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SAN FRANCISCO, California /
San Francisco Chronicle / Health / May 7, 2009
By Victoria Colliver, Chronicle Staff Writer
Peter and Judy Hebert of San Anselmo are on the front lines of Alzheimer's disease research, with Peter participating in a number of clinical trials and continuing two approved therapies for the symptoms of the devastating brain disorder since his diagnosis seven years ago at age 62.
Peter (left) and Judy talk about their many adventures in the living room of their home. Peter Hebert is struggling with Alzheimer's and has gone through a number of different medications including a phase 3 vaccine trial. He lives with his wife Judy in San Anselmo, CA. (Brant Ward / The Chronicle)
He doesn't know if he's on the placebo or the real treatment, but Peter Hebert returned to UC San Francisco on Monday for his fifth infusion of what may be a promising new immunotherapy developed by the South San Francisco lab of Elan Pharmaceuticals, which is now in advanced-stage clinical trials.
Judy Hebert doesn't know if the trial is helping her beloved husband of 44 years, whom she now has to help put on his shoes and finish his sentences. But they know they have to keep trying possible new treatments because there are currently no drugs on the market that target the underlying causes of the disease.
Judy Hebert, helping husband Peter with his shoes, believes that his participation in drug trials and therapies will benefit the next wave of patients. (Brant Ward / The Chronicle)
"There isn't any cure for this, so you're just hoping you'll fall into something that's effective," Judy Hebert said as she described her husband's grace in handling his diagnosis and inevitable decline. "There's also the feel-good aspect. You're contributing, making it easier for your neighbors and children who may face this disease. The tsunami is coming."
The tsunami Hebert was referring to is the wave of Baby Boomers who are getting older, making them more likely to develop the devastating brain disease, which is characterized by memory loss, paranoia and confusion and is ultimately fatal.
Already, 5 million Americans suffer from the disease, but that number is expected to triple by 2050 as the population ages. Alzheimer's is the sixth leading cause of death for Americans, with 1 out of every 8 of those older than 65 being diagnosed with the disease.
"This is a rapidly expanding, daunting problem. We have the Baby Boomers, who are reaching the highest age of risk for this disease and, at the same time, a health care system that is not prepared at all to deal with it," said Dr. Lennart Mucke, director of the UCSF-affiliated Gladstone Institute of Neurological Disease.
Mucke, also a UCSF neurology and neuroscience professor, is one of the leading Alzheimer's experts featured in the four-part HBO series "The Alzheimer's Project," which premieres Sunday.
In addition to addressing the life-changing aspects of the disease, the series looks at cutting-edge research, much of which is centered in the Bay Area. At least a half-dozen clinical trials for Alzheimer's drugs are being conducted at the UCSF Memory and Aging Center, and important research is being done at Stanford University, UC Davis and other local institutions.
Of the more than 90 Alzheimer's drugs in development, the series focuses on the trial drug Peter Hebert may be taking, the hopeful new therapy developed by the pharmaceutical company Elan in collaboration with drugmaker Wyeth.
The drug, bapineuzumab, is in Phase III clinical trials involving 4,000 patients in the United States and Europe, making it the largest Alzheimer's study to date.
The treatment targets the buildup of lumps of protein fragments called amyloid beta peptides, which is the dominant theory of the cause of Alzheimer's. In a normal brain, these fragments are broken down and eliminated. But in an Alzheimer's patient's brain, the amyloid beta accumulates and is responsible for the hard plaques associated with the disease.
The second key pathological hallmark of the disease is the tangles of another protein called tau. The amyloid plaques and tangles, which were first identified by German physician Alois Alzheimer a century ago, appear to block the transmission of electrical messages between nerve cells and eventually kill brain cells. Elan's new drug tests whether introducing antibodies, which attach to the "bad" amyloid, could stimulate the body's immune system to clear that buildup of amyloid beta peptides from the brain tissue.
Elan's chief scientific officer, Dr. Dale Schenk, who is also featured in the HBO series, couldn't give an exact timetable because the trial continues to enroll patients. Still, he remained confident that a true treatment for the disease is imminent.
"I know it couldn't be soon enough for the patient, but it's finally within a relatively short time horizon," he said. "Globally, in three to five years, we'll know much more about the potential role of beta amyloid in the treatment of Alzheimer's disease."
But while amyloid beta peptides are behind the prevailing theory, the latest research indicates Alzheimer's has a variety of causes. That means a variety or combinations of medications will be needed to treat the disease, much in the same way a complex array of therapies is needed to combat cancer.
The Gladstone Institute's Mucke said a number of other issues, including genetics, inflammation and vascular changes, play significant roles in Alzheimer's.
In genetic research, scientists have identified a protein called apolipoprotein, or apoE, which helps carry cholesterol and fat.
People carry three common types of apoE - E2, E3 and E4 - but those who inherit one or two apoE4 genes from their parents appear to have an increased risk of developing Alzheimer's. Scientists are trying to develop drugs that target the detrimental effects of apoE4.
The tau protein is also an important area of research. Researchers are trying to block the effect of overexcited tau and its ability to form tangles, Mucke said.
He is also testing a theory involving Alzheimer's and epilepsy. Alzheimer's patients appear to have an unusually high incidence of silent epileptic-like seizures. Mucke and his team recently began a study that looks at the electrical brain activity of Alzheimer's patients, with the hope that anti-seizure drugs may help some patients.
Vascular problems and inflammation also appear to be factors in developing Alzheimer's. Vascular changes association with heart disease, diabetes, hypertension and other conditions appear to restrict normal blood flow to the brain, which in turn inhibits its efficiency and ability to rid itself of those bad amyloids, Mucke said.
With inflammation, the theory is the buildup of proteins in an Alzheimer's patient's brain irritates immune cells and puts them into overdrive, causing a chronic inflammatory response. Researchers are looking into ways to "cool" this process, but so far the use of anti-inflammatory medications for on Alzheimer's has not been encouraging, Mucke said.
While much progress has been made, research and funding for Alzheimer's is far behind that of cancer, heart disease and other conditions, Mucke said. But he hoped, with increased public awareness and government involvement, that will change.
"There's no ACT UP for Alzheimer's disease," Mucke said, referring to the AIDS organization known for using civil disobedience and other tactics to deliver its message. "In part, the reason for this is the people who have this disease can't speak up for themselves."
Preventing Alzheimer's disease?
Many risk factors for Alzheimer's disease, mainly age and genetics, cannot be controlled. Until new treatments become available that can prevent or even cure Alzheimer's, health experts recommend maintaining a heart-healthy diet and active lifestyle - which research has shown may reduce the risks of developing the disease. Other recommendations include:
-- Lowering levels of cholesterol and homocysteine, an amino acid in blood
-- Lowering high blood pressure
-- Controlling diabetes
-- Exercising regularly
-- Engaging in social and intellectually stimulating activities
Source: National Institute on Aging
The treatments
Five drugs have been approved by the U.S. Food and Drug Administration to treat Alzheimer's disease, although all are limited to managing the symptoms rather than targeting the underlying cause. Four of the drugs are cholinesterase inhibitors, which work to increase levels of acetylcholine, a chemical messenger involved in memory and other thought processes:
-- Aricept (donepezil): Approved in 1996, this once-a-day medication is the most popular Alzheimer's drug and is approved to treat all stages of the disease.
-- Razadyne (galantamine): Approved for mild to moderate stages.
-- Exelon (rivastigmine): Also approved for mild to moderate stages.
-- Cognex (tacrine): Approved in 1993, this first drug to treat Alzheimer's is generally no longer used because of side effects, such as liver damage.
One drug is in a class of its own, called an NMDA receptor antagonist. The drug works to regulate the activity of glutamate, a chemical involved in storing and retrieving information from the brain:
-- Namenda (memantine): Approved in 2003 to treat moderate to severe forms of the disease.
Source: Alzheimer's Association
Victoria Colliver
vcolliver@sfchronicle.com.
© 2009 Hearst Communications Inc.
Peter (left) and Judy talk about their many adventures in the living room of their home. Peter Hebert is struggling with Alzheimer's and has gone through a number of different medications including a phase 3 vaccine trial. He lives with his wife Judy in San Anselmo, CA. (Brant Ward / The Chronicle)
He doesn't know if he's on the placebo or the real treatment, but Peter Hebert returned to UC San Francisco on Monday for his fifth infusion of what may be a promising new immunotherapy developed by the South San Francisco lab of Elan Pharmaceuticals, which is now in advanced-stage clinical trials.
Judy Hebert doesn't know if the trial is helping her beloved husband of 44 years, whom she now has to help put on his shoes and finish his sentences. But they know they have to keep trying possible new treatments because there are currently no drugs on the market that target the underlying causes of the disease.
Judy Hebert, helping husband Peter with his shoes, believes that his participation in drug trials and therapies will benefit the next wave of patients. (Brant Ward / The Chronicle)
"There isn't any cure for this, so you're just hoping you'll fall into something that's effective," Judy Hebert said as she described her husband's grace in handling his diagnosis and inevitable decline. "There's also the feel-good aspect. You're contributing, making it easier for your neighbors and children who may face this disease. The tsunami is coming."
The tsunami Hebert was referring to is the wave of Baby Boomers who are getting older, making them more likely to develop the devastating brain disease, which is characterized by memory loss, paranoia and confusion and is ultimately fatal.
Already, 5 million Americans suffer from the disease, but that number is expected to triple by 2050 as the population ages. Alzheimer's is the sixth leading cause of death for Americans, with 1 out of every 8 of those older than 65 being diagnosed with the disease.
"This is a rapidly expanding, daunting problem. We have the Baby Boomers, who are reaching the highest age of risk for this disease and, at the same time, a health care system that is not prepared at all to deal with it," said Dr. Lennart Mucke, director of the UCSF-affiliated Gladstone Institute of Neurological Disease.
Mucke, also a UCSF neurology and neuroscience professor, is one of the leading Alzheimer's experts featured in the four-part HBO series "The Alzheimer's Project," which premieres Sunday.
In addition to addressing the life-changing aspects of the disease, the series looks at cutting-edge research, much of which is centered in the Bay Area. At least a half-dozen clinical trials for Alzheimer's drugs are being conducted at the UCSF Memory and Aging Center, and important research is being done at Stanford University, UC Davis and other local institutions.
Of the more than 90 Alzheimer's drugs in development, the series focuses on the trial drug Peter Hebert may be taking, the hopeful new therapy developed by the pharmaceutical company Elan in collaboration with drugmaker Wyeth.
The drug, bapineuzumab, is in Phase III clinical trials involving 4,000 patients in the United States and Europe, making it the largest Alzheimer's study to date.
The treatment targets the buildup of lumps of protein fragments called amyloid beta peptides, which is the dominant theory of the cause of Alzheimer's. In a normal brain, these fragments are broken down and eliminated. But in an Alzheimer's patient's brain, the amyloid beta accumulates and is responsible for the hard plaques associated with the disease.
The second key pathological hallmark of the disease is the tangles of another protein called tau. The amyloid plaques and tangles, which were first identified by German physician Alois Alzheimer a century ago, appear to block the transmission of electrical messages between nerve cells and eventually kill brain cells. Elan's new drug tests whether introducing antibodies, which attach to the "bad" amyloid, could stimulate the body's immune system to clear that buildup of amyloid beta peptides from the brain tissue.
Elan's chief scientific officer, Dr. Dale Schenk, who is also featured in the HBO series, couldn't give an exact timetable because the trial continues to enroll patients. Still, he remained confident that a true treatment for the disease is imminent.
"I know it couldn't be soon enough for the patient, but it's finally within a relatively short time horizon," he said. "Globally, in three to five years, we'll know much more about the potential role of beta amyloid in the treatment of Alzheimer's disease."
But while amyloid beta peptides are behind the prevailing theory, the latest research indicates Alzheimer's has a variety of causes. That means a variety or combinations of medications will be needed to treat the disease, much in the same way a complex array of therapies is needed to combat cancer.
The Gladstone Institute's Mucke said a number of other issues, including genetics, inflammation and vascular changes, play significant roles in Alzheimer's.
In genetic research, scientists have identified a protein called apolipoprotein, or apoE, which helps carry cholesterol and fat.
People carry three common types of apoE - E2, E3 and E4 - but those who inherit one or two apoE4 genes from their parents appear to have an increased risk of developing Alzheimer's. Scientists are trying to develop drugs that target the detrimental effects of apoE4.
The tau protein is also an important area of research. Researchers are trying to block the effect of overexcited tau and its ability to form tangles, Mucke said.
He is also testing a theory involving Alzheimer's and epilepsy. Alzheimer's patients appear to have an unusually high incidence of silent epileptic-like seizures. Mucke and his team recently began a study that looks at the electrical brain activity of Alzheimer's patients, with the hope that anti-seizure drugs may help some patients.
Vascular problems and inflammation also appear to be factors in developing Alzheimer's. Vascular changes association with heart disease, diabetes, hypertension and other conditions appear to restrict normal blood flow to the brain, which in turn inhibits its efficiency and ability to rid itself of those bad amyloids, Mucke said.
With inflammation, the theory is the buildup of proteins in an Alzheimer's patient's brain irritates immune cells and puts them into overdrive, causing a chronic inflammatory response. Researchers are looking into ways to "cool" this process, but so far the use of anti-inflammatory medications for on Alzheimer's has not been encouraging, Mucke said.
While much progress has been made, research and funding for Alzheimer's is far behind that of cancer, heart disease and other conditions, Mucke said. But he hoped, with increased public awareness and government involvement, that will change.
"There's no ACT UP for Alzheimer's disease," Mucke said, referring to the AIDS organization known for using civil disobedience and other tactics to deliver its message. "In part, the reason for this is the people who have this disease can't speak up for themselves."
Preventing Alzheimer's disease?
Many risk factors for Alzheimer's disease, mainly age and genetics, cannot be controlled. Until new treatments become available that can prevent or even cure Alzheimer's, health experts recommend maintaining a heart-healthy diet and active lifestyle - which research has shown may reduce the risks of developing the disease. Other recommendations include:
-- Lowering levels of cholesterol and homocysteine, an amino acid in blood
-- Lowering high blood pressure
-- Controlling diabetes
-- Exercising regularly
-- Engaging in social and intellectually stimulating activities
Source: National Institute on Aging
The treatments
Five drugs have been approved by the U.S. Food and Drug Administration to treat Alzheimer's disease, although all are limited to managing the symptoms rather than targeting the underlying cause. Four of the drugs are cholinesterase inhibitors, which work to increase levels of acetylcholine, a chemical messenger involved in memory and other thought processes:
-- Aricept (donepezil): Approved in 1996, this once-a-day medication is the most popular Alzheimer's drug and is approved to treat all stages of the disease.
-- Razadyne (galantamine): Approved for mild to moderate stages.
-- Exelon (rivastigmine): Also approved for mild to moderate stages.
-- Cognex (tacrine): Approved in 1993, this first drug to treat Alzheimer's is generally no longer used because of side effects, such as liver damage.
One drug is in a class of its own, called an NMDA receptor antagonist. The drug works to regulate the activity of glutamate, a chemical involved in storing and retrieving information from the brain:
-- Namenda (memantine): Approved in 2003 to treat moderate to severe forms of the disease.
Source: Alzheimer's Association
Victoria Colliver
vcolliver@sfchronicle.com.
© 2009 Hearst Communications Inc.
