Acetylcholinesterase Inhibitors as Potential Anti-Alzheimer Drugs: Prooxidative and Cytogenotoxic Properties (SafeAChE)

Project code: 337-00-205/2019-09/19
Project type: Project of bilateral scientific and technological cooperation between Republic of Croatia and Republic of Serbia
Project funding: Serbian Ministry of Education, Science, and Technological Development; Croatian Ministry of Science and Education
Project duration: 1st May, 2019 – 30th April, 2021

Participants: Serbian team: Mirjana Čolović, PhD (COST member); Danijela Krstić, PhD (COST member); Marko Dinčić, PhD student; Branislava Savić, PhD student;
Croatian team: Goran Gajski, PhD (COST member); Marko Gerić, PhD; Mirta Milić, PhD; Ana-Marija Domijan, PhD;

Short project description:
Acetylcholinesterase (AChE) is a serine hydrolase that terminates impulse transmission at cholinergic synapses by the rapid hydrolysis of neurotransmitter acetylcholine. Reversible inhibitors of this enzyme have been applied in the symptomatic treatment of Alzheimer’s disease associated with the loss of cholinergic neurons in the brain and the decreased level of acetylcholine.
Although the AChE inhibitor therapy results in improving cognitive abilities, the long-term application may induce undesirable side effects such as gastrointestinal problems and hepatotoxicity. For this reason, new compounds have been synthesized in order to find both efficient and less toxic pharmaceuticals for neurological disorders. Considering toxicity is a main limitation in the clinical application of physiologically active agents, the objective of this project is to evaluate in vitro prooxidative and genotoxic effects of synthesized metal-based compounds, promising anti-Alzheimer therapeutics exhibiting strong anti-AChE action.
(Posted on 10 September 2019)


On 28 March 2019 the 2nd conference validation of biomarkers took place in Basel, Switzerland.

Please find the presentations below:
(Posted on 25 June 2019)

The Netherlands X-omics Initiative is a new facility as part of the National Roadmap for Large-Scale Research Infrastructures. It is partly funded by NWO with a total budget of 40 million euro. The project started on September 2018 and will last for ten years.

The project aims to establish a X-omics research infrastructure across the Netherlands consisting of several existing facilities with various expertise’s related to molecular biology research (genomics, proteomics, metabolomics and data integration & analysis).

Through the project, we will:
1. Advance X-omics technologies far beyond state-of-art.
2. Realize an integrated X-omics infrastructure in the Netherlands.

Access will be provided to these facilities to enable researchers to use the newest X-omics technologies in their projects and drive new insights in biology.

A helpdesk will be created through which researchers can get into contact with our experts for advice on X-omics approaches in general or specific omics-related sample or data analysis challenges.

During the project, training schools will be set up with courses on X-omics approaches and several meetings will be organized to expand the Dutch X-omics community.

A proof of principle of the X-omics approach will be provided by starting 3 technological demonstrators on different levels (cellular, individual and population).

(Posted on 05 April 2019)

Biomarker commercialization (BiC)

A consortium to assist biomarkers reach their full potential.

Biomarkers are potential prognostic, diagnostic, and treatment indicators. Despite their increasing potential for precision medicine, their development into commercial products is very challenging. The purpose of a new Baltic Sea Region (BSR) consortium is to create tools for supporting and overcoming the challenges of biomarker commercialization.

The objectives of BIC consortium are to create:
- a biomarker development tool for researchers
- a screening and selection guide for TTOs
- a framework for technology translation into clinical setting
- new business model templates
- a biomarker platform with access to the tools and technology presentations for match making.
(Posted on 05 April 2019)

Systems approaches for the discovery of combinatorial therapies for complex disorders

Topic identifier: SC1-BHC-02-2019
Publication date: 27 October 2017
Types of action: RIA Research and Innovation action
DeadlineModel: two-stage
Planned: 26 July 2018
Deadline: 02 October 2018
2nd stage Deadline: 16 April 2019

Specific Challenge:
Many complex disorders pose a challenge to identify the most effective therapeutic interventions because current therapies often target specific aspects of a disease, without achieving complete control or the best possible results for patients. Due to the multiple causes of such diseases and the heterogeneity between patients, approaches directed at single targets have had limited efficacy, overlooking important factors involved in disease pathophysiology. Hence, a promising therapeutic approach to meet this challenge is to combine different therapies, while increasing therapeutic efficacy in a cost-effective manner.
(Posted on 23 July 2018)

Understanding causative mechanisms in co- and multimorbidities

Topic identifier: SC1-BHC-01-2019
Publication date: 27 October 2017
Types of action: RIA Research and Innovation action
DeadlineModel: two-stage
Planned: 26 July 2018
Deadline: 02 October 2018
2nd stage Deadline: 16 April 2019

Specific Challenge:
The increasing number of individuals with co-and multimorbidities poses an urgent need to improve management of patients with multiple co-existing diseases. A better understanding of their causative mechanisms is needed to develop early diagnosis, efficient prevention and monitoring, and better treatments adapted to co- and multimorbid patients throughout their life course. Furthermore, there are many different etiological models of comorbid conditions (e.g., direct causation model or a consequence of treatment). In this context, capturing and measuring patient's complexity in the context of co- and multimorbidities is crucial for adequate management of these conditions and requires innovative approaches.
(Posted on 23 July 2018)

ROBoCoP: a Respiratory disease Occupational Biomonitoring Collaborative Project

M Rinaldo, J Pralong, N Hopf, JJ Sauvain, G Suarez, P Wild, I Guseva Canu, Institute for Work and Health, University of Lausanne, University of Geneva, Switzerland

Chronic obstructive pulmonary disease (COPD) is a major public health problem with a prevalence in Switzerland reaching 15.9% in men. Exposure to particulate matter (PM) is a known COPD risk factor via oxidative stress pathway. Reactive oxygen species (ROS) and their metabolites could be predictive to COPD onset and be used as diagnostic biomarkers.

ROBoCop project, in the framework of CliniMark EU-COST Action, aims to select and validate a panel of oxidative stress biomarkers analyzed in non-invasive biological samples.

The research is divided into three studies:
- An experimental study aiming to standardize the biological sampling procedures and analytic techniques for oxidative stress biomarkers (8-isoprostane, malondialdehyde, NO2-, NO3-, formate ions and 8-OHdG) in exhaled breath condensate and urine and for oxidative potential in the exhaled air (OPEA) analyzed with our OPEA analyzer (EU and USA patent) a promising method in COPD diagnosis.
- A pilot study in the field, at a Parisian Transport Company (RATP) to determine the best time to collect samples and assess the suitability of the selected biomarkers in surveying RATP workers exposed to PM.
- A field study conducted among 300 RATP workers selected by stratified randomization from 45’000 workers. Statistical analyzes of medical examination (lung function test) and biomarkers data will aim to determine the associations of one or a panel of the selected biomarkers with obstructive syndrome (FEV1/FVC<70%).

Our results will allow us to validate a useful and cost-effective method in screening large populations at risk of COPD. It will also be useful in monitoring COPD evolution and severity in patients.
ROBoCop project is supported by the Swiss National Scientific Foundation and French RATP company and involves researchers and occupational physicians from Switzerland and France.
(Posted on 11 January 2018)

Waters MS Technology Days 2017: Evaluation of biomarkers predictive for Alzheimer's disease

During the Waters MS Technology Days 2017 in Basel (6/27) and Lausanne (6/27) research results were presented from a BDC study carried out in the group of Dr. Theo Luider at the Erasmus MC (Rotterdam) about development and application of an LC-MS assay to evaluate Pregnancy Zone Protein as potential biomarker for the prediction of Alzheimer's disease. Information about the meeting here.
(Posted on 24 August 2017)

EATRIS Conference, Prague, September 24-26, 2017

EATRIS, the European Infrastructure for Translational Medicine in which the BDC laboratories of profs Bischoff, Luider and van Gool are members, will hold its annual Translational Conference in Prague, September 24-26. Conference information here.
(Posted 17 May 2017)

Bridging the translational innovation gap through good biomarker practice

In collaboration with the European technology infrastructures EATRIS, BBMRI and ELIXIR, Prof van Gool and other scientists from the Biomarker Development Center published a comment in Nature Reviews Drug Discovery to join efforts in defining the Good Biomarker Principle guidelines that will support successful biomarker discovery and development activities. These guidelines will be defined in the COST action CliniMARK, initiated and coordinated by Dr Luider of the BDC. See comment here.
(Posted 10 May 2017)

CliniMARK Kick-off meeting

The CliniMARK network has the goal of establishing "Best Biomarker Practice" (BBP) guidelines to radically improve the process from biomarker discovery to clinical use. The kick-off meeting was held at the COST offices in Brussels on March 14, 2017. A plan was developed to define BBP guidelines and to apply these guidelines for the validation of biomarkers with COPD as an example. The next meeting will be held from October 5 to 7, 2017, at the Erasmus MC (Rotterdam) in conjunction with the Biomarker Symposium. For further information please contact This email address is being protected from spambots. You need JavaScript enabled to view it..
(Posted 20 March 2017)

COST action on good biomarker practice

Biomarker Development Center (BDC) leads new COST action 'CliniMARK' on good biomarker practice to increase the number of clinically validated biomarkers (COST Action number: CA16113) funded by the European Commission. This network comprises members from 16 countries including Canada and the USA.
(Posted 06 November 2016)

Europe Biobanking Week

The recent Europe Biobanking Week in Vienna focused on the use of biospecimens and was organized by BBMRI and ESBB. Eight hundred participants followed Prof. van Gool's lecture about the necessity of improving the quality and not the quantity of biomarker candidates and developing them into valid, clinically relevant assays. The slides of the lecture can be consulted here.
(Posted 12 October 2016)