In this three-part webcast, Professor Henrik Zetterberg first provided an overview presentation on recent developments in biomarker-supported drug development for Alzheimer’s disease. Dr. Sebastian Illes then shared the results from a recent study where the effects of partial reduction of Aβ production on synaptic function in vitro was investigated. Finally, the webcast concluded with a panel discussion led by Dr. Paul Karila on how translational biomarkers and functional studies can be employed in early drug discovery programs.
Cerebral deposition of Aβ peptides, especially Aβ42, is considered the major neuropathological hallmark of Alzheimer’s disease (AD) and the putative cause of AD-related neurotoxicity. Aβ peptides are produced by sequential proteolytic processing of amyloid precursor protein (APP), with β-secretase (BACE) being the initiating enzyme. Therefore, BACE has been considered an attractive therapeutic target in AD research and several BACE inhibitors have been and are currently tested in clinical trials. But despite the massive efforts, to date, all have had negative outcomes or even led to worsening of cognitive function. AD can be triggered by Aβ years before the first symptoms appear and one reason for the failures could be that the clinical trials were initiated too late in the disease process. Another possible explanation could be that BACE inhibition alters physiological APP processing in a manner that impairs synaptic function, causing cognitive deterioration.
This presentation will highlight a study conducted in collaboration between the University of Gothenburg and Cellectricon AB where the effect of partial reduction of Aβ production on synaptic function in vitro was investigated since it is known that complete inhibition of BACE causes functional side effects. Further, biomarker-supported drug development will be discussed, in particular how biomarkers may be used to ensure the enrolment of the “right” patients with the pathology against which the drug is directed in order to detect drug effects on the disease process, and as safety biomarkers to detect adverse effects. The talk will include examples from concluded and ongoing clinical trials in the AD research field and suggestions on how the employment of a translational biomarker toolbox could speed up drug development from drug exposure in disease models to early phase studies in humans, and further towards conclusive late phase clinical trials with greater chances of success.
After the talk, Professor Zetterberg will discuss opportunities to implement new approaches for research and drug discovery programs for Neurodegenerative Diseases together with Paul Karila (CSO, Cellectricon AB) and Sebastian Illes (Director of CNS research, Cellectricon AB).
Henrik Zetterberg, MD, PhD
Professor of Neurochemistry and Chief Physician at the Institute of Neuroscience and Physiology, Sahlgrenska Academy at the University of Gothenburg & Professor of Neurochemistry at University College London
With a background in molecular biology and medicine, Dr. Zetterberg has spent the past 20 years focusing on the development of biomarkers for Alzheimer’s disease, Parkinson’s disease and other brain disorders. His research involves evaluation of biomarkers in cell and animal models, as well as in longitudinal studies of patients and healthy individuals. He has developed new diagnostic tests for Alzheimer’s disease, as well as new preclinical models, and has shown that amyloid pathology precedes tau pathology by around five years during the Alzheimer’s disease process in humans. In addition, that altered amyloid homeostasis in the brain is evident already in pre-symptomatic stages of the disease and that the diagnostic usefulness of Alzheimer’s biomarkers decreases with age due to increased prevalence of preclinical Alzheimer neuropathology.
Dr. Zetterberg has published more than 1300 scientific articles, is a Wallenberg Scholar, and has received the Erik K. Fernström prize for young scientists, the Inga Sandeborg prize for research on Alzheimer’s disease and the Parkinson Research Foundation Research Award.
Sebastian Illes, PhD
Director of CNS research at Cellectricon
Sebastian joined Cellectricon in 2018 as director for the company’s CNS research services. Prior to joining Cellectricon, he held a position at Gothenburg University, Sweden, where he and his team conducted research on neural development, neuroinflammation and neuronal circuit function. Previously, Sebastian was a Postdoctoral Fellow at the Institute for Molecular Regenerative Medicine (PMU, Salzburg, Austria) and a guest researcher at the Natural and Medical Science Institute, Reutlingen, Germany. He did his PhD at the neurology department at the Heinrich-Heine University, Duesseldorf, Germany.
Paul Karila, PhD
Chief Scientific Officer at Cellectricon
Paul joined the Cellectricon in 2012 as head of the company's Discovery Services. He previously worked at AstraZeneca (AZ) where he held leadership positions at the Departments of Molecular Pharmacology and Neuroscience. At AZ, Paul led teams responsible for target identification/target validation and ion channel and GPCR profiling in LI-LO phase, mainly on analgesia targets. Prior to joining AZ, Paul was a Postdoctoral Fellow at School of Medicine, University of Pittsburgh, USA, studying neurobiology using electrophysiological methods. He has a PhD in animal physiology from University of Gothenburg, Sweden.