Storms and Science – Delegates Brave the Weather to attend our Novel Advances in Disease Modeling and Toxicology Event

Well it wasn’t a good start to the day – storms hit Boston the night before with power outages in the area. Trains were seriously affected resulting in more people driving into the city on the morning of the event which, in turn, meant parking was a problem. Despite these challenges, we still managed to host a successful workshop with many delegates braving the elements to attend the event.

The event, held on October 17th, 2019, was titled Novel Advances in Disease Modeling and Toxicology and was co-sponsored/co-chaired with Axion Biosystems. We had a great line-up of key opinion leaders from Novartis, Bristol-Myers Squibb, Fulcrum Therapeutics, Hussman Institute for Autism, University of Georgia, STEMCELL Technologies and Cyprotex. The venue of the Boston Marriott Cambridge was perfectly located close to the pharma and biotech hub at Kendall Square.

A key theme of many of the presentations was the use of human iPS cells, with many presenters describing the benefits of patient‑derived cells in their research. Neuronal, cardiac and hepatic research featured heavily in the agenda as well as the widespread application of multielectrode/microelectrode array (MEA). Several of the presentations focused specifically on disease modelling and how the latest technological advances can be applied to better understand disease and explore potential, innovative treatments.

Laszlo Urban from Novartis opened the session and provided an excellent overview on off-target secondary pharmacology effects and the concept of quantitative system pharmacology. This included a critical evaluation of the tools and procedures used for early safety assessment.  Several interesting case studies were presented which emphasised the critical role of (unbound) exposure in assessing specific safety margins for key targets.

John Graef from Fulcrum Therapeutics presented a fascinating insight into their Fragile X Syndrome (FXS) programme and how Fulcrum used patient-derived excitatory neurons in conjunction with MEA to model FXS in vitro. The talk further examined protein expression in FXS and WT neurons and determined levels required for correction of FXS phenotype.

Michael Nestor presented latest research from the Hussman Institute for Autism. The presentation provided details of an emergent hypothesis into the causes of autism in terms of an imbalance between excitatory and inhibitory neuronal activity. His research utilised patient and control human iPSC-derived 3D organoids and monitored network activity through MEA.

Lohitash Karumaiah from University of Georgia gave an interesting presentation on glioblastoma multiforme (GBM) which is an aggressive form of brain cancer with no effective treatment. The presentation focused on assessing the efficacy of CAR-T-cell therapy in inhibiting proliferation of patient glioma cells. Impedance measurements were used to monitor T-cell mediated cell lysis.

The remaining presentations focused on how novel technologies are being applied to improve the prediction of drug-induced toxicity.

Xiaoliang Zhuo from Bristol-Myers Squibb presented retrospective analysis of BMS-932481 – a clinical candidate which caused unexpected dose dependent drug induced liver injury (DILI) despite being well‑tolerated in preclinical species. Species differences in key hepatic drug transporter functions such as hepatic uptake and inhibition of BSEP and MRPs were postulated to contribute to these observations. In collaboration with DILIsym, a PBPK model was developed to predict dynamic hepatic exposure of the parent and its main human metabolites, and improve assessment of DILI risk.

Presentations from Hong Shi from Bristol-Myers Squibb and Vincenzo Macri from STEMCELL Technologies focused on the important topic of cardiotoxicity and the use of beating cultures of human iPSC-derived cardiomyocytes in combination with MEA to assess potential drug-induced cardiac risk.

Finally, Chris Strock from Cyprotex gave a review of the latest cell-based technologies and case studies for assessing organ-specific toxicity. Evaluation of iPS cells, a comparison 2D and 3D cell-based models and techniques such as electrophysiology and high content imaging were presented including their role and value in prediction of clinical drug‑induced adverse effects.

Knowledge sharing is a key focus of Cyprotex and forms part of our corporate social responsibility initiative. Our scientific events provide a platform for speakers to showcase their latest research and provide the audience with a forum to network and learn about cutting-edge science which may be relevant within their own teams and projects.

We would like to thank speakers and delegates for their contribution and participation in the event. Cyprotex are planning more scientific events in 2020.

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