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

Posted June 17, 2010

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.