A Life's Quest for an Alzheimer Cure

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A Life's Quest for an Alzheimer Cure

February 10, 2016

February 10, 2016

For 7-year-old Paul David Coleman, the backyard pond was a source of endless fascination — and ultimately would be the place that ushered him into the world of science and single-cell research.

“There was a pond in the woods back of the house where my parents had a summer place in Connecticut. I would catch tadpoles and dissect frogs to see how they were inside,” he says. Today, at age 86, with a PhD in physiology and psychology from the University of Rochester and a National Institutes of Health fellowship from Johns Hopkins School of Medicine, Coleman hasn’t lost his fascination with slippery, slimy, squishy objects.

As senior scientist and director of the L.J. Roberts Center for Alzheimer’s Research at Banner Sun Health Research Institute in Sun City, Arizona, Coleman has seen his backyard grow into a much bigger pond. The institute houses the world’s premier bank of hu-man brains, which are harvested at high-speed precision from the 50 miles surrounding the center, where the median age is 75.

Rows of heavily monitored freezers line the walls of the research institute, packed with Tupperware containers by the thousands that store high-quality brain tissue. These containers hold out a mighty hope that scientists will soon have the answers to diagnose and treat one of humanity’s most dark and elusive diseases — Alzheimer’s.

From the moment Jim Eberwine, PhD, handed him a rat’s hippocampus during a Cold Springs Harbor Laboratories course on cloning neural genes, Coleman’s passion for unlocking the mysteries of single cells in animal and human brains hasn’t wavered. When his instructor directed him to report back on the gene expression in a block of tissue that contained huge numbers of different cells, Coleman was nonplused. “The idea of grinding up a block of tissue violated my every aesthetic sense, and it made no scientific sense to me to ‘homogenize’ so many distinctive cells — some of which could be healthy and others diseased,” he explains.

One thing led to another, and before long Coleman and his professor had developed a new method for isolating single neurons to study gene expression. Coleman’s next step was to apply the technique to human brains. But he didn’t stop there. Today, the technique he and his team mastered enables researchers to analyze the activity of as many as 20,000 genes within a single cell. As Coleman peeled away the layers of mystery surrounding how genes worked, he became increasingly fascinated with epigenetics — the study of how a person’s genetic code can be altered by the environment; more specifically, how DNA, genes, gene functioning and genetic vulnerabilities are connected to Alzheimer’s disease.

The man who admits to having failed his Quaker kindergarten is today arguably one of the world’s top Alzheimer’s researchers and — true to his convention-shattering discovery in 1979 that revealed that the brain does not stop developing with age — shows no sign of slow-ing down.

In fact, it appears that Coleman’s career launched like a rocket ship after he turned 60. That’s when he became editor in chief of the journal Neurobiology of Aging; was named as one of an elite few to receive the National Institutes of Health Leadership and Excellence in Alzheimer’s Disease research award; and received a $1-million boost for his work from the Alzheimer’s Association as part of the Pioneer Award for Alzheimer’s Disease Research. He is also listed among about 100 researchers and other advocates as a leading supporter of “The National Alzheimer’s Strategic Plan: A Report of the Al-zheimer’s Study Group,” co-chaired by Senators Newt Gingrich and Bob Kerrey, and issued as a call to action in 2009.

It was during his seventh decade that Coleman developed a blood test that is able to predict a future diagnosis of Alzheimer’s — as he says, “not perfectly but better than chance.” The test must undergo replication, clinical trials and FDA approval before it can be made available to doctors and their patients. Currently, Coleman is work-ing with a company that may be able to create a process that makes the test accessible and affordable — about $30 to $40. Unfortunately, funding from the NIH is no longer available to advance this work.

Yet another high-velocity career thrust came again for Coleman at age 80 when he decided to leave the ivy-covered towers of the East — University of Rochester, Johns Hopkins, and the Massachusetts Institute of Technology — and head for the Wild West. Imagine the shift to the outer reaches of the desert for a man born in 1927 in midtown Manhattan to a Wall Street lawyer father and a schoolteacher mother with a socialist bent.

“I haven’t been disappointed for a moment,” he says. “The spirit of collaboration and intellectual interaction here is unlike any other I’ve known.” Coleman explains how science, healthcare and business come together in this new scientific frontier, where there is a shared thirst to propel the biotechnology sector.

Through his work at Banner Sun Health, Coleman is energized by and engaged with fellow researchers at the Translational Genomics Research Institute (TGen) in Phoenix, Mayo, Arizona State University and the University of Arizona to unlock the secrets hidden in Alzheimer’s disease. “With Alzheimer’s, there are two problems that need to be solved: One is accurate and early detection, and the other is more effective interventions,” Coleman says.

It appears that with his work, we are well on our way. For this vexing disease — in which symptoms may begin when a person is in her 20s, yet precise diagnosis cannot be made until after death — recent work by Coleman and his research group could lead to a simple blood test that may one day alert healthy people to the fact that they are in the earliest stages of the disease.

But a diagnostic test is of little value when there are no known treatments to slow or stop the disease. As a practical man, Coleman feels that a dual focus on detection and intervention go hand in glove. “We want to be able to detect the disease before there are symptoms, then stop or slow its progression sufficiently so that the person can live out his or her normal life span without ever showing symptoms,” he explains. Coleman’s singular focus is on the adult brain — three pounds of spongy tissue, complete with 100 billion neurons and 100 trillion synapses.

Some 5,000,000 Americans are living with Alzheimer’s disease today, and, with an aging population, that number is predicted to leap to 16 million by 2020. According to the Alzheimer’s Association, out of the top 10 causes of death in the U.S., it is the only affiction with no way to prevent it, cure it or even slow its progression.

It can bring tremendous suffering to those afflicted — and, ultimately, early death. The disease cost the U.S. about $203 billion in 2013. Without effective interventions, that number is expected to rise by 500 percent to $1.2 trillion by 2050 — an amount that will not only bankrupt families but could also pose financial devastation for the nation.

The disease is considered an incurable form of dementia, a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. These symptoms result from accumulations of amyloid plaques and neurofibrillary tangles in the brains. Beta-amyloid protein deposits cause amyloid plaques that gather in between healthy neurons, damage the membranes of axons and dendrites of neurons and, ultimately, affect brain function.

It was Coleman’s breakthrough study of identical twins, published in PLOS One in 2009 (with fellow researchers Diego Mastroeni, Ann McKee, Andrew Grover and Joseph Rogers), that opened the door to deeper discoveries today. Essentially, the study involved twin male chemical engineers who were examined both pre- and postmortem. One twin tested positive for Alzheimer’s, while the other did not. Both were raised together, with similar educations and lifestyles. The only appreciable difference was that one twin was exposed to a high level of pesticides — the twin diagnosed with Alzheimer’s. For the first time, scientists had reason to believe that, in addition to genetic predispositions, there is an environmental component to Alzheimer’s. The twin study also revealed the significance of the DNA methylation process, an epigenetic mechanism that regulates gene expression through cell division and enables non-genetic factors such as environment, stress and aging to cause changes in DNA. Today, this discovery is an important factor in research aimed at curing cancer.

Coleman and his research part-ners Walter Nieri, M.D., director of the Center for Healthy Aging at Banner Sun Health Research Institute, and Matthew Huentelman, PhD, associate professor at TGen, are currently beating the bushes for funding for a new study that will investigate the effects of stress on healthy aging, Alzheimer’s and other age-associated diseases like obesity, hypertension, diabetes, arthritis and heart disease. “Because snail brains experience stress in a similar way to mammal brains, their findings are potentially analogous to higher-stakes, human-scale scenarios, like trying to absorb important information after hanging out in a crowded conference room while hungry and tired,” he says about recent findings by the University of Exeter.

“With adequate funding, we could have [Alzheimer’s] licked in 10 to 15 years,” Coleman emphasizes. He talks with envy of his experience with researchers in China. “As long as their work is productive, they are assured of the financial support they need. While our country’s budget for R&D has decreased by five percent, theirs has increased by 15 percent.” Coleman speaks with concern about young scientists who love the work but can’t afford to refuse high-paying jobs in the corporate sector. “This country is destroying its seed corn,” he says.

As for Coleman, his eyes remain firmly on the prize — a prize that is clearly within his grasp. Speak for just a moment with Coleman, and it is evident that, for him, the momentum is exhilarating — and the time is right — to find the solution that will stop this stealthy, life-stealing burglar in its tracks.

“Sometimes, you find out new stuff, and sometimes you fail, but every day is a day that the mind can travel so many different paths,” he proclaims as he hurries on to examine the next slimy, squishy thing that will perhaps reveal the solution to one of medical science’s most vexing mysteries.

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This article first appeared in the Spring 2014 edition of BrainWorld, brainworldmagazine.com

 

Written by: Dianne Price