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 Clinical Trials. Show all posts
Showing posts with label Alzheimer's disease Clinical Trials. Show all posts
2010/08/20
More Alzheimer's anti-amyloid therapy failures of the recent past
As seen 20 August 2010 14:00 at bloomberg.com, Lilly Halts Development of Alzheimer's Disease Drug, by Elizabeth Lopatto and Meg Tirrell - Aug 17, 2010 10:20 PM GMT+0200, excerpt:
"...Researchers have announced setbacks with experimental treatments from GlaxoSmithKline Plc and AstraZeneca Plc, both of London; Martek Biosciences Corp., of Columbia, Maryland; New Brunswick, New Jersey-based J&J; Abbott Laboratories of Abbott Park, Illinois; New York-based Pfizer, Medivation Inc. of San Francisco, and Myriad Genetics Inc. of Salt Lake City, Utah, in the past several years, many targeting amyloid.
One of the drugs, Pfizer and J&J’s bapineuzumab, reduced the buildup of amyloid plaque in the brains of patients with Alzheimer’s disease, according to a study published March 1. Patients getting the medicine in the trial, though, didn’t show a clear improvement in mental function.
Elan Product
On Aug. 9, Dublin-based Elan Corp. and Transition Therapeutics Inc. of Toronto said their experimental Alzheimer’s disease drug, ELND005, will move into the final stage of human tests, even though the drug failed to meet an interim study’s main goals of improving patients’ mental status or daily living activities.
The drugs from Pfizer and Elan are in the final stage of testing usually required by the Food and Drug Administration to approve the marketing of new treatments..."
"...Researchers have announced setbacks with experimental treatments from GlaxoSmithKline Plc and AstraZeneca Plc, both of London; Martek Biosciences Corp., of Columbia, Maryland; New Brunswick, New Jersey-based J&J; Abbott Laboratories of Abbott Park, Illinois; New York-based Pfizer, Medivation Inc. of San Francisco, and Myriad Genetics Inc. of Salt Lake City, Utah, in the past several years, many targeting amyloid.
One of the drugs, Pfizer and J&J’s bapineuzumab, reduced the buildup of amyloid plaque in the brains of patients with Alzheimer’s disease, according to a study published March 1. Patients getting the medicine in the trial, though, didn’t show a clear improvement in mental function.
Elan Product
On Aug. 9, Dublin-based Elan Corp. and Transition Therapeutics Inc. of Toronto said their experimental Alzheimer’s disease drug, ELND005, will move into the final stage of human tests, even though the drug failed to meet an interim study’s main goals of improving patients’ mental status or daily living activities.
The drugs from Pfizer and Elan are in the final stage of testing usually required by the Food and Drug Administration to approve the marketing of new treatments..."
Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse
Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse, excellent Senior Journal article says
As seen at: www.seniorjournal.com 29 August 2010 AM Jerusalem time:
Alzheimer's, Dementia & Mental Health: Battle Against Alzheimer’s Disease Hits Wall as Drug Test Stopped; Maybe Plaque Not Cause seniorjournal.com
Note by Alexei Koudinov: Please make a visit to the original publication to appreciate this excellent report, thanks!
Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse
Aug. 19, 2010 – The efforts to prevent or successfully treat Alzheimer’s disease – the disease most feared by senior citizens - with drugs has never advanced very far, but these efforts suffered a major setback this week when Eli Lilly and Company announced it was halting development of semagacestat. This potential treatment for AD was in advanced clinical trials when it was discovered to be making patients worse instead of better. Many see this failure as a major blow to the most popular theory on the cause of the disease.
The Lilly announcement said, “Studies showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.”
"This is disappointing news for the millions of Alzheimer's patients and their families worldwide who anxiously await a successful treatment for this devastating illness," said Jan M. Lundberg, Ph.D., Executive Vice President, Science and Technology, and President, Lilly Research Laboratories. "This is a setback, but Lilly's commitment to beating Alzheimer's will not waver."
Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has also informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies.
In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease.
Semagacestat was designed to reduce the body's production of amyloid beta plaques, which scientists believe play an important role in causing Alzheimer's disease. Semagacestat is believed to block the activity of gamma secretase, an enzyme that is essential to the body's production of amyloid beta plaques, according to the company. It was being tested in two Phase III clinical trials called IDENTITY and IDENTITY-2.
Lilly’s interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened. However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo.
In addition, data showed semagacestat is associated with an increased risk of skin cancer compared with those who received placebo.
Semagacestat was one of many drugs being tested that focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease. Lilly actually has another amyloid-beta compound, solanezumab, in Phase III trials and says this testing will continue.
The company says these two compounds have “different mechanisms of action.” Lilly also has two other compounds in earlier stages of clinical development that will also continue.
Lilly's clinical team will continue to gather and evaluate data from these studies, and will publish the results for the benefit of future Alzheimer's research.
Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety data, including cognitive scores, for at least six months through regularly scheduled follow-up visits with study physicians and modifications of the existing Phase III protocols.
These additional follow-up visits are expected to help answer a number of important questions, including whether the differences between patients who received semagacestat and those who received placebo will continue after semagacestat has been discontinued. Other smaller short-term studies will be stopped and participants will receive appropriate follow-up.
"We are clearly disappointed by the results," said John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer. He said, however, that the company has nearly 70 molecules currently in clinical development.
"Pharmaceutical research always carries risk, as these results show. But it offers as well the potential for tremendous reward for millions of patients who await new medicines. Despite this and other recent setbacks, Eli Lilly and Company remains financially strong and is even more determined to prevail in our quest to provide new treatments for Alzheimer's and other serious diseases," added Lechleiter.
About Alzheimer's disease
Alzheimer's disease is a fatal form of dementia that causes progressive decline in memory and other aspects of cognition. It occurs when billions of neurons in the brain begin dying prematurely. Researchers don't know exactly what causes it, but the leading hypothesis is that amyloid beta plaques play an important role.
About the IDENTITY trials
IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) and IDENTITY-2 are Lilly's Phase III placebo-controlled trials studying semagacestat, a gamma-secretase inhibitor being investigated as a potential treatment to slow the progression of mild to moderate Alzheimer's disease. Both Phase III trials are fully enrolled, with more than 2,600 patients from 31 countries, and include a treatment period of approximately 21 months. An open-label extension study (IDENTITY-XT) is available to all participants completing either study.
All study participants had to be at least 55 years old and meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, with certain assessment scores indicating mild to moderate Alzheimer's disease. Patients with more advanced Alzheimer's disease were not included in the studies.
This article URL
As seen at: www.seniorjournal.com 29 August 2010 AM Jerusalem time:
Alzheimer's, Dementia & Mental Health: Battle Against Alzheimer’s Disease Hits Wall as Drug Test Stopped; Maybe Plaque Not Cause seniorjournal.com
Note by Alexei Koudinov: Please make a visit to the original publication to appreciate this excellent report, thanks!
Eli Lilly’s semagacestat targeted amyloid beta plaques but patients got worse
Aug. 19, 2010 – The efforts to prevent or successfully treat Alzheimer’s disease – the disease most feared by senior citizens - with drugs has never advanced very far, but these efforts suffered a major setback this week when Eli Lilly and Company announced it was halting development of semagacestat. This potential treatment for AD was in advanced clinical trials when it was discovered to be making patients worse instead of better. Many see this failure as a major blow to the most popular theory on the cause of the disease.
The Lilly announcement said, “Studies showed it did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living.”
"This is disappointing news for the millions of Alzheimer's patients and their families worldwide who anxiously await a successful treatment for this devastating illness," said Jan M. Lundberg, Ph.D., Executive Vice President, Science and Technology, and President, Lilly Research Laboratories. "This is a setback, but Lilly's commitment to beating Alzheimer's will not waver."
Lilly is instructing clinical trial investigators for all semagacestat studies to contact study participants as soon as possible and tell them to immediately stop taking the study drug. Study participants or caregivers should call their study physician to schedule their next appointment. Lilly has also informed regulatory agencies and is providing instructions to investigators outlining the process for finalizing the studies.
In two pivotal Phase III trials, semagacestat was compared with placebo in more than 2,600 patients with mild-to-moderate Alzheimer's disease.
Semagacestat was designed to reduce the body's production of amyloid beta plaques, which scientists believe play an important role in causing Alzheimer's disease. Semagacestat is believed to block the activity of gamma secretase, an enzyme that is essential to the body's production of amyloid beta plaques, according to the company. It was being tested in two Phase III clinical trials called IDENTITY and IDENTITY-2.
Lilly’s interim analysis showed that, as expected, cognition and the ability to complete activities of daily living of placebo-treated patients worsened. However, by these same measures, patients treated with semagacestat worsened to a statistically significantly greater degree than those treated with placebo.
In addition, data showed semagacestat is associated with an increased risk of skin cancer compared with those who received placebo.
Semagacestat was one of many drugs being tested that focus on amyloid-beta proteins, which are believed to play a critical role in Alzheimer's disease. Lilly actually has another amyloid-beta compound, solanezumab, in Phase III trials and says this testing will continue.
The company says these two compounds have “different mechanisms of action.” Lilly also has two other compounds in earlier stages of clinical development that will also continue.
Lilly's clinical team will continue to gather and evaluate data from these studies, and will publish the results for the benefit of future Alzheimer's research.
Although dosing with semagacestat is being stopped, Lilly plans to continue collecting safety data, including cognitive scores, for at least six months through regularly scheduled follow-up visits with study physicians and modifications of the existing Phase III protocols.
These additional follow-up visits are expected to help answer a number of important questions, including whether the differences between patients who received semagacestat and those who received placebo will continue after semagacestat has been discontinued. Other smaller short-term studies will be stopped and participants will receive appropriate follow-up.
"We are clearly disappointed by the results," said John C. Lechleiter Ph.D., Lilly's chairman and chief executive officer. He said, however, that the company has nearly 70 molecules currently in clinical development.
"Pharmaceutical research always carries risk, as these results show. But it offers as well the potential for tremendous reward for millions of patients who await new medicines. Despite this and other recent setbacks, Eli Lilly and Company remains financially strong and is even more determined to prevail in our quest to provide new treatments for Alzheimer's and other serious diseases," added Lechleiter.
About Alzheimer's disease
Alzheimer's disease is a fatal form of dementia that causes progressive decline in memory and other aspects of cognition. It occurs when billions of neurons in the brain begin dying prematurely. Researchers don't know exactly what causes it, but the leading hypothesis is that amyloid beta plaques play an important role.
About the IDENTITY trials
IDENTITY (Interrupting Alzheimer's Dementia by EvaluatiNg Treatment of AmyloId PaThologY) and IDENTITY-2 are Lilly's Phase III placebo-controlled trials studying semagacestat, a gamma-secretase inhibitor being investigated as a potential treatment to slow the progression of mild to moderate Alzheimer's disease. Both Phase III trials are fully enrolled, with more than 2,600 patients from 31 countries, and include a treatment period of approximately 21 months. An open-label extension study (IDENTITY-XT) is available to all participants completing either study.
All study participants had to be at least 55 years old and meet the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's disease, with certain assessment scores indicating mild to moderate Alzheimer's disease. Patients with more advanced Alzheimer's disease were not included in the studies.
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