Als-on-a-chip · A tissue-on-a-chip platform for systems-level studies of ALS pathology and drug screening
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2015-09-30 → 2017-09-29
- EU contribution
- €164,653
- Participants
- 1
- Scheme
- MSCA-IF-EF-RI
Lines connect the coordinator with its partners.
Results in brief
A tissue-on-a-chip platform for systems-level studies of ALS pathology and drug screening
Amyotrophic Lateral Sclerosis (ALS) is a complex disease, characterized by diverse pathology that causes progressive motor neuron death. Unfortunately, most ALS patients die within 5 years. The single FDA-approved ALS drug (riluzole) has modest effects, so there is urgent need for new treatments to save patient lives. Currently, the main tool for preclinical ALS studies is mice overexpressing human SOD1G93A. However, despite promising results in this mouse model, more than 30 candidate ALS drugs failed to show efficacy in clinical trials over the past 20 years. These failures have been partly attributed to poor knowledge of ALS origins and pathology, key differences in the physiology of human and mice nerve cells, and the complexity of ALS pathology that cannot be blocked by “magic bullets”. The objective of the ALS-on-a-chip project was to develop a novel tissue-on-a-chip platform for systems-level studies of ALS pathology and drug screening. The proposed platform combines a novel cell-scaffold in vitro system with high-throughput quantification in order to quantify the effects of candidate ALS drugs on appropriate mouse and human cellular models of ALS. The proposed technology enables quantification of large arrays of 3D tissue analogs by modern quantification methods, providing novel ways describe ALS pathology and quantify drug effects based on advanced 3D models of the central nervous system (CNS). The project provided novel in vitro tools than could accelerate the development of new ALS treatments by improving the preclinical evaluation of candidate drugs in appropriate in vitro models. The proposed platform could be easily expanded/adapted in order to develop various kinds of physiologically-relevant models for central nervous system (CNS) physiology and pathology.
Data: CORDIS, © European Union
Project objective
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, which affects approximately 2 per 100000 people. Currently, there is no ALS treatment. The main tool for preclinical ALS studies is the hSOD1G93A mouse. However, despite promising results in this model, all candidate drugs failed in clinical trials. These failures have been partly attributed to differences in the physiology of human and mice nerve cells, and the inability of the established drug design approach to block ALS pathology. There is urgent need for new tools that will complement this mouse model, improve understanding of ALS pathology, and suggest better leads for clinical trials.The objective of the proposed study is to develop a tissue-on-a-chip platform for systems-level studies of ALS pathology and drug screening. The system is built around a novel thin porous scaffold, where systems of normal or ALS-type mouse and human motor neurons will be cultured inside an appropriate 3D ECM analog, and their response (intracellular signaling, cell processes, cell-cell communication) to stimuli panels in the presence of drugs will be quantified via high-throughput proteomics and fluorescent imaging. Acquired data will be interpreted by modifications of state-of-the-art system biology tools.The outcomes of the proposed research can lead to new ALS treatments by identifying new drug targets (via mechanistic description of ALS pathology), and by developing better ways to evaluate candidate drugs before clinical trials (via comparing drug response in human and mouse cells). Results can be translated to other neurodegenerative diseases. Finally, the proposal offers an opportunity to a promising researcher to relocate from MIT to Greece, collaborate with a leading neurobiology lab in a world-class environment and a systems pharmacology SME, and translate his research via two startup companies. The host envisions the opportunity for a tenure-track faculty position for the experienced researcher.
Original text from CORDIS.
Participants
- IDRYMA TECHNOLOGIAS KAI EREVNAS · IRAKLEIOCoordinatorGreece
Links
- View on CORDIS
- DOI: 10.3030/658850
- http://www.imbb.forth.gr/en/about-imbb/communicate-with-imbb-2/personel-directory-2/item/2416-tzeranis-dimitrios
Data: CORDIS, © European Union