The Alzheimer’s Drug Discovery Foundation (ADDF) hosted its 22nd International Conference on Alzheimer’s Drug Discovery on October 4-5, 2021. The virtual conference showcased the latest results from scientists worldwide, many of whom are supported by the ADDF, as well as innovative approaches to clinical trials and the critical importance of biomarkers. Over 1,000 registrants gathered from all over the world to share insights, present discoveries, and foster connections in Alzheimer’s research.
“The 22nd International Conference on Alzheimer’s Drug Discovery exemplified the progress we’ve seen in the field over the past year, much of which has been driven by the ADDF,” said Howard Fillit, M.D., Founding Executive Director and Chief Science Officer of the ADDF. “We have seen several advances in recent months, hitting crucial milestones in advanced biomarker development and drug targets. We are proud of our investments and partnerships that make these discoveries possible, and this conference shows that we are moving into the next era of drug discovery.”
Two main points of focus permeated this year’s conference: how to design better, more inclusive clinical trials and the importance of developing biomarkers that can improve diagnosis and track drug target engagement.
Designing better clinical trials
Multiple presentations advocated for the development of better clinical trials. In his keynote address, Jeffrey Cummings, M.D., Director Emeritus of Cleveland Clinic Lou Ruvo Center for Brain Health, Director of the Center for Neurodegeneration and Translational Neuroscience and Research Professor at the University of Nevada, Las Vegas department of Brain Health, discussed recommendations for exploratory trials in dementia. Dr. Cummings emphasized the need for the development of target engagement biomarkers, which are used to ensure drugs are working the way they were designed to work, and a wider array of blood-based biomarkers. “These are going to be transformative in terms of diagnosis, management and clinical trials,” said Dr. Cummings.
The keynote was based on findings from an expert advisory panel convened by the ADDF and The Association for Frontotemporal Degeneration providing guidance on best practices for the design of early drug trials for Alzheimer’s disease, frontotemporal degeneration (FTD), and other neurodegenerative dementias. Their guidance was published earlier this year in Neurology®, the medical journal of the American Academy of Neurology.
By creating more efficiencies in clinical trials (specifically phase 2a trials), hitting the right targets, and focusing on the right biomarkers, researchers and scientists can accelerate clinical research and discoveries, helping achieve proof of concept more rapidly and at a lower cost.
Identifying key targets
Several sessions highlighted the need to diversify targets to develop novel and effective disease-modifying drugs to treat, delay, or prevent Alzheimer’s and other age-related neurodegenerative diseases. While much research in the past focused solely on amyloid plaques in the brain, recent years have seen a growing interest in novel targets.
The ADDF believes the ultimate solution to treating Alzheimer’s will likely lie in a combination therapy approach, with drugs aimed at a wide array of the age-related biological changes that contribute to this complex disease. Presentations at the conference featured research on several of these novel targets, including Dr. Miranda Orr’s study of senolytics and Dr. Ihab Hajjar’s research on repurposing candesartan (an approved blood pressure medication), both of which are funded by the ADDF, and Dr. Gail Chan’s work to develop drugs harnessing exercise-induced signaling pathways. In a presentation given by Ottavio Arancio, MD, PhD, he discussed the potential that MW150, an isoform selective inhibitor of p38alphaMAPK, has on neuroinflammation and synaptic function. MW150 has shown to be effective in various mouse models and is currently in phase 2 clinical trial planning.
The importance of biomarkers
A critical component of treating Alzheimer’s disease is identifying specific biomarkers that can be used to make accurate diagnoses, identify the right patients for clinical trials, and monitor response to drug treatment. Blood biomarkers, eye scans, and digital technologies all show very promising results in paving the way forward.
In his keynote presentation, Kevin Yarasheski, PhD, senior vice president of C2N Diagnostics, presented on the clinical validation for Plasma Aβ42/Aβ40 as a biomarker for Alzheimer’s disease pathology. Preliminary data show that blood biomarkers such as C2N’s PrecivityAD™ test, which came to clinic in 2020, may have diagnostic, prognostic and therapeutic capabilities, leading to significant cost savings. According to Dr. Yarasheski, it should help identify and diagnose patients earlier and faster. “The [PrecivityAD] test is highly robust and precise—it is much more cost-effective and will help improve enrollment times for clinical trials and help get drugs approved faster.”
In a session on advances in fluid biomarkers, Russell Lebovitz, M.D., Ph.D., CEO and Co-Founder of Amprion, discussed his company’s work in detecting misfolded alpha-synuclein protein in spinal fluid as a diagnostic and prognostic marker for dementia. Amprion’s new test, SYNTap™, recently announced commercial rollout.
The test amplifies and detects this protein from just a few drops of spinal fluid. Alpha-synuclein builds up in the brains of people with Parkinson’s disease and Lewy Body dementia and is also found in some patients with Alzheimer’s. Amprion’s new test is highly sensitive and specific, meaning it is very valuable as a diagnostic tool. In clinical tests, it was more accurate than clinical diagnosis or imaging tests alone, and its predictive value was comparable to what researchers found in post-mortem examination of patient brains.
Inclusion in clinical trials
Despite a higher risk for Alzheimer’s and related dementias, Black and Latino Americans are underrepresented in federally and industry-funded research. Racial diversity in clinical trials is critical in advancing health equity.
The conference’s last session, moderated by Jason Resendez of UsAgainstAlzheimer’s Center for Brain Health Equity, highlighted the need to overcome these challenges, demonstrating that the lack of representation of underserved and underrepresented communities in brain health research is an urgent issue for researchers, policymakers, health providers, and patient advocates.
During their presentation, they shared concrete strategies for driving research equity in neuroscience research. For example, funding organizations have a role to play in making funds available for the extra costs associated with working in these communities. Researchers need to do frequent outreach within these communities, develop relationships, and address their concerns.
Fostering connections in research
Not only was the ADDF conference a forum for sharing groundbreaking Alzheimer’s data; it was also an opportunity for young scientists to foster connections in the research community. A hallmark of the ADDF’s approach is our high level of engagement and long-term commitment to our funded investigators and all those we believe have promising ideas to advance Alzheimer’s research.
Our conference encouraged these connections through the Startup Forum, which invites start-up companies, fellow entrepreneurs, VCs, and researchers working on drug development for dementia to be considered for brief presentations and a Q&A during the conference.
“Every year, we make incredible progress in accelerating the development of new drugs for Alzheimer’s disease and forging invaluable connections,” added Dr. Fillit. “This would not be possible without our rigorous and efficient research, exploratory trials, and pivotal partnerships.”