Alzheimer’s disease: Using deep human biology learning to guide next-generation treatments

The extensive journey of the history and progress of the amyloid hypothesis for Alzheimer’s disease (AD) has shown the importance of developing therapeutics based on precise mechanistic hypotheses informed by thorough analysis and understanding of the disease pathogenesis.

Human genetic advances over the last decade have identified dozens of genetic variants associated with AD phenotypes, many of which point towards immune-related mechanisms. While the details of how these mechanisms drive the pathophysiology of Alzheimer’s disease are not well understood, a variety of recently developed technology platforms are helping to address some of these outstanding scientific questions. In parallel, data science is revealing new questions as well as new hypotheses as advanced analytics are applied to deeply phenotyped human cohort studies in Alzheimer’s disease and other dementias.

This panel will discuss:

  • The importance of applying these learnings to identify promising drug targets
  • Emerging analytical methods to elucidate the pathogenic mechanisms for these targets by associating them with deep phenotypic data from human cohorts
  • Experimental techniques that can model complex human biology to enable understanding of new mechanisms
  • How these learnings can help guide biomarker identification and shape future clinical trials
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Janna Hutz

Janna Hutz

President, Eisai's G2D2 Center

Janna Hutz, Ph.D., is President of Eisai’s Center for Genetics Guided Dementia Discovery (G2D2) and Head of the Human Biology Integration Foundation within Eisai’s Deep Human Biology Learning R&D organization. In this role, Dr. Hutz oversees global efforts to incorporate learnings from human biology and data science to impact research decision-making across Eisai’s global oncology, neurology, and global health portfolio. She also serves as site head of G2D2, Eisai’s exploratory research center that seeks to deliver breakthrough solutions for Alzheimer’s disease and other dementias by leveraging human genetics, data sciences, and precision chemistry.

Prior to her appointment as President of G2D2, Dr. Hutz played an integral role in Eisai’s efforts to identify and validate genetically-supported targets for dementia, serving as the Head of Discovery Data Science at G2D2, where she established and led a task force that provides comprehensive data analysis tailored to all of Eisai’s discovery-stage neurology programs. In her previous roles, she also led G2D2’s IT, Informatics, and Translational Human Biology functions.

Before joining Eisai, Dr. Hutz worked in clinical research at Pfizer where she supported discovery and clinical programs in immune and inflammatory diseases by using human biology to inform target validation, indication selection, and precision medicine approaches for clinical programs. She began her career as a presidential postdoctoral fellow at the Novartis Institutes for Biomedical Research. Dr. Hutz holds a Ph.D. in Human Statistical Genetics from Washington University in St. Louis and a B.S. in Cellular and Molecular Biology from the University of Michigan.

Elena Dale

Elena Dale

Head of Pharmacology, Senior Director, Eisai’s Center for Genetics Guided Dementia Discovery (G2D2)

Elena Dale, Ph.D., is a Senior Director, Head of Pharmacology at Eisai’s Center for Genetics Guided Dementia Discovery (G2D2). In this role, she oversees preclinical projects and leads cross-functional teams supporting programs in Alzheimer’s disease and other dementias. Her key responsibilities include leading projects from target identification to candidate selection by combining human genetics data and preclinical research. Dr. Dale has an in-depth knowledge of neuroscience drug discovery and pharmacology, as well as extensive experience in leading internal research efforts and managing collaborations with academic institutions and contract research organizations.

Prior to joining Eisai in 2022, Dr. Dale worked at several other central nervous system (CNS) companies, including Wave Life Sciences, Novartis and Lundbeck. Her expertise in diverse CNS indications includes Alzheimer’s disease, depression, schizophrenia, Parkinson’s disease and epilepsy. She is the co-author on multiple peer-reviewed neuroscience publications, including 17 drug discovery studies and review articles. Dr. Dale received her Ph.D. in Neuroscience from New York University School of Medicine and completed her post-doctoral training at Columbia University Medical School.

Michael Nagle

Michael Nagle

Executive Director, Head of Human Genetics and Causal Biology, Eisai’s Center for Genetics Guided Dementia Discovery (G2D2)

Michael W. Nagle, Ph.D., serves as Executive Director, Head of Human Genetics and Causal Biology at the Eisai’s Center for Genetics Guided Dementia Discovery (G2D2). In this role, he creates the human genetics strategy for the company’s Deep Human Biology Learning (DHBL) R&D organization and leads a team of geneticists and informaticians who provide expertise and support to their Eisai colleagues.

Dr. Nagle’s key responsibilities include target identification and validation, biomarker discovery, and clinical trial patient stratification and design strategies. To implement the human genetics strategy and goals, he develops and assists in managing an internal infrastructure for computation and analysis, which identifies, internalizes, and analyzes key data for stakeholders throughout the organization.

Prior to joining Eisai in October 2020, Dr. Nagle held a series of positions at Pfizer, including Applied Genetics Manager, Principal Scientist in Computational Target Validation, and Senior Principal Scientist in the Internal Medicine Research Unit Integrative Biology Group. He supported early-stage discovery and target validation efforts through the integration of human and model system biological data. He also led the application of network-based and machine learning approaches to large genomic and other omics datasets to gain insight on pathways and networks influencing cardiovascular disease and heart failure towards identifying and validating novel therapeutic targets. In addition, Dr. Nagle led a small group of bioinformaticians in the application of various analytical approaches to internal and external datasets towards understanding pathways influencing cardiovascular and metabolic disease.

Dr. Nagle has had papers published across multiple therapeutic areas, including Cardiology, Early Alzheimer’s disease, Parkinson’s disease, Mental Health, Pulmonology, Type 2 Diabetes, and Neuroscience.

He earned both his Bachelor of Arts degree in Chemistry and Doctor of Philosophy degree in Molecular Medicine from Boston University, and later completed his Post-Doctoral Fellowship at the Boston University School of Medicine.

Carlos Cruchaga

Carlos Cruchaga

Professor, Washington University School of Medicine

Carlos Cruchaga, Ph.D., is a human genomicist with expertise in multiomics, informatics, and neurodegeneration. He completed his Ph.D. in Biochemistry and Molecular Biology in 2005 at University of Navarra in Spain. During his first post-doctoral, he conducted statistical human genetics studies focused on Alzheimer’s disease and Parkinson’s disease, completing his training in quantitative human genomics. Dr. Cruchaga established his laboratory at Washington University in 2011, studying the genetic architecture of neurodegenerative diseases. His interests are focused in using human genomic and other omic data (proteomic, metabolomics, lipidomics) to identify and understand the biological processes that lead to Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and other neurodegenerative processes. In 2019, he became the leader of the NeuroGenomics and Informatics group at Washington University.

Arsalan Arif

Arsalan Arif

Founder & Publisher, Endpoints News

Arsalan Arif is a news media entrepreneur who set out in 2015 to build his vision of an independent biotech news company at Endpoints News.