Heading Back to the Lab to Crack Alzheimer’s Disease

August 10, 2017
By Josh Baxt, BioSpace.com Breaking News Staff

There are two Alzheimer’s disease trends that should be catching everyone’s attention. First, the number of cases continues to rise. And second, potential treatments continue to bomb out in clinical trials. To put it in economic terms, demand for therapies is ballooning. Supply, however…actually there is no supply.

This inability to develop effective therapeutics is deeply troubling. We are trying to build a seawall against the coming demographic tsunami and the mortar will not hold.

Here are some familiar statistics. According to the Alzheimer’s Association, there are more than five million Americans with Alzheimer’s. That number could rise to 16 million by 2050. Currently, dementia care costs $259 billion a year. By 2050, that already big number could balloon to $1.1 trillion. For context, the entire 2017 U.S. government budget is around $4.1 trillion.

Drug companies look at these numbers and see two things: a massive unmet medical need and the potential for equally massive profits. These twin motivations have launched multiple trials, but so far the results have been abysmal.

In November 2016, Lilly ’s anti-amyloid drug solanezumab failed a large trial. In February 2017, Merck ’s verubecestat suffered the same fate. Other high-profile trials have also gone down in flames. Nothing seems to work.

These results are disappointing on every possible level. Desperate patients and families, who believed help was on the way, have seen their hopes dashed. Scientists, physicians and many others, who spent years moving these ideas forward, have watched their work go down the drain.

But these failures outline an even more fundamental question: Do we even understand Alzheimer’s disease?

The therapeutic track record indicates that we don’t. Many of these failed drugs have targeted amyloid plaques, which are heavily deposited in Alzheimer’s brains and seemed like an appropriate target. Other research is focusing tau phosphorylation.

One intriguing possibility is that Alzheimer’s may be linked to glucose metabolism, so-called type 3 diabetes. If that’s the case, then the numbers cited above might be embarrassingly low, and the diabetes crisis is only the trailer for the upcoming dementia epidemic.

At present, we’re not sure if any of these factors are driving Alzheimer’s, either singly or together. On the surface, they all make sense but more work needs to be done.

The only way to make progress against Alzheimer’s is to make it a priority. Policymakers are fond of going to war against cancer, but dementia may be the greater threat. We need to identify better biomarkers to detect the disease early, develop more precise models and gain a better understanding of both causes and effects. In other words, we need to invest in basic research.

Complex diseases require many solutions. Combination chemotherapy helped us make great strides against cancer. The AIDS cocktail transformed a deadly disease into a chronic one. I suspect the same will be true with Alzheimer’s. But we have to identify the right targets and develop matching therapies. We have to do more, now.

Josh Baxt has been a science and healthcare writer for more than 18 years, working at Scripps Health and the Sanford-Burnham Medical Research Institute before going freelance in 2011. He writes about molecular biology, genomics, pharmaceuticals, emerging medical technologies, regulation and public policy. He is based in San Diego.