After years of disappointing progress in Alzheimer’s Disease (AD) research, we are finally beginning to make breakthroughs that could have a real impact on AD patients, their families, and the healthcare industry at large.
Worldwide, nearly 44 million people now have AD or related dementia, making these conditions the top cause of disabilities in later life. The biopharma industry has invested billions of dollars into research to treat and prevent AD, yet this work has faced many obstacles, including difficulty identifying biomarkers, tracking the disease’s progress in the brain, and recruiting patients to trials while they are still asymptomatic. But in recent years we’ve begun to see breakthroughs that is driving our research in new directions. Many of these accomplishments were highlighted at the Alzheimer's Association International Conference in July, where excitement about recent accomplishments was palpable.
One of the most talked about topics in sessions and networking events was advances in understanding tau pathology and the ability to conduct tau imaging in live patients. This has opened up our ability to see how the tau pathology progresses, and to understand the interactions between tau and amyloid pathologies in living patients. Several sessions explored this topic, including a review of a Mayo Clinic study on predictors of regional tau-PET uptake, and another on the association between amyloid and tau accumulations in patients’ brains and its influence on clinical features.
Until very recently, tau imaging was impossible in vivo. With these new tools we will be able to gather new insights about how the disease progresses, which will steer us down new research paths and hopefully lead to breakthroughs in our understanding of this disease. There is a growing consensus in the research community that we need to address both tau and amyloid pathologies to effectively treat AD. These advances will help make that happen.
Recruiting through the GAP
Another topic of ongoing discussion at the event was the challenge of attracting AD patients to trials before they are diagnosed. Past research has shown that once a patient sees a neurologist about their symptoms, the disease is usually too far advanced for preventive treatments. Studies of healthy volunteers at risk of developing AD have shown the presence of amyloid beta sometimes decades before they become symptomatic, which means we have the potential to identify risk factors and develop treatments for patients well before they ever have symptoms – but only if we can recruit these patients to trials.
That is a significant hurdle to overcome. Traditional methods of recruiting, such as working with treating physicians, or reaching out to patient communities obviously won’t work.
In response, sites need to develop more innovative strategies for engaging and evaluating asymptomatic volunteers. Dr. Paul Aisen of the University of Southern California, San Diego explored this topic in his presentation on using run-in data for screen failure reduction, and the work being done with the Global Alzheimer Platform (GAP) to build large “trial-ready cohorts” for pre-clinical/prodromal AD trials. A key component of this project is to create a network of pre-qualified “trial-ready sites” with specific expertise in and uniform processes for the clinical and biomarker assessments required for prevention trials.
The GAP team, which includes academic, industry, advocacy and other Alzheimer’s leaders, have already designed a process of connecting feeder registries and studies to a GAP Registry to capture a variety of data on non-demented individuals interested in trials along with risk scores to support more efficient selection of candidates for in-person biomarker and clinical assessment.
There were also several sessions that reference data from the Dominantly Inherited Alzheimer Network (DIAN), an international observational study to understand a rare form of Alzheimer’s disease that is caused by a gene mutation, which is being funded by a multiple-year research grant from the National Institute on Aging. In one session, presenters discussed the value of investigating the rarer autosomal-dominantly inherited forms of AD to identify asymptomatic “at risk” individuals prior to the onset of cognitive decline.
Participants also discussed the need for more treatments to address the symptoms of AD, such as agitation, which plague many AD patients. Currently there are very few therapies to alleviate these symptoms leaving patients to use off-label drugs, which may not be as safe and effective as the industry would like. I was excited to hear about several phase 2 and phase 3 trials underway to develop such treatments.
Overall it was a phenomenal event that left me feeling optimistic about the future of AD research and the work being done by colleagues across the industry. We still have a long road ahead, but new breakthroughs are already giving us greater insight and will help guide us in pursuit of a cure.