In the cool morning hours of April 20, Lloyd and Mary McCreary rose before dawn and headed to Emory University Hospital, a seven-mile drive from their home in Chamblee.
Less than two hours later, Mary said goodbye to her husband and headed to a third-floor operating room. There, neurosurgeon Nicholas Boulis drilled two nickel-size holes into the top of her head. Based on a computer generated random assignment, he might or might not have implanted a gene therapy drug that researchers hope will stave off memory loss in patients with Alzheimer’s disease.
The CERE-110 trial is one of several significant research projects under way at Emory University’s Alzheimer’s Disease Research Center that experts hope will slow or arrest the disease’s progression. Others are focused on early detection, such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI), which tests brain imaging techniques.
“We have to have the early detection in order to use treatments when they are most effective, and we have to have treatments that will have a real impact on preventing and slowing the disease,” said Dr. James Lah, the research center’s clinical core director. “We absolutely have to have both in order to be successful.”
Four years into her illness, Mary McCreary can’t always remember how to spell her name or where she was born, but volunteering for the CERE-110 trial has given her hope.
“It was something I had control over,” she said recently.
When she learned she qualified for the CERE-110 trial, the 57-year-old accountant didn’t hesitate to sign up.
Still, the prospect of drilling two holes in his wife’s head gave Lloyd McCreary pause. But as the couple came to know Dr. Lah, the McCrearys grew confident that the potential benefits of the trial far outweighed the risks.
Emory is one of about 30 federally sponsored Alzheimer’s disease research centers where such diagnostic methods and treatments are being developed and tested. What sets it apart from other research centers is that it not only conducts scientific studies and trials, it also treats patients, giving patients access to cutting-edge research and care.
McCreary is one of four local volunteers — and some 50 across the country between the ages of 50 and 80 with mild to moderate Alzheimer’s symptoms — who are enrolled in the trial. As is typical of clinical trials, half of the participants receive CERE-110 and the other half receive a placebo.
McCreary doesn’t know if she got the drug. “But it doesn’t matter,” she said.
The good news is, once the study is completed in 2012, if the results are promising, participants in the placebo group will be eligible to be treated with CERE-110.
“It’s exciting,” said Allan Levey, director of the center and chairman of the department of neurology at Emory’s School of Medicine. “There’s never been a more promising time when we have all the tools available to really make a difference.”
New urgency
Alzheimer’s research has taken on new urgency as the scope of the Alzheimer’s crisis magnifies. Some 5.4 million Americans have the irreversible brain disease, and the numbers will rise as baby boomers age. Nearly one in two Americans will get an Alzheimer’s diagnosis by age 85.
“Among aging boomers, the words ‘Alzheimer’s disease’ is supplanting cancer as the most feared word in the medical lexicon,” said Lah.
He and other researchers believe the way to successfully manage the looming pandemic among aging populations is to develop treatments that can be applied very early to slow down the course of the illness.
The Emory team has made steady gains in recent years toward developing tests to detect the earliest signs of Alzheimer’s or mild cognitive impairment, a milder form of dementia, up to 10 years before the first symptoms emerge.
“Just as we currently use screening mammograms or colonoscopies to detect early breast cancer or colon cancer, we hope to be applying tests to detect the earliest stages of Alzheimer’s disease at a point well before severe memory loss occurs,” Levey said. “Rather than waiting for someone to get lost or become forgetful, we really want to be able to identify risk factors if they are present before the symptoms appear.
“Current research treatments are using people who already have symptoms,” he said. “In the future, we envision treatment trials before any symptoms begin. And, in fact, we think that will likely be more effective as a primary prevention. We have to know who is going to get the disease in order to do research to test if we can prevent it.”
Currently, some 500 research volunteers, including Mary McCreary, are participating in Alzheimer’s-related projects at Emory that will help investigators determine if some treatments are effective and safe.
However, Levey said, finding those answers takes time and money, neither of which is in great abundance.
“We don’t have time because the crisis is upon us,” he said. “There is a tsunami of people aging before our eyes, and we don’t have anywhere near the financial support necessary to test all the excellent ideas.”
The CERE-110 study, one of a small number of projects that managed to survive the National Institutes of Health funding gauntlet, is being conducted with roughly $5 million from the federal agency and support from the small biotech company Ceregene, maker of the drug.
Still, Levey said that nine out of 10 of the best ideas for new treatments will not have sufficient funding available to be tested.
“That means we’re leaving the answer right on the table,” he said.
Recent discoveries
Twenty years ago, doctors would have assumed McCreary’s memory loss was a result of normal aging. There would not have been any treatment. Indeed, there probably would not have been an evaluation.
“The care would’ve focused on supportive care and treating symptoms,” said Janet Cellar, a clinical nurse specialist and administrative director of the research center.
But recent research has shown that groups of individuals with isolated memory problems who are otherwise functional could be classified as suffering from mild cognitive impairment. And although there are many reasons why people might have these mild impairments, it’s more often than not a harbinger of Alzheimer’s disease.
One of the challenges, Lah said, has been to determine whether an individual with mild cognitive impairment is on a path to Alzheimer’s disease. Twenty years ago the answer to that would have been wait until the person dies, get his or her brain and look at it under a microscope. But advances in research have allowed scientists to develop tests to measure some of the Alzheimer’s related changes in a living individual. That’s where studies such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI), under way at Emory and 51 other sites across the country, come into play.
“The goal was to understand what were the normal changes associated with aging and what were the very earliest indicators of the beginning of a neurodegenerative process based on brain imaging, blood and spinal fluid tests,” said Cellar, who is leading the Emory initiative along with Levey.
If they could figure that out they would know when to initiate treatment, thus improving the quality of a patient’s life. And in lieu of a cure, it would allow patients and their families to plan for the future.
Based on ADNI studies, Lah said, researchers have learned that certain changes in cerebral spinal fluid in people who had mild memory loss were very strongly linked to the eventual progression to Alzheimer’s disease.
That was one of the pieces he used to diagnose McCreary early in her illness.
Volunteers participating in the study performed tests during their initial visits and repeated them over time. During that period some individuals who had normal thinking abilities developed memory loss and some developed Alzheimer’s disease.
Knowing those outcomes, researchers were then able to go back and examine various protein levels collected several years earlier and identify pathological factors that would predict the development of Alzheimer’s.
“Those data have now become sufficiently strong enough to support their use in clinical evaluation of patients with memory concerns like McCreary,” Lah said.
‘Taking greater risks’
Just as everyone had hoped, McCreary’s surgery was uneventful.
Except for bouts of nausea immediately following the surgery, McCreary had no complications even though there was a 1 percent to 2 percent chance the surgery could have caused a brain hemorrhage. In fact, she had so little pain after the surgery she took only a single aspirin. She went home early the next day.
In Alzheimer’s disease, brain cells involved in memory and cognition die off. The goal of the CERE-110 gene therapy is to boost production of a naturally occurring protein that might prevent cell death and help neurons grow new connections.
The gene is delivered by a fragment of a harmless virus implanted by the surgeon deep into the brain. The hope is that the viral fragments will invade brain cells and deliver the gene. The gene then would direct the cells to produce nerve growth.
Gene therapy has been tried for other diseases, including cystic fibrosis, cancer and Parkinson’s disease, but many efforts have failed. It has yet to be approved for general use outside of clinical trials.
In the months since the surgery, the McCrearys have gone back and forth on the question of whether Mary actually received the CERE-110.
If nothing else, they said, they get to see Lah more frequently.
“I usually come in with half a dozen questions and he’s very forthright,” Lloyd McCreary said.
The way Lah sees it, experimental therapies are worth the risk because he and his patients recognize that the alternative, Alzheimer’s slow destruction of the brain, is utterly devastating.
“We’re taking greater risks in part because we have greater confidence in our ability to diagnose and slow down the course of the illness,” Lah said. “Slowing down the disease in effect is going to be the cure for the disease.”
Because Alzheimer’s affects people later in life, he believes slowing its development by roughly five years could potentially cut in half the number of people who have the disease.
“What I always tell people is if I can keep your memory loss from progressing and you’re enjoying an excellent quality of life, when you drop dead of a heart attack at age 95, the cardiologist loses and the neurologist wins and everybody is happy, including the patient,” he said.
“I don’t know anybody who wants to live forever,” Lah said, “but everybody would like for their brains to be working well for as long as they are using them.”
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Special report The Alzheimer’s generation
This month, we bring you revealing coverage of the health crisis that could define the
baby boomer generation. This five-part series provides an intimate look at the toll on caregivers and the burden on personal savings. Today in Part Four, the latest discoveries to manage the disease.
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How we got the stories
Reporters Helena Oliviero and Gracie Bonds Staples spent the last six weeks reading myriad reports, websites and research findings on Alzheimer’s, and interviewing more than three dozen Alzheimer’s patients, caregivers, advocates, doctors and medical researchers.
In addition to Dr. Allan Levey, Dr. James Lah and clinical nurse specialist Janet Cellar, key sources included Ken Hepburn, associate dean for research and director of graduate studies in the Nell Hodgson Woodruff School of Nursing at Emory University; Kevin M. Lynch, assistant professor of insurance at the American College and certified financial planner; and Eric J. Hall, founding president and chief executive officer of the Alzheimer’s Foundation of America.
We want to express our appreciation to the Alzheimer’s patients and their families who generously opened up their homes and their lives to our reporters and photographers for extended periods of time over the course of several days, so our readers could get a better understanding of what it means to live with the disease.
