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Unravelling
the
secrets
of
the
brain

How Western Switzerland’s neurosciences cluster is turning research into innovation

Unravelling
the
secrets
of
the
brain

How Western Switzerland’s
neurosciences cluster is turning
research into innovation

Within a decade, Western Switzerland has become the Health Valley, a world-class laboratory for discovering and developing the healthcare of the future. Thanks to many visionary individuals, exceptional infrastructures and financial support, the Bioalps life sciences cluster has become one of the most dynamic and innovative in Europe. This “Odyssée by Bilan” offers a deep dive into the spectacular expansion of neurosciences in the Bioalps Health Valley. From fundamental research to start-up they have become key ingredients to make this region one of the fastest growing life sciences clusters in the world.

The
brains
who
uncover
the
secrets
of the
brain

How to make it simple? How to explain a biological machine that contains 100 billion glial cells and an equivalent number of neurons each interconnected by an average of between 1,000 and 10,000 synapses to allow information to circulate at speeds of up to 120 metres a second? How to explain emotions, consciences, dreams or love? And beyond that, how can you diagnose and cure the vast range of nervous system-related diseases that affect no fewer than one in three people worldwide?

Understanding the brain is one of the most noble missions science can pursue, because taxpayers who support universities also happen to be patients. Neuropathologies account for a third of health-related costs in Europe. With ageing, the number of people affected by Alzheimers and Parkinsons is due to explode in the coming years, threatening the very economic viability of health systems. Strokes are the leading cause of handicap. Multiple sclerosis affects 3 million people, placing an unbearable toll on families, friends and social workers. And the list goes on.

Because there are few if any cures for all these neurological problems, the neurosciences cluster of Western Switzerland with its Universities, Hospitals, start-ups and corporations has become a powerhouse to translate discoveries in the lab to the patient's bedside. The story of the brains exploring the brain on the shore of Lake Geneva has just begun. We hope you’ll enjoy discovering their odyssey and to see what is coming next.

Benoit
Dubuis

Neurological
diseases
in figures

Neurological diseases
Headaches top the list of the most common neurological disorders, followed by sleep disorders, strokes and dementia.

In Europe (743.1 million inhabitants), 220.7 million people suffer from at least one neurological disease – that is more than the populations of Germany, France and Great Britain combined.

Multiple sclerosis
About 2.5 million people around the world have Multiple Sclerosis.

Strokes
In the USA, every four minutes, someone dies of stroke.

Someone in the United States has a stroke every 40 seconds

Parkinson's disease
The annual increase of patients in the world reaches 2,5% because of aging.

About 10 million people in the world have Parkinson’s disease.

Alzheimer disease
In the last 10 years, the number of adults living with the neurodegenerative disease has jumped from 26 million to more than 36 million worldwide. Experts are predicting this number will reach 100 million by 2050.

How much do
you know about
neuroscience?

Campus
Biotech:
brains
inside

The former headquarters of Merck Serono have been transformed into a life sciences powerhouse with a strong focus on neurosciences. Its futuristic technological platforms attract the best scientists to the challenge of understanding, curing and perhaps enhancing the human brain.

“There remain two last big frontiers in science: space and the brain.” So spoke Patrick Aebischer 17 years ago when he became president of the Swiss Federal Institute of Technology in Lausanne (EPFL) and launched a breathtaking avalanche of initiatives that raised his campus to the top ranks of international universities.

Aebischer had a curious mind and under his leadership EPFL increased its support for a broad range of r esearch and disciplines. But as a neuroscientist himself he was naturally biased. So when pharma company Merck Serono decided in 2012 to close its headquarters in Geneva, he saw, together with Serono former owner Ernesto Bertarelli and Jean Dominique Vassalli, dean of the University of Geneva, an opportunity to build for neurosciences an equivalent to another science powerhouse in Geneva: CERN, the European Organisation for Nuclear Research.

New generation EEG to study the brain at the Wyss Center.

Building on solid Swiss and international networks, identifying future star professors and seizing public and private opportunities for research funding, a consortium including the University of Geneva, the EPFL, the Bertarelli family and Swiss medtech billionaire and philanthropist Hansjorg Wyss, gathered their energies to build Campus Biotech, officially launched in May 2015. Occupying 28,000 square metres, the futuristic facility currently employs 750 people, a number that will peak at close to 1,200.

The organisation functions under a foundation led by its founding partners and others including the University Hospitals of Geneva (HUG), the Swiss Institute of Bioinformatics (SIB), the University of Applied Sciences Western Switzerland in Geneva (HEPIA) and the newly created Wyss Center for Bio and Neuroengineering.

“Campus Biotech is mainly an enabler with four technological platforms giving access to top research tools such as virtual reality for experimental neurosciences, EEG an MRI for human neurosciences, electronics for integrative systems and clean room for neuroengineering”, explains Campus Biotech’s director Benoît Dubuis. A fifth platform with genomic tools such as sequencers and computational capability supports e-health and genomic research. But the most valuable assets of Campus Biotech are the brains it has attracted.

“The Lemanic community is a tremendously fertile area for new ideas."

Professor John Donoghue,
Director, Wyss Institute
at Campus Biotech, Geneva

Olaf Blanke’s
multisensorial
cognitive
engine

How does the human brain represent one’s own body? How does this bodily representation impact cognition and consciousness? How can we use robotics and information communication technology to better answer these scientific questions and translate this knowledge into concrete applications for the benefit of medicine and society?

Since his medical studies, Professor Olaf Blanke has made his mission to understand the brain mechanisms that enable consciousness. He heads the Laboratory of Cognitive Neurosciences (Bertarelli Chair in Cognitive Neuroprosthetics) and directs the EPFL’s Center for Neuroprosthetics and its eight laboratories which are currently moving to Campus Biotech. “Our second mission is translational,” Blanke explains. “We develop cognitive neuroprostheses that combine the design of new wearable technologies with our neuroscience research. The aim is to create novel strategies to better diagnose and restore cognitive functions in disease.”

“We have demonstrated that it is possible to reconstruct, in detail, a digital version of part of the brain."

Henry Markram,
Professor of neuroscience at the Swiss Federal Institute for Technology (EPFL), director of the Laboratory of Neural Microcircuitry and founder and director of the Blue Brain Project

Olaf Blanke

In neurosciences, Blanke’s team investigates the brain mechanisms of body perception, self-awareness and consciousness, combining psychophysical and cognitive paradigms with the whole range of human neuroimaging techniques. In its clinical research projects, his team of neuroscientists, medical doctors, biologists, engineers, psychologists and computer scientists explore the diagnostic and therapeutic impact of robotic and ICT technology in two major conditions: chronic pain and schizophrenia.

From labs
to market with
Claude Clément

Head of technology at the Wyss Center for Bio and Neuroengineering, Claude Clément comes from industry where he spent 23 years in the field of active implantable medical devices, as director of manufacturing engineering at Intermedics and plant manager at the Swiss operations of Medtronic, the world’s largest site for the assembly of active implantable medical devices.

Clement explains the Wyss Center’s objectives: “As a philanthropist, Hansjorg Wyss has trusted us with the mission to make paralytics walk again, the blind to see and the deaf to hear.” He adds: “It is in the very nature of the Wyss to collaborate. We are tackling difficult problems that generally need the involvement of multiple partners and institutions. We federate their human and technical means and solve aspects such as intellectual property sharing and regulation. Our approach is translational. We take the brilliant ideas that arise in academia and transfer them to clinical trials on humans. And we don’t stop at proofs of concept or prototypes. We support the product up to market approval.”

“Our laboratory is specialised in the production of in-vitro human nerve tissue derived from stem cells. We are able to respond very quickly to questions about biocompatibility tests or the resistance of different electrode networks that will subsequently be implanted into either animals or humans.”

Professor Luc Stoppini, Head of The tissue engineering laboratory at Campus Biotech and Hepia.

Claude Clément

For example, Professor John Donoghue, director of the Wyss centre is developing second generation brain-computer interfaces with an implantable neurocommunicator that can read brain signals of people with paralysis and transmit them wirelessly in order to control a robotic arm or even the patient’s own arm. A second project, led by Professor Diego Ghezzi in collaboration with Professor Micera, aims to develop a bionic implant that will bypass damaged optical cells and restore lost vision by directly stimulating the optic nerve. Based on discoveries by Professor Anne-Lise Giraud of the University of Geneva that oscillations in the brains of people with dyslexia are not at the correct frequency or in the correct location, a third project is using transcranial alternating current stimulation to reorganise brain rhythms so that signals are properly processed.

Can Daphne
Bavelier
enhance
learning?

If an understanding of the brain is needed to better diagnose and cure numerous pathologies, it has other consequences: what if we could improve it? Professor Daphne Bavelier, head of the Cognitive Laboratory of the University of Geneva, is exploring various technologies for such a purpose.

In 2014 her team published a study that demonstrated for the first time that people who played action games like "Call of Duty" showed greater capacity to learn than those who played non-action games. “We showed action gamers excel because they are better learners," explains Bavelier. "That is because our brain keeps predicting what will come next. To predict better, the brain constructs templates of the world. The better the templates, the better the performance. And playing action fosters better template construction.”

With a dozen colleagues at Campus Biotech, Bavelier has established collaborations with Olaf Blanke and professor Silvestro Micera to improve virtual reality and with Sophie Schwartz’s Sleep and Cognition Neuroimaging Laboratory, neural bases of language experts Anne-Lise Giraud and Narly Golestani as well as the group of computational neuroimaging led by Dimitri Van de Ville. Her research focuses on characterising the factors that may contribute to greater plasticity of the brain and wider transfer of learning.

The
time
of
neuro
startups

The recent burgeoning of neuroscience research initiatives in Western Switzerland is spinning off new biotech startups. Some have already started human clinical trials to meet unmet needs for the treatment of major neurological disorders.

An alternative
for parkinson
at Prexton

François Conquet

Prexton Therapeutics, based at Geneva’s incubator Eclosion, is developing a unique approach to treating Parkinson's disease. This progressive neurodegenerative disorder is caused by the loss of dopaminergic neurons in the brain centre for movement initiation and coordination. Current treatments try to replace dopamine or to mimic its effects by chronically administering patients with the dopamine precursor L-dopa, inhibitors of dopamine catabolic enzymes or direct dopamine receptor agonists. These treatments provide symptomatic relief in the early to middle stages of the disease, but lose their efficacy as it progresses. None of them has demonstrated neuroprotection which can delay the disease's progression.

Following research started at Merck Serono, Prexton stimulated a compensatory neuronal system that was not impacted by the disease. Some receptors (mGluR4) were strategically localised to counteract neurotransmitter imbalance and restore motor behavior. The company developed positive allosteric modulators (PAMs) to increase mGluR4 activity while minimising the likelihood of adverse effects. According to Prexton’s CEO and founder François Conquet: “This approach received a crucial validation when in 2014 the Michael J Fox Foundation selected us for a grant of $2 million and ranked our technology first in its category.”

In February 2015, this endorsement facilitated Prexton’s fundraising of $10 million in a Series A round followed two years later by a Serie B of $29 million. With these funds, Prexton was able to enter into a phase I clinical trial in the UK in March 2016 and in Phase II in July 2017.

Asceneuron’s
road to
alzheimer's

Dirk Beher

A spin-off supported by the Entrepreneur Partnership Program of Merck Serono and an initial investment of 5 million Swiss francs, Asceneuron is working to treat Alzheimer's disease with three complementary therapies. In particular, the company is developing a molecule to prevent the formation of neurofibrillary tangles by the dysfunction of a protein (tau) associated with the disease.

CEO Dirk Beher explains: “We chose to focus on the molecule tau, the lesser explored of the two major Alzheimer’s disease pathologies, because it gave us the chance to establish proof of concept first in another taupathie: progressive supranuclear palsy (PSP).” PSP is an orphan neurodegenerative disorder also associated with tau accumulation that could be faster and more tractable than Alzheimer's. “Since people are making slow progress with amyloid Beta (the other protein’s dysfunction associated with Alzheimer's), it is most likely we will need therapies for both pathologies to have success in humans,” he explains.

In 2015, Asceneuron announced the closing of a series A financing round of 30 million Swiss francs led by Sofinnova and joined by SR One, Kurma Partners and Johnson & Johnson Innovation. It has recently received regulatory approval for a pkase 1 trial of its oral tau inhibitor.

“The increase of Alzheimer’s with the ageing of the population has the potential to drive all health systems into bankruptcy in the decades to come."

Martin Velasco - angel investor and president of AC Immunne

Geneuro targets
the causes of
multiple sclerosis

Jesus Martin-Garcias

In 2016 Geneva-based GeNeuro succeeded in raising €33 million on Euronext, valuing the company at €190 million. “We have a very strong story”, explains Jesús Martin-Garcia, CEO of the company. “Our approach is unique because we target the very causes of diseases such as multiple sclerosis.”

Founded in 2006 as a spin-off of research conducted over 15 years at Institut Mérieux, GeNeuro has advanced rapidly over the past decade in the development of monoclonal antibodies targeting pathogenic effects of human endogenous retroviruses for treating autoimmune diseases. The company is currently developing the first treatment that directly targets a cause of multiple sclerosis.

GeNeuro has a €350 million agreement plus royalties with French pharmaceutical company Servier, which is funding multiple sclerosis clinical trials in exchange for worldwide licensing rights outside of US and Japan.

Mindmaze,
neurotech first
unicorn

Interview of Tej Tadi

Since Lausanne-based MindMaze announcement that it had raised $100 million in a round lad by Hinduja Group in 2016, company founder and CEO Tej Tadi has brought Switzerland into the small club of countries able to produce a “unicorn” -- a startup valued at more than the symbolic US $1 billion mark. In his new 7th-floor offices with breathtaking views over Lake Geneva and the Alps beyond, Tadi intends to leverage these new funds in an ambitious growth strategy. The company's spectacular fundraising has aroused great interest, but Tadi will not be diverted from the path he started on twelve years ago, rooted in the mission driving the Swiss Federal Institute of Technology in Lausanne (EPFL) to turn science into business where he started exploring the potential of virtual reality for rehabilitation of patients after brain strokes.

Incorporated in May 2012, MindMaze runs parallel strategies. "The idea was always to have a medical grade product," Tadi says, "plus a technology for other markets." This led to the development of MindPlayPro, a suite of interactive games for the rehabilitation of upper limbs, then to MindLeap, a virtual reality helmet associated with EEG. The company’s stroke rehab treatments were introduced into European hospitals in 2013 and in the US this year. Because VR is stimulating, patients are more likely to do their rehab, which drives MindMaze to develop a home version. And by syncing the physical body in all its expressive capacity with a digital avatar, MASK, its new product for the entertainment market, allows developers to build playable characters that emote in pre-real-time.

Deep brain
stimulation at
Aleva

André Mercanzini

A spin-off from Prof Philippe Renaud's Microsystems Laboratory at the Swiss Institute of Technology in Lausanne (EPFL), Aleva Neurotherapeutics had raised $42 million from renowned private and institutional investors such BioMedPartners, BB Biotech Ventures, Banexi Ventures Partners and Initiative Capital Romandie. In 2016 the last round was led by Greatbatch, a strategic lead investor contributing a total of $5 million to the transaction. In February 2016, Aleva and Greatbatch announced they had closed a strategic development, supply and manufacturing agreement. In addition, Aleva will combine their innovative directional lead technology with the proprietary neurostimulation platform of Nuvectra, a recent spin-off from Greatbatch.

Aleva Neurotherapeutics' neurostimulation technologies and devices are designed to be more precise and more efficient than currently available DBS approaches, while causing fewer side effects. Based on its proprietary microDBS technology, Aleva has developed two novel brain stimulating products with different functionalities. The first, called directSTIM, is a complete directional deep brain stimulation system for long-term therapy in Parkinson’s disease and essential tremor. The second, spiderSTIM, is a full solution for intra-surgical placement of DBS electrodes. The successful results of Aleva’s directSTN pilot study were published in Brain in 2014.

The
Valais
region,
european
nursery
for
neuro-
rehab-
ilitation

The
Valais
region,
european
nursery
for
neurorehab-
ilitation

The canton of Valais is reshuffling its cards in providing care to patients who suffer from serious injuries, paralysis and strokes. By 2020, the Rehabilitation Clinic SuvaCare (CRR) – the main actor in the field in Switzerland – will have merged with the Rehabilitation Research Institute (IRR). CRR already accommodates IRR on its premises, and sharing their expertise in research and medical quality control will create an organisation dedicated to clinical research. Meanwhile, CRR is tightening its bonds with the Swiss Institute of Technology Lausanne (EPFL). Apart from the half-dozen researchers who currently hold the school’s chairs in neuroprosthetics, a new chair in clinical neuroengineering and human-computer interaction has set up its headquarters in a brand new 300 square metre laboratory in Sion. Thomas Hummel was appointed head of the laboratory.

Clinical neuroscience is emerging as a new field of expertise in which the Valais region intends to be competitive. Once established, about twenty EPFL scientists will be working at CRR. This is an unprecedented development for a clinical entity more accustomed to surgeons, orthopedists and physiotherapists than to engineers and neuroscientists. The new field of expertise will be neurorehabilitation, that is to say all fields of technology that are required to support the replacement of any motor or cerebral function that has been lost in a patient, or indeed facilitate its recuperation.

Ongoing research gives a good picture of what is meant by "rehabilitation medicine 2.0", a form of medicine gradually coming to prominence. For example, Professor Grégoire Courtine’s team is working on being able to offer patients who suffer from partial spinal paralysis the hope of recovering their mobility. By using the mouse model and combining a chemical cocktail coupled to implant-induced electrostimulation of the nervous system, researchers have already managed to control in real time the way rats move and the height to which they can lift their hind limbs. Tests have already been carried out at Lausanne University Hospital (CHUV), and the robot platform that was developed for analysing walking ability is in Sion to tried out on patients at CRR.

By 2020, the Rehabilitation Clinic SuvaCare (CRR) will have merged with the Rehabilitation Research Institute (IRR).

By 2020, the Rehabilitation Clinic SuvaCare (CRR) will have merged with the Rehabilitation Research Institute (IRR).

The spiraling
costs of
neurological
and mental
disorders

Mental disorders
Mental disorders account for 44% of social benefits and invalidity pensions in Denmark, 43% in the United Kingdom and 37% in Romania.

Stroke
Stroke costs the United States $ 33 billion a year, including the cost of health services, drugs, and lost productivity.

Neurological diseases
In Europe, neurological diseases cost 336 billion euros per year (dementia: 105 billion euros, 64 billion strokes and 43 billion headaches).

Dementia
The annual costs of dementia are estimated at $800 billion worldwide.

The BioAlps team

Committee

President
Dr Benoît Dubuis
Director, Fondation Campus Biotech Geneva

Vice President
Mr Raphaël Conz
Economic Promotion Manager
Office for Economic Affairs (SPECo)
Canton of Vaud

Treasurer
Dr Massimo Nobile
“Life Sciences Initiatives”
The Ark Foundation

Members
Mrs Catherine Lalive d’Epinay
Economic Development Officer,
Department of Security and Economy

Mrs Anne-Renee Leyvraz
Technology Transfer and Communication
Manager, PACTT (TTO UNIL-CHUV)
Dr Sacha Sidjanski
Head of External Relations,
School of Life Science,
EPFL- Ecole Polytechnique Fédérale de Lausanne
Mr Roland Feger
Business Manager, Service of Economy,
Republic and Canton of Neuchâtel
Prof. Ian Marison
Director, Biofactory Competence Center, Fribourg. Professor, School of Engineering and Architecture of Fribourg,
University of Applied Sciences of Western Switzerland

Secretariat

Mr Ir Claude Joris
Secretary General
Ms. Magali Ribes
Executive Assistant

Address

BioAlps Association
C/o OPI
Ch. du Pré-Fleuri 3
1228 Plan-Les-Ouates
Switzerland

Contact

BioAlps Association
Phone +41 (0) 22 304 40 40
Email contact@bioalps.org
Web www.bioalps.org

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