Mining the genome of hundreds of Alzheimer’s patients and their family members is one of those scientifically risky, large-scale projects that traditional funding mechanisms would typically balk at funding. But it was just the kind of project that Cure Alzheimer’s Fund (CAF) was looking for when it formed in 2005 with the solitary purpose of supporting promising research that will lead to a cure. That year, CAF’s founders asked Massachusetts General Hospital’s Rudolph E. Tanzi, PhD, to lead a consortium of researchers at MGH and nationwide which would collaborate on the Alzheimer’s Genome Project and future projects following its completion in 2008. That year, Time named the project one of the top-10 medical breakthroughs of the year.
“We knew Dr. Tanzi was our man,” recalls Henry McCance, a Boston venture capitalist who says that in starting CAF, he and his fellow founding members “took a venture capital approach to funding — identify the truly talented people and invest so they can turn their brilliant ideas into reality, into a real commodity that the market needs.”
Mr. McCance and his wife Allison, who was diagnosed 10 years ago with early-stage Alzheimer’s, were one of CAF’s three found-ing families, along with Jeff and Jacqui Morby and Phyllis and Jerry Rappaport.
“After meeting Rudy, I came home and I couldn’t sleep,” recalls Phyllis Rappaport. “I thought: we’ve come a long way with cancer and heart disease, so people are going to be sticking around longer — and they’re going to get Alzheimer’s.” The Rappaports have funded other MGH initiatives outside of their giving through CAF, and Phyllis is a founding member of the hospital’s President’s Council, a philanthropic body of community leaders, as well as a member of the MGH Research Advisory Council.
The trio of families knew Dr. Tanzi had been part of the small Mass General team that discovered the gene implicated in Huntington’s disease when he was a 22-year-old lab technician in the lab of James Gusella, PhD, only five years his senior, in 1983. The discovery was the first time a link had been found between a particular disease and its genetic underpinnings, and it sparked the Human Genome Project which led to the sequencing of the entire human genome. They also knew that Dr. Tanzi had discovered three of the four genes discovered that were implicated in early-onset Alzheimer’s.
Dr. Tanzi came to focus on Alzheimer’s quite by accident, however. As a doctoral student, he built a genetic map of chromosome 21,
of which everyone has two copies; Down syndrome is caused when a person has an extra (third) copy of it. He had learned that brain tissue samples of individuals with Down syndrome had plaques similar to the plaques of Alzheimer’s patients. “That made me think, ‘If there were a gene for Alzheimer’s, it would be on chromosome 21.’ That intrigued me and set me off on a path that I’ve been on ever since,” recalls Dr. Tanzi.
In the years when the Alzheimer’s scientific community was focused on better understanding and exploiting the four known genes implicated in the disease, Dr. Tanzi was one of few researchers advocating for finding others. By design, CAF’s founders — who had spent their careers in venture capital, banking and real estate — had established that the organization would do away with the red tape and reams of paperwork required for most grant proposals. And that modus operandi has resonated with the thousands of other donors who give to CAF.
In addition to funding the Alzheimer’s Genome Project, CAF has supported the work of other MGH researchers and more than 40 research papers in all. Its giving to Mass General has totaled more than $6 million in the last five years. With its first flagship project behind it, CAF’s new objective is enabling Dr. Tanzi and his consortium of researchers, with colleagues at MGH, to translate that gold mine of genetic information into drug discovery.
“Our objective now is to take advantage of all these new valuable insights that hold the key to a cure,” says Jeff Morby. “But that will take lots more money than we’ve invested so far.”