In Charlestown, Venture Capital Fuels Alzheimer's Research

By Sean Corcoran

Nov. 9, 2010

With no cure on the horizon and few treatments available, the government spends about $170 billion annually caring for Alzheimer's patients. By the year 2050, that cost is expected to rise to $1 trillion annually, with about one million new Azheimer's patients being added each year.

In the second part of our series, "Venture Philanthropy: A Business Approach To Curing Alzheimer's Disease," Sean Corcoran reports on a group of local business leaders whose frustration with the slow pace of government-sponsored research has led them to use their venture capital experience to coordinate some of the nation's top doctors in a search for a way to stop Alzheimer's.

Inside The Research Lab | Photos by Jess Bidgood/WGBH

BOSTON -- In a nondescript building in the Charlestown Navy Yard, Dr. Rudy Tanzi, a Mass General researcher and professor of Neurology at Harvard Medical School, stands in a large lab filled with bays, benches and young research assistants hard at work. Behind Tanzi is a line of half a dozen or so machines that look like small cash registers.

"This is where we amplify the human DNA. We put the human DNA on chips, and these machines here, you put the chip in this slot and close it up," Tanzi explains. "And the machine adds different liquids to the chip to process it, to actually look at the variants in the DNA and start elucidating the differences."

Using these gene chips, the machines sort through the genetic information from hundreds of families whose members have Alzheimer's Disease -- an important step in the process of determining what genes play a role in Alzheimers -- either advancing the disease or preventing it.

"And then you put it in, this is an oven, it's just a simple oven, and you put the chips in here and they turn around in this carousel and they bake," Tanzi continues.

The chips are then read by a computer that displays the individuals's particular genome -- all the genetic information that was passed down from their parents. Researchers compare the genomes of brothers, sisters and cousins to determine why, genetically, some family members got the Alzheimer's and others didn't.

"And this is the most beautiful research that you can do because you basically are getting new clues that are totally unpredictable, you are getting new genes and new proteins that are sending you in totally new biological pathways that you would have never thought of that could be involved with Alzheimer's," Tanzi said.

"This is the most beautiful research you can do because you basically are getting new clues that are totally unpredictable."

-- Dr. Richard Tanzi

Tanzi calls this search for new genes the Alzheimer's Genome Project. When he started in 2006, only four genes had been linked to Alzheimer's -- and Tanzi had co-discovered three of them.

Those first four genes led to significant understanding about how Alzheimer's works, and they also led to new drugs to help dampen its effects. Tanzi was confident there were other genes involved in Alzheimer's, each one a potential new drug target.

The problem was that finding them would cost millions. And such a risky and expensive project was unlikely to be funded by the federal government or even private foundations.

"I was thinking, how do I ever raise enough money to be able to scan the whole human genome? It was kind of frustrating because here you knew you were able to scan the whole human genome in an unbiased manner to find the rest of the Alzhimer's genes, and I knew that 70 of the recent genes remain missing, but it was going to cost millions, a couple million dollars to do the experiment, and then along came my white knights!" Tanzi said.

Tanzi met those 'white knights' about five years ago. They were representatives from three prominent Boston-linked families: The Rappaport family of Nantucket, the Morbys of Martha's Vineyard and the McCance Family of Boston. The group's founding families are mostly venture capitalists who made their fortunes identifying the world's great visionaries and then supporting them as they built some of the most transformative companies of the 20th century. Now, they're turning to address Alzheimer's, largely because they see it as the best way to use their earned fortunes to help humankind.

Together, they would form a group called the Cure Alzheimer's Fund and become Tanzi's biggest supporters and his primary funders. Tanzi told them about the cash-register-like DNA machines just coming on the market, and he talked about the recently completed Human Genome Project, a map of humankind's 25,000 to 35,000 genes. The families believed Tanzi when he said genes are the compass to finding a cure or a preventative for Alzheimer's.

Now, Tanzi has been looking for four years, and he's identified more than 100 additional genes implicated in the disease. He is painstakingly testing the most important ones for undeniable proof of their role.

"So amongst the ones we found, beyond the original four, we have one, called Adam 10, where we did the whole package with Cure Alzheimer's Fund support. We found the genetic information that implicated the gene, we found defects in the gene, and we have shown using animal models -- mouse models -- how these defects in this gene causes Alzheimer's disease. And now we can think about drug discovery," Tanzi said.

"I knew that 70 of the recent genes remain missing, and it was going to cost millions... then along came my white knights!"

-- Dr. Richard Tanzi

Before investing in Tanzi, the founding families asked him and other medical investigators to create a comprehensive research plan, or roadmap, that would lead to finding a drug that can stop the pathology of Alzheimer's at its earliest point.

Jeff Morby, founder and chairman of the Cure Alzheimer's Fund, says with Tanzi taking the lead, they've recruited a consortium of top-flight doctors, the best and brightest they could find from labs across the country, to do the work their plan requires.

"The roadmap defines the things we are going to fund in more or less priority fashion. So as we discover new insights into the science of Alzheimer's, we are constantly revising the roadmap," Morby said. "And this is part of the venture capital approach to venture philanthropy that we're talking about."

Dr. Anne Young, chief of neurology at Mass General Hospital, says the families behind Cure Alzheimer's Fund have enabled Tanzi and a host of hand-selected other doctors to take risks and chances with their research, supporting projects other funders likely would be reluctant to touch.

"Dr. Tanzi finished the entire screen of the genome for genes. And he's got a whole repertoire of genes, each one of which is a drug target for curing Alzheimer's," Young said. "And now it's simply a matter of working through those end models and testing whether you can interfere with it and change the disease. This is so different from what we had 10 years ago. It is a breakthrough to have that kind of approach."

Young, Tanzi and others point to the limited amount of federal dollars being put into Alzheimer's research as a real problem. Less than $500 million a year is granted to Alzheimer's investigators, compared to billions given to other diseases. Alzheimer's research is not science constrained, they say, it's budget constrained.

"I think we have a lot of really good avenues to take, they just have to be taken. We need the funds and we need to go there. It's like a roadmap is there. I always think of it as the Yellow Brick Road," Young said. "First you have to go through the field of poppies and the enchanted forest."

Now, Young said, the researchers know where they're going. "It's no longer like 20 years ago when we didn't know what we were grasping at. We have genes now. We have drug targets."

"It's important to understand we can move fast, and we pick the best researchers."

-- Jeff Morby

The group isn't just doing genetics. It funds a variety of experiments looking for ways to detect symptoms early; and even methods of administering the drugs they expect will be developed from the information they gather. For example, one of their doctors has found a way to monitor a single neuron in the brain of a mouse to see what impact a medication will have on the functioning of that neuron, allowing scientists to test potential medications.

Another study, Morby says, involves going through the brains of dead Alzheimer's patients and finding where the damage has taken place and then correlating it with the genomic information.

"This person has damage to the hypocampus and he has this kind of gene, we can say, okay, this kind of gene and this damage are related," Morby said.

In addition to raising private donations via their website, as well as attracting some federal research dollars, the now-four founding families have spent more than $10 million of their own fortunes on research. $10 million in five years may not sound like a lot of money for such successful families -- but that's by design, says Henry McCance, another founding family member and the Chairman Emeritus of Greylock Partners, one of the nation's premier venture capital firms. McCance says one of the tactics venture capitalists use is to invest slowly.

"(At) Greylock when we do a startup project, we put enough money in to get to an important milestone or development, and then we reassess the project," McCance said. "And if the momentum is good and if the opportunity looks as sound as we originally expected and the management team has grown, and all sorts of other factors, than we will, if you pardon the phrase, we will double down on our investment. We'll enthusiastically put more money behind."

Even with McCance ready to reinvest, the problem Cure Alzheimer's Fund faces is the approximately $3 million a year the founders are putting into the organization is not enough to cover everything they think needs to be done to find a cure.

So they're contacting billionaires, and putting out calls to their colleagues, business competitors, other foundations and universities. It's time for a Man on the Moon project to stop Alzheimer's, they say, before the sheer numbers of demented people overwhelms the nation's healthcare system.

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