Three Dutch research groups to start within the ERA-NET NEURON ‘Synaptic Dysfunction’ programme

Research into disorders of the central nervous system

25 January 2018

Numerous neurological and mental disorders - such as epilepsy, migraine, autism spectrum disorders, schizophrenia and mood disorders - form an important societal challenge and are often a heavy burden for patients, their families and carers. To tackle the subject, the 'Network of European Funding for Neuroscience Research' (NEURON) has set itself the goal of coordinating research efforts across Europe and beyond to facilitate disease-related biomedical research that will improve our understanding of synaptic dysfunction.

NEURON Synaptic Dysfunction

With this call, NEURON mainly wants to promote multidisciplinary approaches and translational research proposals that combine fundamental and clinical research. The research must ultimately help to develop new strategies for prevention, diagnosis, therapy and rehabilitation. A total of 20 funding organisations in 17 countries have launched a joint transnational call for research proposals about 'Synaptic dysfunction in disorders of the central nervous system.’ A total budget batch of 12.4 million euros is available. Dutch researchers play a role in 3 of the 12 projects awarded funding. With this they have realised an extra investment of more than 3.5 million euros. One of the research projects has a Dutch project leader.

This is the second time that the Netherlands is participating in the research programme of the NEURON network. The participation is an initiative of the NWO temporary taskforce National Initiative Brain & Cognition (NIHC) and the Netherlands Brain Foundation and is part of the Top Sector Life Sciences & Health.

For more detailed information please read the press release from ERA-NET Neuron.

List of proposals awarded funding

The three proposals awarded funding that Dutch partners are involved in are listed below in alphabetical order together with a brief description of the project. The projects have a duration of three years.

IPS&BRAIN: A functional dissection of human nicotinic receptor polymorphisms linked to addiction and schizophrenia

Dutch partner: Prof. Huib Mansvelder, Amsterdam Neuroscience - Brain Mechanisms, VU Amsterdam

The consortium wants to clarify mechanisms that underlie nicotine addiction and schizophrenia. In both disorders genetic variants of nicotinic acetylcholine receptors are involved that increase the chance of addiction and schizophrenia, but we do not understand how that works. In our brain, the receptors are responsible for communication between nerve cells but the role of the genetic variants of these receptors is unknown. Besides fundamental studies to investigate communication between brain cells in the case of genetic variants, stem cells (iPS cells) from patients will be used to test possible therapeutic strategies.

Linking synaptic dysfunction to disease mechanisms in schizophrenia – a multilevel investigation

Dutch partner: Dirk Schubert, Donders Institute for Brain Cognition & Behaviour, Radboud University Medical Center

Patients with schizophrenia suffer from hallucinations, delusions, cognitive limitation and reduced functioning. There is currently no cure for schizophrenia: medication for schizophrenia has serious side effects and often does not lead to an improvement in daily life.

Extensive research has revealed that schizophrenia patients often exhibit changes in the DNA sequence in one or several specific genes that increase the chance of schizophrenia (so-called risk genes). Further it is known that in schizophrenia patients various areas of the brain do not communicate well with each other. As a result of this, neuronal communication in the entire brain is disrupted. To gain a better understanding of schizophrenia we want to know what exactly goes wrong in the neuronal communication of schizophrenia patients and how the disrupted communication is associated with risk genes for schizophrenia.

As the SYNSCHIZ project investigates disease patterns related to schizophrenia at several levels – from gene to brain networks – new insights will be obtained into the exact biological mechanisms. A better understanding of these mechanisms could result in the development of new biomarkers. These will be used to diagnose the disease in an earlier stage before severe symptoms are manifested. As a result of this, doctors will be able to treat the disease faster and provide support to patients at an earlier stage.

SNAREopathy: Mechanisms of neuropsychiatric genetic diseases of the SNARE complex: towards therapeutic intervention

Project leader: Ruud Toonen, Center for Neurogenomics and Cognitive Research (CNCR), VU Amsterdam

The consortium will investigate mechanisms that underlie severe forms of epilepsy. About 1% of the world population suffers from epilepsy and 30% of patients do not respond to medication. More mechanistic knowledge is needed to develop new treatment methods for these patients. The consortium will study models of genetic epilepsy that are caused by defects in proteins responsible for communication between nerve cells. These defects disrupt the normal brain activity, which can cause epileptic seizures. With a combination of different model systems, from behavioural research in worms to electrical conduction in the nerve cells of patients, and the unique complimentary expertise in the consortium, the researchers expect to be able to provide important insights into the treatment of this large group of epileptic patients. The use of patients’ own nerve cells, obtained by means of reprogramming skin cells from the patient, will enable the consortium to carry out not just fundamental studies into the underlying mechanisms but also to test new therapeutic strategies on the most relevant cells, the patients' own nerve cells.

Source: NWO