Obstacles by Dave Schubert, PhD


David Schubert, PhD, Professor
Salk Institute for Biological Studies
La Jolla, CA  92037 schubert@salk.edu

May 28, 2013


Those of us fortunate enough to make it to 80 will have a 50% chance of suffering from Alzheimer's disease or another form of dementia before we die. And there is currently no known way to reduce the odds or slow the mental deterioration. These grim facts are already a reality to the 5 million Americans living with the disease.

It is projected that by 2050, unless breakthroughs are made, 14 million Americans will have dementia, at an annual cost of $1.2 trillion. Finding effective treatment or prevention of Alzheimer's would help avert a huge and costly healthcare disaster. Yet during the last few years, there has been very little funding available for developing dementia drugs or conducting the required clinical trials.

To date, clinical trials by pharmaceutical companies for drugs to treat dementia have been disappointing. Because of these repeated setbacks and the predicted risks of further failures, many pharmaceutical companies are dramatically cutting back or eliminating their research efforts in these areas. There are multiple reasons for the poor clinical trial results, including the complexity of the disease and a dogmatic focus by the pharmaceutical companies on a disease pathway that, in my opinion, is unlikely to be relevant for most patients. They have tended to focus on technologies that have worked for less complex diseases but haven't proved to be effective in neurodegenerative diseases.

Historically, most of the innovation in medical research has come from universities and research institutions supported by the National Institutes of Health. But the NIH hasn't stepped up to fund Alzheimer's research at the levels needed. Currently, only 1.6% of NIH funds are spent on research related to dementia, compared with 10% for AIDS, yet there are about five times as many Americans with dementia as withHIV, the virus that causes AIDS.That bleak funding picture isn't likely to improve without intervention, in part because, in the face of budget cuts, the peer-review system has grown increasingly conservative and less willing to support innovative research in areas such as Alzheimer's drug development, where the risks of failure are significant. Furthermore, once a promising lead drug candidate is identified, there is no way to know whether it works unless it is tested in human clinical trials. For Alzheimer's, this requires first conducting a series of toxicology tests (at a cost of about $1.5 million), followed by Phase I and Phase II testing (at about $25 million) and then the even more expensive Phase III trials.

During the last few decades, much of the cost associated with the initial two clinical trial steps has been funded by venture capitalists. If successful, the drug candidate is then sold to a pharmaceutical company, which conducts the Phase III trial. However, because of repeated clinical trial failures and the retreat of pharmaceutical companies, venture capitalists have become reluctant to risk funding innovative dementia drug development.

A final funding alternative for Alzheimer's drug research has been foundations and charitable organizations. But while these groups are of great help in supporting preclinical work, they typically do not have the funds required for clinical trials, and if they do, they tend to support the most conservative approaches.

At this point, it seems unlikely that conservative approaches will yield results, and it's clear that we need to innovate in developing new kinds of dementia drugs. Given the sorry state of funding for dementia research, innovative science will also require innovative funding.

Here's one outside-the-box idea for a new source of funds to support drug development. The federal government could set up an investment vehicle to support clinical trials of dementia drugs. It would not be without risk, and Americans would invest in part because they support research dollars going to such an endeavor. But if the funding ultimately produced an effective drug, the government could then offer returns based on the trillions it would save in healthcare costs for older Americans.

Another idea would be for universities and research institutions to solicit targeted, tax-deductible contributions that could be directed toward funding research on a specific promising drug candidate that is ready for clinical trials.

The existing ways of funding drug development for Alzheimer's and other age-associated dementia are not working, and it is in the interest of all of us to come up with better ideas. Irrespective of the mechanism, there must be a collective will of the American people to find a cure. Dementia is perhaps our greatest medical challenge, and the FDA is doing its part by making Alzheimer's disease clinical trials much more expedient. But we also need to solve the funding problem.

David Schubert is a dementia researcher and a professor at the Salk Institute for Biological Studies. He has received NIH funding in the past.

Copyright © 2013, Los Angeles Times



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