The Quest for an Alzheimer’s Cure: An Interview with Dr. Paul Coleman

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 million 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 Coleman cont’d the Alzheimer’s Association, out of the top 10 causes of death in the U.S., it is the only affliction 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. Betaamyloid 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 partners Walter Nieri, M.D., director of the Center for Healthy Aging at Banner Sun Health Research Institute, and Matthew Huentelman, Ph.D., 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.

This article was originally published in the Spring 2014 issue of Brain World Magazine.

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