Event info:

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.

The webcast is available for on demand viewing.

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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).