Can Venture Capital Help Cure Alzheimer’s Disease?

A Pittsburgh philanthropist and retired Mellon exec thinks so
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In 1988, Jeffrey L. Morby left American Express to join the management team tapped to rescue the nearly bankrupt Mellon Bank. After helping turn Mellon around, he retired at 59, but Morby has hardly been wiling away the time.

He and his wife, Jacqueline, have been putting their corporate and venture capital acumen to use in trying to find a cure for Alzheimer’s disease. “I can’t think of anything more important than finding a cure for Alzheimer’s,” Morby said. “I actually think there is a good chance we’ll get there in five years.”

More than 5.4 million Americans have the unrelenting disorder that attacks the brain’s nerve cells, stealing memory and ability to think and communicate. While deaths from heart disease and cancer are on the decline, Alzheimer’s deaths are increasing. With a graying country, Alzheimer’s is projected by 2050 to affect more than 15 million Americans and cost the nation $1.1 trillion. To stem this tide, President Barack Obama recently announced plans to find effective preventions and treatments by 2025. The president’s proposed FY 2013 budget provides an additional $80 million in Alzheimer’s research.

Long-​time philanthropists, the Morbys decided in 2004 to focus on one cause. This decision came after Morby met the one man who, he thinks, may hold the key to a cure — Harvard’s Rudy Tanzi, Ph.D. Tanzi was the first scientist to discover or co-​discover three of the genes associated with Alzheimer’s. Morby met him while researching a book on the mysteries of the human brain (the book is now on hold). He had heard from an old Harvard friend that no one knew more about the brain than Tanzi, so Morby went to interview him. “During our conversation, Alzheimer’s came up,” Morby recalled. “Tanzi said the Human Genome Project has provided us with the tools for potentially curing many diseases, including Alzheimer’s, and yet there’s no money going to take advantage of this technology.”

By meeting’s end, Morby was convinced that curing Alzheimer’s should be the target of a new nonprofit foundation, founded by the Morbys and employing a “philanthropic venture-​capital strategy.” A very successful venture capitalist in her own right, Jacqueline knows the toll of Alzheimer’s through her mother’s diagnosis.

The Morbys contacted Boston-​area friends and soon had three families who shared their business savvy and willingness to make a mark. Pooling their investments, the families started Pittsburgh-​based Cure Alzheimer’s Fund (cure​alz​.org). “We decided at the outset that we’d use the same management techniques as entrepreneurs starting a new company,” Morby said. And while some foundations work for a return on investment, he added, “we decided in the beginning we were not interested in making money with our funding. We were interested in finding a cure.”

Since the fund’s inception, the Morbys, along with more than 4,000 other families (many from the Pittsburgh area), have invested $15 million in 50 Alzheimer’s research projects at 24 major institutions, resulting in 100 papers being published in major scientific journals. The Morbys, along with the other founding families, pay the fund’s overhead, so every bit donated by the public can go to research — a facet of philanthropy practiced by few other nonprofits.

Much of the research money ($6 million) went to a key achievement — the Alzheimer’s Genome Project — that identified more than 100 genes believed to be associated with Alzheimer’s. In 2008, Time magazine called the discovery of Alzheimer’s genes one of the year’s top 10 medical breakthroughs.

Until 2005, only four Alzheimer’s genes had been identified (three co-​discovered by Tanzi and another by a Duke University researcher). “Because of his knowledge, Tanzi knew that there were many more Alzheimer’s genes that hadn’t been discovered, so we felt, to really get a handle on this disease, we needed to identify all of these genes,” Morby said. “So we funded the largest genomic scan organized around a single disease ever done and provided the raw materials for understanding the disease.”

Morby has an MBA from Harvard and an engineering degree from Stanford, and though he spent most of his career in the corporate world, he easily navigates scientific conversation. He explained that when genes are first discovered by a genomic scan they are only candidates. “They’re not considered to be a gene unless you know the mechanism of action and have actually found what it does. Until you do that, you can’t say it’s a true gene, but only that it has a high correlation with Alzheimer’s.”

A significant number of the candidate genes may have protective potential. But first, researchers have to do the “translational analysis.” In other words, Morby said, “understand what the gene does before you can stop it or jack up its positive effect.” This is a major focus of current research activities.

Cure Alzheimer’s is also funding another key project known as AlzGene (alz​gene​.org), the world’s largest database of Alzheimer’s research information. (Similar databases exist for Parkinson’s and several other diseases.) “So anywhere in the world, if someone does a research study that has to do with Alzheimer’s, we pick it up, organize it by gene, and provide information about that study and make it free and online to the world.”

Researchers have unearthed interesting discoveries in recent years, including clues that Alzheimer’s is likely an autoimmune disease — the result of the body’s way of protecting the brain from pathogens by cloaking them in fatty plaques known as beta-​amyloid. Combine this immune response with faulty genes, the theory goes, and too much plaque gets produced, erasing memory.

Already, researchers have confirmed the “mechanisms of action” of several key Alzheimer’s genes, thereby readying them for drug discovery and helping bring about a third generation of Alzheimer’s drugs. “We have three very encouraging potential preventatives… some of them pretty far along,” Morby said. “These drugs that we are potentially identifying could probably stop [the progression of Alzheimer’s] or maybe reverse it a little bit…”

One drug the Morbys are banking on would work like a statin, where dosage is adjusted depending on cholesterol levels, but in this case it would target beta-​amyloid plaque levels. But first scientists have to figure out how to measure amyloid efficiently — not an easy task. A University of Pittsburgh team has made groundbreaking progress in that area. In 2010, Co-​Director of UPMC’s Alzheimer Disease Research Center William E. Klunk, M.D., Ph.D., got $300,000 from the Cure Alzheimer’s Fund — the first grant to go to a Pittsburgh project. His grant was the result of the fund’s targeted business plan. It doesn’t accept proposals from researchers or put them through a peer-​review process that can take two years. Instead, the fund’s panel of experts actively seeks the world’s best researchers and funds them. As Klunk told one reporter, “I’ve never seen a foundation move so fast to funding.”

Klunk co-​discovered the breakthrough called Pittsburgh Compound B or PiB — the first chemical to image beta-​amyloid in the brain safely, allowing scientists to see the plaque buildup in someone living with Alzheimer’s. Before this breakthrough a decade ago, the hallmark physical sign of Alzheimer’s could only be seen after death, during an autopsy. GE Healthcare is pursuing the development of a clinical diagnostic agent based on Pitt’s research. Klunk and Tanzi are sharing the Cure Alzheimer’s Fund grant to create new therapies and biomarkers based on newly created compounds, which have significant potential due to their ability to cross the blood brain barrier and both to react with amyloid and to serve as biomarkers for amyloid. Klunk is producing new compounds, which Tanzi’s lab in Boston tests to see whether they are promising candidates.

Despite an ambitious goal, Cure Alzheimer’s Fund financing represents a drop in the bucket of the investment needed to get a new drug to millions of Alzheimer’s patients. Any promising compound would need to get picked up by a pharmaceutical company, Morby said, which “would have the hundreds of millions of dollars needed to bring it to market. We are in constant contact with pharmaceutical companies, eager to take our research to the next step.”

Kelly Casey

Kelly loves telling people’s stories. She began her journalism career at the Pitt News, University of Pittsburgh’s student newspaper. For several years, she was a general assignment and Sunday feature writer for the Pittsburgh Tribune-​Review. After moving to Virginia, she joined the University of Virginia Medical Center marketing department. For the past several years, she has focused on health writing, including serving as regional editor for the nationally syndicated quarterly magazine, Vim & Vigor. She was lulled back to Western Pennsylvania in 2006 but continues to work for UVA from afar and is excited to be once again reporting on the Pittsburgh region. Kelly lives in Oakmont with her husband and two sons.

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