Pre-clinical study

The Institute of Science and Technology Austria (ISTA) in Klosterneuburg on the outskirts of Vienna is a PhD-granting research institute. Opened in 2009, the institute focuses on basic research in the natural sciences, mathematics and computer science.

ISTA employs professors according to a tenure-track model as well as postdocs and PhD students in an international graduate school. In addition to its commitment to curiosity-driven basic research, the institute holds the rights to resulting discoveries and promotes their exploitation.

Country and location: Klosterneuburg, Austria. Organisation type: Research Institute. Website: ista.ac.at.

Neurolentech GmbH

Neurodevelopmental disorders are a major unmet medical need with a high burden for patients and society. Neurolentech's vision is to become a world-leading company for patient-specific, molecularly defined cellular models in preclinical drug development for autism, epilepsy and intellectual disability.

Country and location: Klosterneuburg, Austria. Organisation type: SME - Small Medium Enterprise. Website: neurolentech.com.

Main contact person: Carsten Pfeffer, CSO, cpfeffer@neurolentech.com.

ISTA is the leader of Work Package 3. This work package creates human neuronal cell models from patient-derived induced pluripotent stem cells (iPSCs) obtained from participants in the L-serine clinical trial, together with matched control lines such as isogenic controls or family-member controls.

These 2D and 3D neuronal co-cultures are used to study how L-serine affects neuronal development, plasticity and sensitivity to seizure-like events under controlled laboratory conditions.

Neuronal activity and network function are monitored over time using advanced multi-electrode array technology, complemented by whole-transcriptome RNA sequencing to capture molecular changes.

The models also enable systematic drug-screening studies to evaluate whether L-serine shows synergistic or antagonistic interactions with commonly used anti-seizure or psychoactive medications, generating patient-specific functional and molecular data.

Overall, this work package allows direct comparison between in-vitro neuronal responses and the clinical outcomes of the same patients, including combination treatment effects.

Gaia Novarino is the principal investigator for the pre-clinical component of TAP-GRIN.

Role in the project: Principal Investigator.

She obtained her PhD in Developmental Biology from Sapienza University of Rome and worked at the Max Delbruck Center for Molecular Medicine in Berlin and at the University of California San Diego before joining ISTA in 2014.

Gaia Novarino is now Full Professor at ISTA, ERC grant holder, Simons Foundation Investigator, recipient of the Boehringer Ingelheim FENS Research Award, and Executive Vice President and Vice President for Science Education at ISTA.