurs when a toxic protein, beta amyloid, accumulates in the brain. The idea is that if beta amyloid levels are reduced, the disease might be slowed, halted or even prevented if treatment starts early enough.
The Lilly drug, like most of the more than 100 Alzheimer’s drugs under development, blocks an enzyme, gamma secretase, needed to make beta amyloid. It was among the first shown to broach the blood-brain barrier and reduce levels of beta amyloid in the brain. And, company studies showed, it did reduce amyloid production.
“We did get enough in the brain to have an effect,” said Dr. Eric Siemers, medical director of Lilly’s Alzheimer’s disease team. “Unfortunately, the effect was not what we wanted.”
Now researchers are focused on what went wrong, and why.
Some, like Dr. Lon Schneider, an Alzheimer’s researcher at the University of Southern California, say the drug’s failure may mean the field is rushing off a cliff in its near single-minded focus on blocking the production of amyloid. Dr. Schneider, like most leading Alzheimer’s researchers, consults for a number of drug companies, including Lilly.
The Lilly study’s failure, he said, “chips away at that approach to testing the amyloid hypothesis.”
“We don’t know what the drug targets for Alzheimer’s disease are,” Dr. Schneider said. “We don’t know because we don’t know the causes of Alzheimer’s.”
At the very least, said Dr. P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University, the Lilly result “clearly tells us that our current views may be too simplistic.”
Dr. Doraiswamy said he was not abandoning the amyloid hypothesis. But, he said, “this is a time of major soul searching in the field.”
“What worries me is that we don’t know if this was a toxicity unique to Lilly’s drug and this late-stage population or whether it also applies to similar anti-amyloid therapies given at earlier stages of the disease,” Dr. Doraiswamy said.
The bad news came on the heels of what researchers see as a resurgence of hope in this challenging field. With new cooperation in research they have made advances in diagnosing Alzheimer’s, a disease that used to be uncertain until autopsy.
And those new diagnostic tests are still exciting, researchers said.
PET scans of amyloid plaques in the brain and tests of cerebrospinal fluid can show amyloid accumulation long before people have symptoms of Alzheimer’s disease and, as was recently reported, appear to identify people at high risk of developing the disease. Researchers believe the best time to try to alter the course of the disease is before memory loss — by that time, brain cells are dead or dying and are unlikely to be restored.
At this point, though, when there is no treatment, those tests are primarily a benefit for companies testing new therapies and researchers trying to understand the disease’s progress.
The long journey of semagacestat began more than a decade ago, when Lilly scientists discovered it could block gamma secretase in laboratory experiments. Years of work followed, showing it appeared safe, that it got into the brains of people, that it reduced the production of amyloid in the brain.
Finally, in 2008, Lilly began two large studies of semagacestat, enrolling more than 2,600 people with Alzheimer’s disease. The company did not expect its drug to reverse the disease — patients’ brains were too ravaged for that, said Richard Mohs, Lilly’s team leader in Alzheimer’s research. But it did hope to slow the disease’s progression.
Now, with the abrupt end of the studies, patients will continue to be followed but no one will be taking any more of the drug.
“The fact that people got worse means there is biology we don’t understand,” Dr. Mohs said.
There are several possible explanations.
page 2
One is that the drug altered the functioning of other proteins in the brain and body — it now appears that gamma secretase is involved in the production of about 20 proteins in addition to beta amyloid. Companies, including Lilly, are developing drugs that block gamma secretase from making amyloid but do not have much of an effect on the other proteins.
One company, Bristol-Myers Squibb, says that is what its drug does. Its drug is now being tested in two clinical trials. In one, the participants have Alzheimer’s. In the other, they have memory impairment that falls short of Alzheimer’s dementia and have brain amyloid PET scans and tests of cerebrospinal fluid showing amyloid is accumulating in their brains, indicating that they are likely to go on to develop Alzheimer’s.
“We still like the amyloid hypothesis,” said Charlie Albright, a Bristol-Myers group director in neuroscience biology. The Lilly drug failure “doesn’t affect our enthusiasm about going forward.”
Another possibility is that the enzyme is decreasing production not just of a dangerous form of amyloid, known as a beta 42, but also of another form, a beta 40, that may protect the brain. Companies are developing so-called selective gamma secretase inhibitors, Dr. Paul said, which only block the production of a beta 42.
Companies are also pursuing other ways of reducing amyloid levels in the brain. One, a Lilly drug that uses a monoclonal antibody to block amyloid, is being tested in a large clinical trial.
And companies are pursuing a more difficult target — blocking a protein, tau, that accumulates in dead and dying nerve cells after the disease is under way.
But Alzheimer’s experts worry about the future. The research is extremely expensive — Lilly spent hundreds of millions of dollars on its failed drug — and it can take a decade or more to know if a drug works. It can take even longer if drugs are tested in people with mild symptoms of Alzheimer’s disease or in people who are at high risk but have no symptoms yet — a direction many think is necessary to really make a difference.
“I am certainly concerned that if we see some more failures it will be a harder to convince companies to invest that much money in testing these hypotheses,” Dr. Paul said.
Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai Medical Center, shares that concern.
“Failures certainly don’t build energy and enthusiasm,” he said. “The market is still there, but failures do take their toll.”
Reprinted for educational Alzheimer's scholar information purpose only, originally seen at New York Times Online
Drug’s Failure Casts Doubt on a Tactic in Alzheimer’s Battle
Alexei Koudinov note: it was never promising, who told you that? Did you check their scientific and ethical credit history first? You should! I checked and never believed those bastards of Alzheimer's leadership, "Professors" on campuses of major Universities and Medical centers. Want a referenced proof? Here it is, United Kingdom Parliament Written Evidence for the Science and technology Committee, check it out. I would infact ban them from doing science in early 2000, I asked Office of Research Integrity and SEC to do it. No reply yet]
By Gina Kolata Published: August 18, 2010
The failure of a promising Alzheimer’s drug in clinical trials highlights the gap between diagnosis — where real progress has recently been made — and treatment of the disease.
It was not just that the drug, made by Eli Lilly, did not work — maybe that could be explained by saying the patients’ illness was too far advanced when they received it. It was that the drug actually made them worse, the company said. And the larger the dose they took, the worse were patients’ symptoms of memory loss and inability to care for themselves. Not only that, the drug also increased the risk of skin cancer.
So when Lilly announced on Tuesday that it was ending its large clinical trials of that drug, semagacestat, researchers were dismayed.
“Obviously, this is disappointing news, to say the least,” said Dr. Steven Paul, an Alzheimer’s researcher and a recently retired executive vice president at Lilly.
Beyond the setback for Lilly, the study raises questions about a leading hypothesis of the cause of Alzheimer’s and how to treat it. The idea, known as the amyloid hypothesis, says the disease occurs when a toxic protein, beta amyloid, accumulates in the brain. The idea is that if beta amyloid levels are reduced, the disease might be slowed, halted or even prevented if treatment starts early enough.
The Lilly drug, like most of the more than 100 Alzheimer’s drugs under development, blocks an enzyme, gamma secretase, needed to make beta amyloid. It was among the first shown to broach the blood-brain barrier and reduce levels of beta amyloid in the brain. And, company studies showed, it did reduce amyloid production.
“We did get enough in the brain to have an effect,” said Dr. Eric Siemers, medical director of Lilly’s Alzheimer’s disease team. “Unfortunately, the effect was not what we wanted.”
Now researchers are focused on what went wrong, and why.
Some, like Dr. Lon Schneider, an Alzheimer’s researcher at the University of Southern California, say the drug’s failure may mean the field is rushing off a cliff in its near single-minded focus on blocking the production of amyloid. Dr. Schneider, like most leading Alzheimer’s researchers, consults for a number of drug companies, including Lilly.
The Lilly study’s failure, he said, “chips away at that approach to testing the amyloid hypothesis.”
“We don’t know what the drug targets for Alzheimer’s disease are,” Dr. Schneider said. “We don’t know because we don’t know the causes of Alzheimer’s.”
At the very least, said Dr. P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University, the Lilly result “clearly tells us that our current views may be too simplistic.”
Dr. Doraiswamy said he was not abandoning the amyloid hypothesis. But, he said, “this is a time of major soul searching in the field.”
“What worries me is that we don’t know if this was a toxicity unique to Lilly’s drug and this late-stage population or whether it also applies to similar anti-amyloid therapies given at earlier stages of the disease,” Dr. Doraiswamy said.
The bad news came on the heels of what researchers see as a resurgence of hope in this challenging field. With new cooperation in research they have made advances in diagnosing Alzheimer’s, a disease that used to be uncertain until autopsy.
And those new diagnostic tests are still exciting, researchers said.
PET scans of amyloid plaques in the brain and tests of cerebrospinal fluid can show amyloid accumulation long before people have symptoms of Alzheimer’s disease and, as was recently reported, appear to identify people at high risk of developing the disease. Researchers believe the best time to try to alter the course of the disease is before memory loss — by that time, brain cells are dead or dying and are unlikely to be restored.
At this point, though, when there is no treatment, those tests are primarily a benefit for companies testing new therapies and researchers trying to understand the disease’s progress.
The long journey of semagacestat began more than a decade ago, when Lilly scientists discovered it could block gamma secretase in laboratory experiments. Years of work followed, showing it appeared safe, that it got into the brains of people, that it reduced the production of amyloid in the brain.
Finally, in 2008, Lilly began two large studies of semagacestat, enrolling more than 2,600 people with Alzheimer’s disease. The company did not expect its drug to reverse the disease — patients’ brains were too ravaged for that, said Richard Mohs, Lilly’s team leader in Alzheimer’s research. But it did hope to slow the disease’s progression.
Now, with the abrupt end of the studies, patients will continue to be followed but no one will be taking any more of the drug.
“The fact that people got worse means there is biology we don’t understand,” Dr. Mohs said.
There are several possible explanations.
page 2
One is that the drug altered the functioning of other proteins in the brain and body — it now appears that gamma secretase is involved in the production of about 20 proteins in addition to beta amyloid. Companies, including Lilly, are developing drugs that block gamma secretase from making amyloid but do not have much of an effect on the other proteins.
One company, Bristol-Myers Squibb, says that is what its drug does. Its drug is now being tested in two clinical trials. In one, the participants have Alzheimer’s. In the other, they have memory impairment that falls short of Alzheimer’s dementia and have brain amyloid PET scans and tests of cerebrospinal fluid showing amyloid is accumulating in their brains, indicating that they are likely to go on to develop Alzheimer’s.
“We still like the amyloid hypothesis,” said Charlie Albright, a Bristol-Myers group director in neuroscience biology. The Lilly drug failure “doesn’t affect our enthusiasm about going forward.”
Another possibility is that the enzyme is decreasing production not just of a dangerous form of amyloid, known as a beta 42, but also of another form, a beta 40, that may protect the brain. Companies are developing so-called selective gamma secretase inhibitors, Dr. Paul said, which only block the production of a beta 42.
Companies are also pursuing other ways of reducing amyloid levels in the brain. One, a Lilly drug that uses a monoclonal antibody to block amyloid, is being tested in a large clinical trial.
And companies are pursuing a more difficult target — blocking a protein, tau, that accumulates in dead and dying nerve cells after the disease is under way.
But Alzheimer’s experts worry about the future. The research is extremely expensive — Lilly spent hundreds of millions of dollars on its failed drug — and it can take a decade or more to know if a drug works. It can take even longer if drugs are tested in people with mild symptoms of Alzheimer’s disease or in people who are at high risk but have no symptoms yet — a direction many think is necessary to really make a difference.
“I am certainly concerned that if we see some more failures it will be a harder to convince companies to invest that much money in testing these hypotheses,” Dr. Paul said.
Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai Medical Center, shares that concern.
“Failures certainly don’t build energy and enthusiasm,” he said. “The market is still there, but failures do take their toll.”
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