Cure Alzheimer's Fund: Targeting Breakthrough Research

Real progress IS being made

Written by Tim Armour Friday, 18 June 2010 14:57

In Response to Nicholas Wade’s NYT column, June 12, 2010:
“A Decade Later, Genetic Map Yields Few New Clues”
But real progress IS being made.

The promised breakthroughs and cures from the Human Genome Project may have been too optimistic from a timing perspective. But Wade may be too pessimistic when he writes, “Indeed, after ten years of effort, geneticists are almost back to square one in knowing where to look.”

Not really. As others in the piece say, the Human Genome Project and the HapMap project growing out of it have been essential to a better understanding of the genetic underpinning of many common diseases.  The evidence is clearly with Eric Lander who says in the article, “Having a common scaffold on which one can put all the information has dramatically accelerated progress.”

But why no cures yet? Because in plotting the genetic map, we learn that each step taken teaches us more as well as opens more questions to be resolved. For example, researchers have found that what was commonly regarded as “junk” between pieces of DNA isn’t “junk” at all; it has functions that contribute to biological processes just as the DNA does. And one of the bigger surprises has been that knowing the common genetic variants isn’t enough to find the causes of disease. Researchers must track down the rare variants or mutations with strong biological effects on the disease.  As Wade writes, “It now seems more likely that each common disease is mostly caused by large numbers of rare variants, ones too rare to have been cataloged by the HapMap.”

Yes; this is a very important finding, and one that would have been years ahead of us without the Human Genome Project and HapMap.  And this positions us well to take the next steps to reduce the time for development of effective therapies. Rudolph Tanzi, PhD, head of the Genetics and Aging Unit at Mass General Hospital and primary investigator of the Alzheimer’s Genome Project funded exclusively by Cure Alzheimer’s Fund, says: “Having identified over 200 new Alzheimer’s candidate genes through the Alzheimer’s Genome Project, we can now find the ‘causal’ DNA variants in Alzheimer’s, then determine which biochemical pathways are broken as a result, and discover therapies to “fix what is broken” based on that information.”

Another recent article in the Wall Street Journal reports that “Drug Makers Will Share Data for Failed Alzheimer’s Trials” (WSJ, June 11, 2010). Why so many failures? One major reason is that many of these drugs were developed without the knowledge of these genetic processes and their biological effects.

Yes, it takes time --- and much more money than has so far been dedicated to Alzheimer’s research --- to discover what genetics has to teach us about the basic causes of disease. But without following that trail, the cost and the failure rate will be much, much higher.

Sharing Data is Good But We Need to Better Understand Causes of the Disease

Written by Tim Armour Thursday, 17 June 2010 13:50

The Wall Street Journal, Reuters, and other publications carried an important story on June 11 indicating that “drug makers will share data from failed Alzheimer’s trials” to try to determine “what is wrong with the studies and what can be done to improve drug development.” (WSJ, Drug Makers Will Share Data From Failed Alzheimer’s Trials, June 11, 2010).

The short answer was given in that article by Ray Woosley, MD, chief executive of the Critical Path Institute: “We really believe drugs are failing because we honestly do not understand the disease.” YES! That is the truth. How can you make effective therapies when you don’t understand what causes the disease in the first place?

While pooling data and sharing resources is certainly a useful idea, an even more effective strategy would be to spend more time and money to understand the causes of the disease. Cure Alzheimer’s Fund is committed to the simple proposition that understanding the disease’s cause is the fastest path to a cure. And for Alzheimer’s, the story clearly begins with the genes. When Cure Alzheimer’s Fund was incorporated in late 2004 only four genes had been conclusively shown to modulate Alzheimer's progression. In addition, the association of three of the four genes was restricted to early onset Alzheimer’s, which accounts for fewer than 5 percent of Alzheimer’s disease patients. The fourth gene was associated with the much more prevalent late onset form of Alzheimer’s. However, this fourth gene accounted for less than 30 percent of the genetic component of late onset Alzheimer's. For more than 95 percent of Alzheimer's cases, the bulk of the contributing genetic factors remained unknown.

In 2005, Cure Alzheimer’s Fund committed to finding the remaining Alzheimer’s –associated genes, and to investigating promising novel therapies based on information learned from the first four genes. To this end, Cure Alzheimer’s Fund established and committed $4 million over 4 years to a new initiative named the Alzheimer’s Genome Project. Aided by the advent of the human genome map, the availability of new technology for gene identification and sequencing, and our researchers’ pioneering use of advanced statistical analysis we achieved what we believe is a great leap forward in the hunt for Alzheimer's causing genes. The Alzheimer’s Genome Project has identified over 200 new candidate genes in the first four-year phase.

Having the right set of targets as identified by careful and comprehensive genetic studies dramatically decreases the development time to a cure. For example, building from genetic research, investigators supported by Cure Alzheimer’s Fund have identified how aggregates of the “bad guy” Alzheimer’s protein, Abeta42, aggregate to create a hyper-toxic environment for neural synapses in the brain and how compounds originally designed to lower cholesterol may be effective in lowering Abeta42 in the brain. Most remarkably, recent research by Cure Alzheimer’s Fund supported scientists has demonstrated that the same Abeta42 that has been seen as the arch-villain in the Alzheimer’s play may in fact be part of the innate immune system of the brain, and therefore a “hero” gone bad under certain circumstances! This is paradigm-changing research.

All of which is to say that spending billions on drug development when the target of the drugs is still poorly understood is bound to result in, at a minimum, disappointment. See our article on “Why the Drugs Don’t Work” in the Cure Alzheimer’s Fund Quarterly Report for Q1, 2010 for specific information about why certain drugs have failed and what research is proving more fruitful.

In the meantime, pooling data from failed trials is certainly useful, but an even more efficient and effective strategy would be to put more attention, effort and money into understanding the basic causes of the disease.

New Report is Old News: Cure Alzheimer’s Fund has the Strategy and Roadmap to a Cure

Friday, 21 May 2010 05:25

Over the course of the last 5 years, all of us here at Cure Alzheimer’s Fund have been saying the same thing – Alzheimer’s is a national disaster, an encroaching tsunami that has the potential to bankrupt our entire health care system.

And, if you’ve been following the news this week, you’ve likely seen the recent Alzheimer’s Association report portraying this very same message.

Yes, we all agree – Alzheimer’s disease is a national imperative. In fact, a YEAR ago, we released our plan for a national strategy to end Alzheimer’s disease. As no other group has done, we called for a 10 year funding strategy of $5 billion per year and laid out a roadmap for exactly how that money should be spent -- because it’s not simply a fundraising battle. It’s just as important to know how to spend the resources most efficiently to find a cure. See our National Strategic Plan on our website at www.curealzfund.org.

$5 billion per year for research? In these economic times? YES.

As the just-released report says, within the next 10 years, the US government will spend $20 trillion on care for Alzheimer’s through Medicare and Medicaid.  That’s roughly 400 times what we spend on the research that will one day find the cure to this devastating disease. Until we re-balance that equation, we will NEVER change the trajectory of Alzheimer’s disease.

If we spend $5 billion per year for 10 years, that still doesn’t even come close to the ever-increasing cost of paying for the consequences of the disease. $50 billion vs. $20 Trillion. Which would you rather spend?

Of course we have to care for people with the disease; but we also have to dramatically increase the money we spend on research AND target that money strategically for the fastest way to a cure.  More money is one key; but more clear thinking about how to spend the money is the other imperative.

Cure Alzheimer’s Fund has a plan. So far, by following our roadmap, we have supported research that has identified over 100 genes associated with Alzheimer’s disease, a project the government has been working on for years. Cure Alzheimer’s Fund support has also helped validate the “oligomer” theory of Alzheimer’s pathology that shows that clumps of the Abeta peptide (oligomers) are the toxic entity that damages the synapses within the brain, not the well-known plaques.

And just recently, Cure Alzheimer’s Fund supported research has proposed a whole new paradigm for understanding Alzheimer’s pathology by pointing to the Abeta peptide, once believed to be only “junk” involved in causing Alzheimer’s disease, as actually part of the innate immune system!

Targeted research, well supported by public and private sources, is the only way we will “change the trajectory” of Alzheimer’s disease.

Thank you to those who have joined with us to support this kind of groundbreaking research, and welcome to those who join us now. Now is the time!

$21,500 Raised from Inaugural Running 4 Answers

Thursday, 13 May 2010 12:09

WOW. If we could only use one word to describe the inaugural Running 4 Answers, "WOW" would have to be it.

An event that sounded like a good idea 10 months ago, turned into a very windy, but perfect morning that welcomed almost 300 runners, walkers, spectators and volunteers and raised almost $21,500 for Cure Alzheimer's Fund. Not bad for a first try!

The list of people we have to thank is long. First on that list are the people of Cure Alzheimer's Fund who provided us with tremendous support:  Katie Cutler, Mariah Baril-Dore, Laurel Lyle and of course, Tim Armour.

Special thanks need to go to our technical/artistic support, Chris Gieger of Gieger Visual Communications (www.gieger.com) and printer, John Moss of Galvanic Printing (www.galvanicprinting.com). These gentlemen donated ALL of their work to Running 4 Answers – graphic design, website, posters, flyers and brochures. The cost of this alone would have been a huge hit to our little race &nash; we are so grateful! Without the support of our families and friends, up to and including race day, we never would have had such success.

Running 4 Answers progressed from a vague concept that at times seemed impossible to an event that was not only a great race, but also raised awareness of Alzheimer’s disease.

We are already developing ideas to make Running 4 Answers 2011 bigger and better than this year. Our plans include becoming our own non-profit organization, investing some money in advertising, working with other races to get the word out, and finding sponsors that make sense for our cause...i.e., hospitals, assisted living facilities.

On a personal note, this race altered a situation that has been hell from the beginning and made it something constructive. Something that gave meaning to the pain that my family and I have felt over the past ten years. It did not change my mom's situation or cure the disease, but it’s a step in the right direction.

We will be posting updates on our website as we have them.

Thank you again for your dedication and enthusiasm, and please continue to support Cure Alzheimer’s Fund and Running 4 Answers!

-Carolyn & Barbara