By Associate Image Scientist Bianca De Blasi

Today I am going to summaries a number of interesting talks we have attended on Day3 of the AAIC virtual conference.

This third day saw an interesting session about repurposing Drugs Targeting Inflammation in which Malu Tansey (Univ Florida) explored drug effect targeting TNF on animal models to control inflammation while Knut Biber (University of Freiburg) explored the role of microglial cells In AD . The latter is a phenomenon that can be probed effectively with free water fraction by diffusion MRI, which is a topic of high interest at ixico and on which we are actively working on.

It is important to also mention the effort of Lewy Body Consortium reported by James Leverenz (Cleveland Clinic) aimed at exploring the complexities of DLB in a multi-centre study. In particular, they reported preliminary interesting relations to amyloid found in low amounts, coherently with using DaT SPECT for striatal assessment. This topic is of high interest for quantitative application.

We also enjoyed Linda Van Eldik's talk (University of Kentucky) on the role of inflammatory mechanisms in Alzheimer's. This talk focused on recent work developing more specific compounds for tackling maladaptive immune responses. Linda's work is still at the preclinical stage, but this talk highlights increasing interest in the role of inflammation in AD and AD treatments. Here at IXICO we are developing an image analysis pipeline for measuring inflammatory processes non-invasively with MR.

In addition to discussing the investigation of these new compounds, we could also appreciated how some studies have been disrupted by the covid19 pandemic which is affecting 80% of CNS clinical trials in AD. To this end, Hugo Geerts from Certara-SimCyp proposed the concept of virtual patients. Using Physiology-Based Pharmacokinetic Modelling and Quantitative Systems Pharmacology Modelling, they develop the concept of virtual patient correction for missing data to predict the clinical outcome under the original protocol. This method was validated on fragmented and trail unique dataset, appropriate for the specific patient population and therapeutic intervention. it accounts for individual patient characteristics and protocol amendment; it can account for medication changes and therefore allows the sponsor to use their original statistical analysis plan.

Finally, we also enjoyed the talks at the plenary sessions, focussing on clinical manifestation of AD. Constantino Iadecola (Weill Cornell Medicine) highlighted the role of vascular dysfunction in AD and its relation to cognitive impairment. On the other hand, Nick Fox (UCL) discussed the early-onset form of Alzheimer's disease. This talk provided a great high-level overview of the key phenotypic and anatomical differences between the early and late onset variants of the condition- an important consideration for trial design, and perhaps more relevantly for IXICO, for AI-based disease modelling experiments. Professor Fox also shared some quite moving videos of people with early onset AD, demonstrating the extent of their impairment. As a company that works solely with image data, this was a important reminder of the types of disease that we are working to tackle.

Thank you very much for listening and stay tuned for the summary for Day 4 at AAIC.

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