Fondation Bertarelli Catalyst Fund
Diseases and injuries can severely affect the functions of the central and peripheral nervous systems as well as the sensory organs. To develop novel therapeutic approaches – gene therapy, optogenetics, bioactive molecules, diagnostic tools, imaging techniques, or implants, among others – the Fondation Bertarelli has donated CHF 5 million to create a Catalyst Fund. This fund is designed to foster innovative research and the development of life-saving treatments for diseases (including rare diseases) affecting the brain, the spinal cord, the peripheral nervous system, and the sensory organs.
Four calls for proposals were organized in 2017, 2019, 2020, and 2021. In total, 17 projects were selected for funding.
Prof. Carlotta Guiducci – EPFL
Prof. David Baud – Lausanne University Hospital (CHUV)
Preterm birth, defined as delivery before 37 weeks of gestation, is one of the main challenges in healthcare. Prematurity is the main cause of death of infants < 5 years old and children born preterm are likely to have long-term neurological and developmental disorders. It is essential to effectively identify pregnant women at risk of preterm birth (PTB). If the risk is detected on time, doctors could administer the required medical treatment for fetal lungs maturation and for fetal neuroprotection. Both treatments have to be given before birth to decrease pulmonary and brain injuries. Unfortunately, neonatal pulmonary injuries (resulting in damage to the nervous system) and brain injuries (resulting in cerebral palsy & damage to sensory organs) have a high risk to induce life-long comorbidities, with significant costs for the parents and the society. We are developing a medical diagnostic wearable, in the shape of a sanitary pad, that tracks biomarkers indicative of a risk of PTB. With one self-test/week, doctors can continuously follow up pregnant women at risk of PTB from home to anticipate an early delivery. By the end of the research plan, our goal is to commercialize our technology through a Swiss startup.
Dr Marzia De Lucia – University of Lausanne (UNIL), Lausanne University Hospital (CHUV)
Prof. Sophie Schwartz – University of Geneva (UNIGE)
The high misdiagnosis rate of patients with disorders of consciousness represents a global health and ethical challenge. The clinical diagnosis of such patients can be assisted by non-invasive electrophysiological investigations avoiding unfit withdrawal of life-support therapy. Prior to their clinical application, electrophysiological markers for the detection of consciousness have to go through a systematic validation in controlled settings. Sleep in healthy individuals provides such a rare setting where consciousness level can be inferred via well-known physiological and electrophysiological observations. In this project, Marzia De Lucia from Lausanne University Hospital and Sophie Schwartz from the Geneva Campus Biotech will investigate the neural response to cardiac and auditory signals in healthy individuals during wakefulness and sleep to validate a novel cardio-audio marker of consciousness. These are essential steps for implementing this marker in a clinical environment and improving diagnosis of disorders of consciousness patients’.
Prof. Sophie Schwartz – University of Geneva (UNIGE)
Dr Laurence Bayer – Geneva University Hospitals (HUG)
Anxiety disorders, characterized by excessive fear and anxiety, are the most frequent mental disorders with a substantial lifetime prevalence. The socioeconomic burden of anxiety disorders is considerable, as they reduce quality of life affecting work, social, and personal relationships. Exposure therapy is one of the most effective treatments of anxiety disorders, involving the gradual approach of the patient to feared situations, helping to overcome their distress by extinction learning. Sleep plays a key role in the consolidation of this type of memory, but what if the actual exposure therapy was carried out directly during sleep? We have recently demonstrated that eye parameters can be reliably tracked during sleep. Based on these initial findings, we will combine the expertise of sleep specialists, neuroscientists and clinicians working on sleep disorders and dreaming with the overarching objective to assess whether visual cues presented during sleep can be used to enhance extinction learning. These experiments promise not only to advance our understanding about visual information processing during sleep, but also lays the groundwork for innovative sleep-based therapeutic applications.
Prof. Friedhelm Hummel – EPFL
Prof. Grégoire Courtine – EPFL
Dr Estelle Raffin – EPFL
After a stroke not only motor processing, but also sensory processing is significantly impaired and alters dramatically the ability to move or to control movements. Though the importance of accurate sensory information and processing is well acknowledged for being able to perform movements well, it has not much been addressed in translational stroke rehabilitation research. Critical parts of the sensory network are deep in the brain and can so far only invasively be reached and modulated. However, in the present proposal the groups of Prof. Hummel and Prof. Courtine will use a novel innovative non-invasive method based on focussed ultrasound (fUS) to determine a currently described trans-thalamic sensorimotor pathway critically involved in sensorimotor processes. Within the project the potential for clinical translation of this innovative approach will be addressed in preclinical and human research and its underlying mechanisms determined by cutting edge neuroscientific methods. Establishing fUS for neuromodulation of deep brain structures of the sensorimotor network will open an exciting door towards novel, innovative neurotechnology-based rehabilitation strategies.
Bloch, Jocelyne – Lausanne University Hospital (CHUV)
Courtine, Grégoire – EPFL
Déglon, Nicole – Lausanne University Hospital (CHUV)
The adult human brain contains a reservoir of progenitor cells only found in the neocortex of primate species. These cells can be harvested from cortical biopsies, cultivated to produce so-called autologous neural cell ecosystems (ANCEs), and reimplanted into the brain to repair damage. For example, the principal investigators showed that ANCEs survive within host brain tissue where they proliferate into astrocytes and neurons that integrate endogenous neural networks. These grafts mediated functional recovery in nonhuman primate models of stroke and Parkinson’s disease, revealing the therapeutic potential of ANCEs for multiple neurological disorders. This functional recovery combined with the high safety profile of ANCEs convinced regulatory authorities to approve a clinical trial that will test the safety and preliminary efficacy of ANCEs in people with chronic stroke. However, this clinical application of ANCEs contrasts with our limited understanding of their biology. This knowledge is critical to optimize this cell therapy and identify new strategies to augment their efficacy. This project will leverage advances in single-cell technologies to understand the molecular profile of ANCEs, and how this profile evolves following the reimplantation of ANCEs in the vicinity of a stroke. The goal of this project is to leverage this understanding to develop improved treatments for brain repair.
Leggenhager, Bigna – University of Zurich
Blanke, Olaf – EPFL
Bekinschtein, Tristan – University of Cambridge
Chronic pain is a complex phenomenon, shaped by biological and psychosocial factors going beyond mere body damages. This collaboration between UZH, EPFL and the University of Cambridge develops a fully home-based, cost-effective method for assessment, characterisation and prediction of chronic pain. A new portable telemedical tool is designed to combine long-term brain and behavioural measurements with self-reports, all in a virtual platform running on the patient’s device. The principal investigators use the influence of attention on chronic pain and measure, in time, how spontaneous and experimentally induced attention fluctuations modulate pain changes in patients with Chronic Regional Pain Syndrome. These different measures provide rich and fine-grained information about the time maps of chronic pain and the underlying brain signatures beyond simple pain ratings. These results will facilitate the prediction of pain levels, tailored to each patient’s needs, and will thereby improve chronic pain rehabilitation, management and understanding.
Huber, Daniel – University of Geneva
Prsa, Mario – University of Fribourg
The joy of listening to music or even to a simple melody is one of the fundamental drivers behind human art and culture. This everyday pleasure is, however, not accessible to people with hearing impairments which affect over five percent of the population. Although classical hearing aids have made substantial progress, they still necessitate residual capacities along the auditory pathway and they do not retribute the complete range of the auditory spectrum. On the other hand, as we have all experienced during concerts, a small part of audible sounds, particularly in the lower range, is also transmitted by structure-borne vibrations and thus perceived by mechanoreceptors of the somatosensory system. This project will bring together expertise in sensory processing (Prof. Huber, University of Geneva) and biomedical engineering (Prof. Prsa, University of Fribourg) to explore new ways for transforming the wide frequency spectrum of audible sounds into the range of perceptible substrate vibrations in order to enable the hearing-impaired to enjoy the full spectrum of music. These studies will go hand-in-hand with the design and development of a novel type of portable vibrotactile stimulation device that enhances the range of information perceived by deaf individuals during musical events.
Krack, Paul – University Hospital Bern
Fleury, Vanessa – Geneva University Hospitals (HUG)
Blanke, Olaf – EPFL
Van de Ville, Dimitri – EPFL
Although Parkinson’s disease is primarily known for its motor symptoms (tremor, rigidity, slowness of movement), it is often accompanied by neuropsychiatric symptoms such as anxiety, a lack of motivation, depression, slowness of thinking and hallucinations. Those neuropsychiatric symptoms sometimes have a greater negative impact on the quality of life of patients than the motor symptoms. This study will investigate the underlying neuronal mechanisms of these neuropsychiatric symptoms by using resting-state fMRI. This new technique shows which areas of the brain interact which each other spontaneously, whilst the person who is lying in the scanner is at rest. In addition, the project will study the effect of dopaminergic Parkinson medication on the neuropsychiatric symptoms and on resting-state brain activity. This collaborative project combines expertise in neuropsychiatry of Parkinson’s disease (Prof. Krack, University Hospital Bern; Dr. Fleury, HUG), in neurorobotics (Prof. Blanke, EPFL), and in brain imaging (Prof. Van De Ville, EPFL). The aim of this study is to identify specific resting-state correlates of individual neuropsychiatric symptoms and their relation to dopaminergic medication. Identifying the underlying brain-networks of neuropsychiatric symptoms in Parkinson’s disease might help to improve their diagnosis and to adjust treatment strategies in the future.
Perren, Fabienne – University of Fribourg
Ryvlin, Philippe – Centre hospitalier universitaire vaudois (CHUV)
Blanke, Olaf – EPFL
Conventional transcranial ultrasound, as routinely used, has a limited use for cerebral vascular imaging and neurological application. Indeed, the skull bone in adults is a barrier to the propagation of ultrasound that strongly degrades imaging resolution resulting in poor imaging. To overcome this limitation, this project will develop and use for the first time transcranial ultrafast ultrasound neuroimaging in human adults. Ultrafast ultrasound imaging is a disruptive technology providing over 10’000 images/sec, whose first proof of concept for neuroimaging of brain vessels has been made very recently in Fabienne Perren’s research group by combining this breakthrough technology with contrast agent. This approach provides super-resolved maps of the brain vessels down to the capillary level (μm-scale). The project will include further technological developments to enable functional imaging of the adult human brain during cognitive tasks, both in healthy volunteers and in persons with epilepsy and cerebrovascular diseases.
Zysset-Burri, Denise – University Hospital Bern
Zinkernagel, Martin – University Hospital Bern
Although dry eye disease is considered to be one of the most common ocular surface diseases worldwide with a prevalence of up to 34%, treatment options are only very limited and severe side effects are common. However, recent studies showed that dry eye disease may be associated with bacteria located in the eye, called ocular microbiome. It has been suggested that bacteria are invasive in the tissue of the eye, thereby effectively hidden from clearance by the local immune system and resulting in chronic inflammation. Many ocular surface diseases are linked to a state of chronic inflammation, which is also a key component of dry eye disease. Since there is a crucial role of both, the ocular microbiome and the immune system, on several eye diseases, the overall aim of this project is to assess the associations of the local immune system and the ocular microbiome in dry eye disease. As the microbiome may be targeted by antibiotics and probiotics, this project may not only result in a better understanding of the disease mechanisms of dry eyes, but it may also have important implications for the prevention of dry eye disease and other immune-mediated diseases.