Developed within the context of the RHENEPI consortium, this computer simulator opens up new possibilities for research into new treatments for epilepsy and identification of the convulsion risks associated with candidate drugs or environmental factors

Rhenovia Pharma, a leading biotech company specialized in biosimulation applied to the discovery of new medications, announces today that it has developed the first computer simulator for the biological mechanisms of epilepsy, validated by laboratory experiments. The simulator has been developed within the framework of RHENEPI, a consortium initiated and led by Rhenovia Pharma under the French government's ’Fonds Unique Interministeriel’ (FUI) to support applied research, and the competitive clusters Alsace Biovalley and Lyonbiopole.
 
The RHENEPI consortium brought together the biotechnology companies Rhenovia Pharma and SynapCell with academic research teams led by Dr. Antoine Depaulis from the Grenoble Institute of Neuroscience (GIN) and Dr. Laurent Fagni from the Institute of Functional Genomics (IGF) in Montpellier. RHENEPI received total funding of EUR 2.5 million in 2010 to develop the platform for the biosimulation of epileptic features.
 
The team, comprising twelve neuroscience researchers and engineers in physics, mathematics and bioinformatics, relied on Rhenovia Pharma's modeling and simulation technology. It was guided by first-rate neurologists. Researchers conducted a three-year program of interactive studies performing computer modeling supported by laboratory-based experimental validation.
 
A major advance with a range of applications
The simulator replicates the basic biological mechanisms underlying the signal transmission between brain cells and simulates its defects leading to epileptic patterns. Now operational, it should contribute to the prevention of epileptic seizures and lead to the discovery of new therapies.

The key applications of the simulator are as follows:

• Optimization of existing anti-epileptic treatments and the way they are administered (identification of the most effective and least hazardous combinations of drugs)
• Acceleration of research and development of new treatments for epilepsy (discovery and development of new molecules or synergistic combinations of molecules)
• Identification/prevention of epilepsy risks associated with environmental agents and how they interact (food, drink, drugs, pollutants, etc.)

“Developing a computer simulator for epilepsy posed a real scientific, technological and medical challenge,” said Dr. Serge Bischoff, CEO of Rhenovia and RHENEPI program director. “This challenge has been successfully met as a result of the combined talents of a consortium with multidisciplinary expertise and funding from the European Union, the French state, the Alsace region and the two SMEs involved, Rhenovia and SynapCell. Rhenovia is proud to have succeeded in developing an epilepsy simulator which represents a major advance, giving hope to patients and their families, particularly those whose epilepsy is resistant to current treatments or might become resistant.”

“We can quickly verify some of our working hypotheses where biosimulation is validated by experiments in animal models of epilepsy recognized by the medical community. More importantly, we can formulate new hypotheses,” said Dr. Antoine Depaulis, director of research at INSERM, France's national institute of health and medical research and director of the epilepsy team at the Grenoble Institute of Neuroscience (GIN). “Beyond the development of new treatments, biosimulation is a considerable asset in our exploration of the pathophysiology of pharmaco-resistant forms of epilepsy.”

“A significant proportion (30 per cent) of epileptic patients do not respond satisfactorily to the treatments available. They continue to experience fits, despite treatment. With all the consequences that this implies, all too often a combination of treatments is required. This puts them at risk of multiple serious adverse effects,” said neurologist Dr. Laurent Vercueil, a doctor at Grenoble University Hospital and general secretary of the French League against Epilepsy. “In this context, the discovery of innovative and original treatments is keenly anticipated. In silico research, based on models which challenge traditional conceptions, makes a decisive contribution in this respect.”

Epilepsy is a condition affecting around one per cent of the world's population. It is a major neurological disorder that affects people of all ages, but particularly children and the elderly (source: French League against Epilepsy).

A significant economic challenge
Rhenovia now intends to turn this technological innovation into commercial success. It will introduce the computer simulator for epilepsy to the pharmaceutical industry and biotechnology companies. This could be as a service provider, by working in partnership or in strategic alliances with them. These organizations will be able to improve the quality of their pipeline by identifying new treatments for epilepsy or repositioning existing molecules, also by providing their toxicology and safety department with prior assessment of the convulsion risks of candidate drugs targeting other pathologies.

The simulator could have other applications. It could be used by regulatory authorities to reduce the convulsion risk from chemical substances or pollutants (such as nanoparticles or pesticides). It could also be of use to the defense sector in identifying antidotes to chemical weapons which attack the nervous system.

Implications for employment
The development of the epilepsy simulator created four posts with the consortium's academic partners for the duration of the RHENEPI project. It also created three posts at Rhenovia and SynapCell which became permanent on completion of the project.

It is expected that further jobs will be created in connection with the commercial exploitation of the simulator.

A simulator complementing a world-first offering
This development consolidates Rhenovia's position as a world leader in central nervous system biosimulation (1). The biotechnology company now has two physiological biosimulation platforms. The first simulates neurotransmission in the hippocampus and the second, neurotransmission in the striatum, the two brain regions respectively responsible for learning and memory and motor control.

Rhenovia has used these physiological platforms to develop four disease-specific simulators which are now fully operational:

• RHENOMS EPI (epilepsy)
• RHENOMS OPs (organophosphate chemical weapons)
• RHENOMS COGNITION (cognitive impairments associated with Alzheimer's disease and schizophrenia)
• RHENOMS HUNT (Huntington's disease)

Intended for use in the pharmaceutical, nutrition-health and defense sectors, these simulators provide computer predictions of the positive or negative impacts of therapeutic agents as well as any kind of active compounds.

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About Rhenovia Pharma SAS
Rhenovia Pharma SAS is a French biotechnology company. It is a world leader in the application of biosimulation in the prevention and treatment of neurological, neurodegenerative and psychiatric disorders and diseases. The company was founded in 2007 by an international team bringing together managers from large pharmaceutical companies and world experts in neuroscience and nervous system modeling. Based in Mulhouse, France, Rhenovia today has around twenty members of staff in France, Switzerland, Germany and the US, where it opened a subsidiary in 2012. The company has generated over EUR 6 million in revenue in six years. It was able to break even in its third financial year. Rhenovia has launched a second round of funding to secure EUR 2.5 million by the middle of 2014 to accelerate its expansion.

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About SynapCell SAS
SynapCell SAS (CEO – Dr Corinne Roucard) is a biotechnology company specializing in central nervous system disorders. It provides the biopharmaceutical industry with innovative solutions in the field of drug discovery to evaluate the therapeutic effectiveness of designated molecules. Its skills include rare scientific expertise, biological modeling to predict diseases in humans, practical knowledge of neurophysiology and the use of powerful tools based on the analysis of neural network electrical activity. Founded in 2005, SynapCell has focused on developing innovative epilepsy solutions and bringing them to market. It has become an expert partner to manufacturers developing candidate drugs. Part of SynapCell's activity also concerns the development of new predictive solutions for disorders of the CNS.

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