Unlocking The Secrets Of Alzheimer’s

Like many in his field, Alzheimer’s expert Dr. Frank LaFerla harbored significant doubts.

To LaFerla, a professor of neurobiology and behavior at the University of California, Irvine, stem cells just didn’t see­m like good candidates to treat Alzheimer’s, the cruel disease that robs people of their memory and ultimately leads to death. Like many others, LaFerla thought that stem cells, despite their undeniable promise for a host of other serious medical conditions, would likely never replace enough lost neurons in the brain to appreciably improve cognition in Alzheimer’s sufferers. Unlike many of his colleagues, LaFerla persisted. He knew that only through rigorous experimentation does science yield definitive answers to questions, such as: Do stem cells have the potential to prevent, treat, or even cure Alzheimer’s?

LaFerla’s willingness to think outside the box was nothing new.

Years before, he debunked the myth that nicotine could treat Alzheimer’s. He also discovered that stress hastens the disease’s development in mice. And he also and helped identify a compound —AF267B — that might one day relieve Alzheimer’s symptoms in humans. LaFerla was also the first scientist to develop a mouse model that has both the plaques and tangles associated with the disease, providing researchers with a tool to better understand the relationship between the two. (Since 2003, UC Irvine has provided the model to over 150 investigators in more than 20 countries.) In 2005 LaFerla received the prestigious MetLife Promising Works Award for his Alzheimer’s studies.

“I want to make a difference,” says LaFerla, who devotes more than 70 hours a week to his singular quest of unlocking the secrets of Alzheimer’s, the seventh-leading cause of death in the United States, according to the Alzheimer’s Association.

As many as 5.3 million Americans have Alzheimer’s, a progressive brain disorder that causes significant memory loss that can make it difficult, if not impossible, for sufferers to work, make judgments, socialize normally and carry out daily activities. The number of cases is expected to skyrocket with America’s aging population.

Beta-amyloid is believed to be the main culprit in Alzheimer’s. In healthy people, the brain eliminates excess beta-amyloid; however, in Alzheimer’s sufferers, the protein builds up in the brain and forms clumps known as plaques, which prevent cells in the brain from communicating. At present, Alzheimer’s has no cure. FDA-approved medications that slow the disease’s progression are of limited effectiveness.

See The Mice Run

To test the effectiveness of stem cells against Alzheimer’s disease, LaFerla and UC Irvine colleague Dr. Mathew Blurton-Jones injected mouse neural stem cells into mice genetically engineered to have the equivalent of advanced Alzheimer’s disease. Then they waited. And hoped. About a month later, they subjected the mice to a series of memory tests. Much to their delight, the mice that received the stem cell injections performed markedly better on a memory test. LaFerla and Blurton’s finding showed for the first time that neural stem cells could rescue memory in mice with Alzheimer’s disease, raising hopes of finding a potential treatment for humans.

When the scientists examined the mice brains, they found that just 6 percent of the stem cells had turned into neurons. Nor had the stem cells reduced the number of plaques and tangles. What happened? Turns out the stem cells secreted a protein that created more neural connections, which improved cognitive function by nursing brain cells back to health. “Essentially, the cells were producing fertilizer for the brain,” says LaFerla, who also serves as director of UC Irvine’s Institute for Memory Impairments & Neurological Disorders, or UCI MIND.

In April 2009, the California Institute for Regenerative Medicine (CIRM) awarded LaFerla a $3.6 million grant to develop an Alzheimer’s therapy involving human neural stem cells. That grant, combined with the results of LaFerla’s earlier experiment, arguably places LaFerla at the leading edge of research into stem cells’ efficacy in treating Alzheimer’s. “Dr. LaFerla is an international star known for his pioneering and seminal work with Alzheimer’s disease,” says Domenico Pratico, an Alzheimer’s expert and an associate professor at the Temple University School of Medicine. “His contribution has been and will be enormous.”

LaFerla has led a team of UC Irvine researchers to better understand the link between Alzheimer’s and Parkinson’s. Preliminary research has found that when the proteins behind these neurodegenerative disorders combine, a dramatic decline in cognition often results. This work is generating hope for people with the Lewy body variant of Alzheimer’s, in which Parkinson’s symptoms are also present.

A Happy Accident

LaFerla became an Alzheimer’s researcher almost by accident.

After graduating from the University of Minnesota with a Ph.D. in virology, he headed east with his family to Rockville, Maryland, for a position with the American Red Cross. LaFerla had expected to study HIV. Unbeknownst to him, the scientist he was to support had recently switched to Alzheimer’s, a disease about which LaFerla knew virtually nothing. He felt deeply disappointed.

That all changed after the hard drive on LaFerla’s computer crashed. Suddenly, he put it all together. Alzheimer’s, LaFerla concluded, “happens when the body’s hard drive crashes, and that’s a terrible, terrible thing.” His mother’s death in 1999 from dementia at age 59 only deepened his commitment to try to discover treatments and cures for neurological disorders.

“I have seen firsthand the damage that dementia can cause and the pain it imparts to all involved,” LaFerla says. “My goal is to research ways to make memories last a lifetime.”

What are Stem Cells?

Stem cells are found in all multicellular organisms. They are unspecialized cells that can self-renew and also differentiate into more specialized cells that make up every organ and tissue. Because of stem cells’ unique regenerative abilities, they hold the promise to treat or one day even cure a host of incurable conditions ranging from diabetes and Alzheimer’s disease to cancer and heart disease.

This article was first published in the print edition of Brain World Magazine.

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