Ensuring the 21st Century Cures Act ends Alzheimer's
© Greg Nash

“We are now one step closer to … unlocking cures for diseases like Alzheimer's,” President Barack ObamaBarack Hussein ObamaOur remote warfare counterterrorism strategy is more risk than reward Clinton lawyer's indictment reveals 'bag of tricks' Chelsea Manning tests positive for COVID-19 MORE said of the 21st Century Cures Act, which he signed into law this week. But to unlock a cure for Alzheimer’s disease, we first have to take steps to avoid recent failures like Eli Lilly's anti-amyloid Alzheimer's disease treatment, solanezumab, an all-to-common disappointment to the medical, scientific, and patient community who follow Alzheimer’s drug development.


In fact, decades of research and hundreds of billions of dollars spent in public and private money have not produced even one disease-modifying treatment for Alzheimer's. This is mostly due to the fact that the vast majority of this research is conducted using mice and primates—animals who do not get the disease naturally, but have been genetically modified to mimic the disease.

In most cases, scientists “engineer” one or several genetic risk factors in these animals, and then "fix" the artificially created disorder. However, these “fixes” have not translated to functional improvements in humans with Alzheimer’s.

Solanezumab targeted amyloid, a protein that is found in abnormally high concentration in the brains of Alzheimer's patients and creates a number of toxic effects. In June, another high-profile failure occurred in a clinical trial testing a drug meant to work against a different suspect protein, tau. As drug companies and researchers struggle to salvage failed studies, they are tempted by small percent improvements in subsets of participants. Even by tweaking doses and aiming at earlier stages of the disease, these changes do not made substantial improvements in outcomes.

So what should we do? The path forward is two-fold. First, we must help people prevent Alzheimer's. We have known for quite some time that factors such as diet, exposure to toxins (e.g., smoking), poverty, access to health care, education, social interactions, and sex differences all play major roles in aging and the development of Alzheimer's. Indeed, some of the most encouraging news about Alzheimer's and related dementias are the recent reports that rates have declined in the UK and in older adults in the United States. Given the failures in Alzheimer’s drug development, this decline is likely driven by management of risk factors.

More funding to study and share information about these factors is needed. Making them part of the foundational equation to preventing Alzheimer's is essential. Doing so will not only protect against Alzheimer's, but vastly improve quality of life for people in general.

Beyond prevention, we can also make headway on treatments for people who develop Alzheimer's disease. Congress and the Obama administration have invested unprecedented amounts—$350 million in 2016 alone—toward research, with a goal of finding effective interventions to treat or prevent Alzheimer's and related dementias by 2025. We must ensure these resources do not repeat past mistakes, but are used effectively by focusing on human-based research including modern clinical, epidemiological, computational, tissue-based and in vitro studies.

Moreover, testing on animals can also fail to detect significant safety issues with potential new Alzheimer's drugs. These concerns, which have included swelling and micro-bleeds in the brain, have only became apparent during clinical trials with the use of human neuroimaging techniques. In contrast, human-based in vitro techniques, such as human induced pluripotent stem cells derived from Alzheimer's patients, have been able to more accurately predict experimental drug response in humans than animal models. A shift to carefully monitored human studies and human-based laboratory approaches must become a priority for the field.

While other drugs are still in the pipeline, and we all hope for the best, should we expect success without making major changes? We must turn our focus on human biology and human patients, in order to improve care and delay or even prevent this devastating disease in our aging population now.

Ann Lam, Ph.D., is a medical research specialist at the Physicians Committee for Responsible Medicine, and Kristie Sullivan, M.P.H., is the vice president of toxicology with the Physicians Committee for Responsible Medicine.

The views expressed by authors are their own and not the views of The Hill.