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science in mind

Key to curing Alzheimer’s may be changing drug development funding

MIT economist calls for Alzheimer’s ‘megafund’

Based on the current rates of success in creating new drugs for Alzheimer’s disease, it could take 260 years until the next one is approved, according to an analysis led by a Massachusetts Institute of Technology economist.

That depressing prediction, published in the journal Science Translational Medicine on Wednesday, is based on a model that presumes the current strategy for drug development continues. That consists largely of developing and testing drugs, one by one, that act on one particular target, the build up of beta-amyloid protein in the brain.

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“The more I dug into this, the more I was shocked to learn the numbers I assumed were reasonable for drug discovery are pretty different for Alzheimer’s,” said Andrew W. Lo, a professor of finance at the MIT Sloan School of Management. “The time it takes to investigate a particular compound is much longer, you have to do neurological testing, and the probability of success is lower — to the point where it turns out the number of new drugs for Alzheimer’s over the last decade is zero.”

Lo and colleagues from the pharmaceutical company Genentech and the University of California, Santa Barbara, propose a bold change in strategy given the dire need: 5 million Americans suffer from Alzheimer’s today, and disease-related Medicaid and Medicare expenses are projected to be $150 billion this year.

Instead of pursuing drug development in a largely sequential fashion, often focused on the exact same pathway, why not try a portfolio approach in which many targets are pursued simultaneously? Lo and colleagues argue that such a portfolio approach would broaden the net and increase the odds of finding a drug that can really treat the disease, not just the symptoms.

Such an endeavor would require a big investment: the researchers assembled a portfolio of 64 possible projects, each targeting a different biological mechanism. Pursuing that would cost $38.4 billion, the researchers estimated. The financial return would be a loss, and the probability that none would result in an approved drug was real: 13 percent.

Because of those risks, they suggested that a “megafund” fueled with private and public money would be the right way to underwrite such research, largely because of the savings that government health systems and taxpayers would reap if Alzheimer’s drugs were effective.

“We’re hoping to get governments to realize it makes a lot of sense for them to get actively engaged in thinking about how to raise this amount of money,’’ Lo said. “In fact, I would argue it’s trivial compared to the impact this is going to have on government budgets in the long run,” as the population ages.

To Lo, recent successes in cancer drug development are the benefits reaped from President Nixon’s 1971 “war on cancer,” when investment in the research went up substantially. Before the war on cancer, the budget of the National Cancer Institute was $270 million. By 1978, it was more than $770 million.

Similar progress in Alzheimer’s, he argues, will only be possible if the investment in research and development is also scaled up significantly — soon.

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.
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