Bill Gates’ Funding Boost for Dementia Research Misses an Opportunity

Microsoft founder Bill Gates recently announced a personal investment of $50 million in the Dementia Discovery Fund (DDF), a public-private fund supported by charities, industry, and government to diversify the search for a drug to treat dementia. Gates wants the scientific community to look beyond amyloid and tau proteins in the brain, two key hallmarks of the disease, for the causes of dementia with the ultimate goal of creating an effective treatment. He is correct that so narrowly focusing research into the role of these proteins has diverted our attention from more productive research. But his laser focus on treating rather than preventing dementia is not the only strategy to overcome this disease. The search for a drug to treat Alzheimer’s disease and related dementias has met with little success. And given the rapid rise in the incidence of these diseases, the scientific community and those who fund their work would better serve the public by shifting their focus to prevention—or, at the very least, making prevention a high priority.

We have some suggestions:

First, as we have learned in other major research pursuits, the use of animal models of disease typically fails to provide us with meaningful insights into how a disease originates and progresses in humans. Therefore, all research should take full advantage of the many innovative methods that are human relevant. We applaud DDF for its support of in vitro human-based approaches in their search for therapeutics. These include using cell-biology based approaches to find targets in human brain tissues (Cerevance), human neurons derived from induced pluripotent stem cells (Gen2), in vitro platforms to restore immune cell function (TIAKI therapeutics), and an in silico program to screen a library of more than 500,000 compounds virtually for drug candidates (DDF ChemCo).

Second, investments should be made in these underfunded areas:

• Human brain tissue banks and resources like the Allen Cell Types Database. To better understand the causes of dementia at the population level, we need more research into the lifestyle factors that play a critical role in driving the disease, which can help explain racial-ethnic disparities.
• A better clinical test to diagnose the disease earlier and track its progression. This will help identify patients for earlier intervention studies. If we had a disease specific biomarker like cholesterol for heart disease or hemoglobin A1C for diabetes, the development of Alzheimer’s may become easier to control. The key to finding such a biomarker will require a better understanding of the external factor(s) driving the disease in humans and strictly focusing the search in human specimens. More clinical trials assessing the efficacy of nonpharmacological interventions such as changing dietary habits, so that we can give people evidence-based advice to take control of their health.
• Design clinical trials to include patients with multiple chronic conditions so that interventions can be broadly applicable to patients with many chronic conditions. Many drug trials exclude these individuals in order to demonstrate the specificity of a treatment for the disease. However, Alzheimer’s often occurs with other chronic medical conditions. Testing lifestyle interventions would fill this research gap and encourage patients to participate in trials before they develop any signs of the disease.
• Use the common database for which Gates advocates to catalog links between modifiable lifestyle patterns and dementia prevalence or incidence over time in different parts of the world. Moving away from focusing on data derived from animal models and failed drug trials will help us better understand what is really driving dementia that we can change in a short period of time.

Despite billions of dollars spent, pharmaceutical companies have not been able to find a drug to even delay the onset or progression of dementia. Pfizer’s recent announcement to end its research program on developing new drugs for Alzheimer’s disease is indicative of how fruitless and disappointing these efforts have been (hyperlink to: https://www.usnews.com/news/top-news/articles/2018-01-07/pfizer-ends-research-for-new-alzheimers-parkinsons-drugs). With the high financial burden the disease implies and the devastating impact on the patient and families, we must invest more in human studies that will help us understand how to treat and prevent this disease. If Gates devoted a mere 10 percent of his $100 million planned investment in these areas, we might spare millions of people from the crippling effects of dementia.