$75m gift to Harvard Medical School will advance basic scientific discovery and therapeutic science

New atrium will be created and iconic campus building to be renamed

The Bertarelli Foundation has pledged $75 million to advance basic scientific discovery and therapeutic science at Harvard Medical School (HMS). The gift will set in motion plans to transform the outdoor courtyard of Building C – the last remaining unnamed building on the School’s iconic quadrangle in the heart of Boston’s Longwood Medical Area (LMA) – into an expansive, sky-lit atrium that will serve as convening and collaboration space for occupants of the building as well as the broader HMS community. In recognition of the gift, Building C will be named the Bertarelli Building following completion of the atrium’s construction.

“HMS is a world leader in health care innovation, translational research and cutting-edge discovery, and it continues to have an immense impact on the health and wellbeing of humankind,”, said Ernesto Bertarelli. “It has been my honour to have been a partner of the School for over two decades and I am delighted to continue to support the HMS community in its important work by helping to modernize these landmark facilities to keep pace with therapeutics innovation.” 

“Ernesto Bertarelli is an ardent supporter of both fundamental and translational research at Harvard Medical School,” says HMS Dean George Q. Daley. “He understands that in order to improve the health and well-being of patients, we must first support observations in the lab and then nurture and orient them toward interventions in the clinic. It is therefore fitting that the Bertarelli name will be inscribed in the marble of the building that personifies our commitment to both basic and therapeutic science.”

In addition to housing the departments of Cell Biology and of Biological Chemistry and Molecular Pharmacology, Building C – or the Bertarelli Building – serves as a hub for the HMS Therapeutics Initiative, which aims to advance therapeutics research, accelerate translation of discoveries into medicines, and educate and train the inventors of future medicines.

It is home to the recently opened Blavatnik Harvard Life Lab Longwood, a centerpiece of the Therapeutics Initiative that provides collaborative workspaces for early-stage, high-potential biotech and life sciences startups founded by Harvard students, alumni, postdoctoral scholars, and faculty.

“The Therapeutics Initiative is working to address the impediments that can hinder an idea in the lab from progressing toward a medicine,” says Executive Director of Therapeutics Translation Mark Namchuk. “A critical component to transiting that science is building the infrastructure where both basic and translational science can be supported, and Ernesto Bertarelli is doing just that with his generous gift.”

The planned atrium project, which is anticipated to begin in 2023 and be completed in 2025, includes enclosing the building’s existing outdoor courtyard, which is situated between the wet lab and dry lab arms of the Blavatnik Life Lab. The Building C façade was recently restored and will be preserved, and the new spaces housed within the atrium will be integrated into HMS’ historic campus fabric.

Ernesto Bertarelli with HMS Dean George Q. Daley and Harvard University’s next President Claudine Gay on the HMS campus

“The combination of breakthrough science and empowering partnerships, like the one with Mr. Bertarelli, that animates the LMA is nothing short of inspiring,” says Harvard President-elect Claudine Gay. “You can feel the future of human health taking shape around you.”

“I am honored that the Bertarelli name will become a permanent and prominent part of the Medical School’s quadrangle,” said Harvard University president Larry Bacow. “Ernesto is a great friend of Harvard and to me personally. His ambitious vision is exceeded only by his unwavering support. Harvard is all the better for both.”

The Foundation has been a long-term partner of Harvard Medical School for over a decade. The Bertarelli Program in Translational Neuroscience and Neuroengineering was established in 2010 to bridge the gap between basic and translational neuroscience, with its most recent symposium held in October 2022. It also endowed the Bertarelli Professorship in Translational Medical Science, held by David Corey, while the Bertarelli Rare Cancers Fund was established in 2019 by Dona Bertarelli. Ernesto, who is the current chair of the HMS Board of Fellows, has been a trusted and valued advisor to Deans of the School for over two decades.

2022 #BertarelliNeuro Symposium

On Monday October 17th, the New Research Building at Harvard Medical School (HMS) hosted this year’s Bertarelli Foundation Neuroscience Symposium, which returned as an event for its 9th edition after a three-year pandemic-enforced hiatus.

The theme of this year’s Symposium was Understanding and Conquering Pain, which was put together by HMS Professors David Ginty, Clifford Woolf and Bruce Bean, who together put together a packed agenda featuring neuroscientists from across the US and from Europe.

Having been opened with remarks by George Daley, Dean of the Medical School, the Symposium kicked off with its first keynote lecture, given by David Bennett from the University of Oxford, who gave a fascinating insight into Human Pain Channelopathies. The equally compelling second keynote at the end of the day was delivered by Stephen Waxman from Yale Medical School, whose talk – Huxley’s Science Fiction: Pain, Pain Genes and Pain Resilience Genes – was enthusiastically received by the packed audience. In between those two talks, scientists from HMS, the National Institutes of Health, Vertex Pharmaceuticals, the University of Pittsburgh, MIT, the University of Glasgow and the University of North Carolina, Chapel Hill, addressed topics on pain, from neuronal circuits to the discovery and development of selective NaV1.8 Inhibitors for the Treatment of Pain.

Ernesto Bertarelli
Ernesto Bertarelli closing the 2022 Symposium

Before a reception for speakers and guests, the Symposium was brought to a close with remarks by Dean Daley, David Corey (the Bertarelli Professor of Translational Medical Science at HMS) and then by the Foundation’s Ernesto Bertarelli, who, in in discussing the importance of the topic of the day said, “pain reminds us of how human we are” and that attempting to understand it better is one of neuroscience’s most important missions. With the research of the calibre that was highlighted at the Symposium, great strides are being made to doing just that.

The Foundation would like to express its thanks to its partner, Harvard Medical School.

First round of Bertarelli Rare Cancers Fund grants awarded

Following the establishment of the Bertarelli Rare Cancers Fund at Harvard Medical School (HMS) in 2019, the first round of grants was awarded in 2020, with more than $9 million distributed to nine teams representing more than 19 lead and co-lead investigators across HMS and its affiliated hospitals. Research kicked off this winter.

HMS Dean George Q. Daley said:

“This exciting new program will advance our capacity to prevent, treat, and cure rare cancers, which, combined, affect many tens of thousands of patients and their loved ones in this country each year. By building research capacity and cross-institutional collaboration, the fund helps us pursue our mission of generating new biological insights and treatment strategies that improve health for all.”

Dona Bertarelli commented:

“We have a shared ambition to conduct research and innovate for the good of society. It’s clear that there is a need and an opportunity to accelerate transformative rare cancer research, and it is my hope that the fund will create a community of researchers who will, in collaboration with scientists around the world, transform the understanding, treatment, and care of rare cancers.”

It can be hard to make research progress in a rare cancer. For instance, tissue samples are scarce and pharmaceutical companies have less incentive to develop drugs for small patient markets. Academic institutions such as HMS can be particularly helpful, Daley said.

With the fresh infusion from the Bertarelli fund, HMS is able to build the infrastructure, generate the knowledge, and strengthen the research communities for rare cancers that more common cancers benefit from.

The ultimate goal is to improve the detection, diagnosis, treatment, and prevention of rare cancers.

The gift “shines a spotlight on the needs of rare cancer research” and addresses some of those needs by “supporting promising new research, bringing researchers together, and showing patients that progress can be made,” said fund director Ed Harlow, the Virginia and D.K. Ludwig Professor of Cancer Research and Teaching in the Blavatnik Institute at HMS.

The first grants span basic, translational, and clinical science while linking junior and senior faculty across the HMS community. The multidisciplinary collaborations promise to approach problems from different perspectives and produce stronger science.

Grant recipients are investigating different individual rare cancers as well as genetic and molecular mechanisms that span multiple rare cancers.

The fund administrators plan to support projects that build biological tools for studying clear cell cancers, including cell lines, xenografts, and three-dimensional tissue structures known as organoids.

To learn more about the Bertarelli Rare Cancers Fund and the different projects, visit:

Six New Catalyst Fund projects @Campus Biotech

The Catalyst Fund – supported by the Bertarelli Foundation – has selected six research projects to fund this year. Led by professors from EPFL and other Swiss Universities, these projects all aim to develop new treatment options for neurological disorders.

Created by the Bertarelli Foundation in 2017, the Catalyst Fund aims to invest in translational projects targeting innovative approaches for diseases affecting the brain, spinal cord, peripheral nervous system and sensory organs.

“The Catalyst Fund is designed to foster innovative research and the development of life-saving treatments for diseases in neuroscience,” says Ernesto Bertarelli. As the third call for proposals is now complete, six projects were selected for a total of CHF 1,788,619. “I offer my sincere congratulations to the six newest laureates at Campus Biotech,” declare the Co-Chair of the Foundation. “Each of these teams is pursuing research in extremely important and potentially high-impact areas of neuroscience and it is a great honour to be able to add extra fuel to the collaborative fire that is driving their vital work. I want to thank the other applications who, this time, we unfortunately could not select.”

Pierre Magistretti, chairman of the Catalyst Fund, adds: “The task of the Scientific Committee has been very rewarding due to excellent quality of the proposed projects, but at the same time, making the selection of the top six successful applications was quite challenging. This initiative provides a unique opportunity to leverage the outstanding potential of the Lemanic Neurosciences to promote basic research and translational projects in this field.”

A successful year with 40 proposals

This year, the call for proposals was very successful. “It’s a great validation of the vision that we had for the Catalyst Fund that this year, the programme’s third, we had over 40 proposals”, said Ernesto Bertarelli. This extraordinary number, together with the fact that every submission was of a very high calibre, is a further proof that collaborative scientific research in Switzerland is in great health. I also warmly thank EPFL and the Catalyst Fund’s Scientific Committee for their superb work with this important programme.”

The scientists will use the proceeds to kick off their research and make rapid progress towards clinical applications.


More about the projects:

Using cell grafts to repair brain damage

One of the biggest challenges in neuroscience today is developing safe, effective methods for repairing adult nerve-cell damage caused by neurological disorders. In this project, a team of scientists led by Jocelyne Bloch and Nicole Déglon from CHUV and Grégoire Courtine from EPFL has come up with a cell therapy-based method that involves grafts of autologous adult brain cells. The cells can be harvested from cortical biopsies, cultivated to produce autologous neural cell ecosystems (ANCEs) and reimplanted into the brain to repair damage. Bloch’s team has already found that such grafts can mediate functional recovery in nonhuman primates suffering from Parkinson’s disease or the consequences of a stroke. The next steps will be to conduct clinical trials on stroke victims and to further study the molecular profile of ANCEs and how this profile evolves following the reimplantation of ANCEs.

Measuring and preventing chronic pain

Chronic pain is a complex phenomenon shaped by a variety of factors going beyond mere body damage. In order to assess, characterize and predict chronic pain, Bigna Lenggenhager from the University of Zurich, Olaf Blanke from EPFL and Tristan Bekinschtein from the University of Cambridge developed a method that can be conducted entirely from home. Patients use a portable telemedical tool to take brain and behavioral measurements and perform self-reports. Because pain is largely influenced by attention, the scientists are studying how fluctuations in attention – whether spontaneous or experimentally induced – modulate pain changes in patients. These measurements provide key information about the time maps of chronic pain and the underlying brain signatures. The team’s findings may eventually be used to facilitate the prediction of pain levels and thereby improve chronic pain management and understanding.

Improving brain-image resolution through ultrasound

The conventional ultrasound examination of brain activity, commonly known as transcranial color-coded duplex or transcranial Doppler ultrasound (TCCD/TCD), has limited use for neurological applications and cerebral vascular imaging in human adults. That’s because adult skull bones act as a barrier to the propagation of ultrasound, thereby degrading imaging resolution. In this project, a team of scientists led by Fabienne Perren from the University of Geneva is developing a new technique for ultrafast ultrasound transcranial neuroimaging. By combining this type of neuroimaging procedure with a contrast agent, they were able to obtain super-resolved maps of brain vessels down to the capillary level – the scale of a human hair. The team will work with Philippe Ryvlin from the University of Lausanne and Olaf Blanke from EPFL to perform a clinical validation of the technique on healthy volunteers and conduct clinical confrontation trials on patients suffering from epilepsy and cerebrovascular pathologies.

Hearing music better by feeling its vibrations

Over 5% of the world’s population suffers from hearing impairments preventing them from fully experiencing the joy of listening to music. Although standard hearing aids can help, they do not cover the full auditory spectrum. In this project, Daniel Huber from the University of Geneva and Mario Prsa from the University of Fribourg will examine new ways for transforming the wide frequency spectrum of audible sounds into the range of vibrations perceptible by the somatosensory system. This research 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 hearing impaired and deaf individuals during musical performances.

Observing Parkinson’s inside the brain

Parkinson’s disease is often accompanied by neuropsychiatric symptoms such as anxiety, a lack of motivation and hallucinations. In this project, Paul Krack from the University of Bern, Vanessa Fleury from Geneva University Hospitals (HUG), and Olaf Blanke and Dimitri Van De Ville from EPFL will use functional magnetic resonance imaging (fMRI) on resting-state patients to investigate the underlying neural mechanisms of these symptoms and better understand the effects of dopaminergic medication on these patients’ brain activity. The team’s findings could pave the way to improved diagnoses and better targeted treatment strategies.

Understanding the mechanisms behind dry eyes

In this project, Denise Zysset-Burri and Martin Zinkernagel from the University of Bern are studying dry eye disease – an ocular surface condition that affects some 34% of the world’s population. Their goal is to assess the associations of patients’ local immune systems and ocular microbiomes, and the role they play in disease development. The results could give doctors a better understanding of the underlying disease mechanisms and eventually lead to a broader range of treatment options. This research could also have important implications for the prevention of dry eye disease and other immune-mediated diseases, such as psoriasis and rheumatoid arthritis.


Amputees Merge with their Bionic Leg

Scientists, including from a lab of a Bertarelli Foundation Chair at EPFL, have helped three amputees merge with their bionic prosthetic legs as they climb over various obstacles without having to look. The amputees report using and feeling their bionic leg as part of their own body, thanks to sensory feedback from the prosthetic leg that is delivered to nerves in the leg’s stump. Djurica Resanovic lost his leg in a motorbike accident several years ago which resulted in amputation above the knee. Thanks to novel neuroprosthetic leg technology, Resanovic was successfully merged with his bionic leg during clinical trials in Belgrade, Serbia.

“After all of these years, I could feel my leg and my foot again, as if it were my own leg,” reports Resanovic about the bionic leg prototype. “It was very interesting. You don’t need to concentrate to walk, you can just look forward and step. You don’t need to look at where your leg is to avoid falling.”

Walking with instinct again

Scientists from a European consortium led by Swiss Institutions, ETH Zurich and EPFL spin-off SensArs Neuroprosthetics, with clinical trials in collaboration with institutions in Belgrade, Serbia, successfully characterized and implemented bionic leg technology with three amputees. The results appear in today’s issue of Science Translational Medicine.

“We showed that less mental effort is needed to control the bionic leg because the amputee feels as though their prosthetic limb belongs to their own body,” explains Stanisa Raspopovic, ETH Zurich professor and co-founder of EPFL spin-off SensArs Neuroprosthetics, who led the study.

He continues, “This is the first prosthesis in the world for above-knee leg amputees equipped with sensory feedback. We show that the feedback is crucial for relieving the mental burden of wearing a prosthetic limb which, in turn, leads to improved performance and ease of use.”

Wearing a blindfold and earplugs, Resanovic could feel his bionic leg prototype thanks to sensory information that was delivered wirelessly via electrodes surgically placed into the stumps’ intact nervous system. These electrodes pierce through the intact tibial nerve instead of wrapping around it. This approach has already proven to be efficient for studies of the bionic hand led by Silvestro Micera, co-author of the publication, EPFL’s Bertarelli Foundation Chair in Translational Neuroengineering, professor of Bioelectronics at Scuola Superiore Sant’Anna, and co-founder of SensArs Neuroprosthetics.

Resanovic continues, “I could tell when they touched the [big toe], the heel, or anywhere else on the foot. I could even tell how much the knee was flexed.”

Resanovic is one of three leg amputees, all with transfemoral amputation, who participated in a three-month clinical study to test new bionic leg technology which literally takes neuroengineering a step forward, providing a promising new solution for this highly disabling condition that affects more than 4 million people in Europe and in the United-States.

Thanks to detailed sensations from sole of the artificial foot and from the artificial knee, all three patients could maneuver through obstacles without the burden of looking at their artificial limb as they walked. They could stumble over objects yet mitigate falling. Most importantly, brain imaging and psychophysical tests confirmed that the brain is less solicited with the bionic leg, leaving more mental capacity available to successfully complete the various tasks.

These results complement a recent study that demonstrated the clinical benefits of the bionic technology, like reducing phantom limb pain and fatigue.

Bionic leg: from prototype to product

“We develop the sensory feedback technology to augment prosthetic devices,” explains Francesco Petrini, CEO and co-founder of SensArs Neuroprosthetics, and who is guiding an effort to bring these technologies to market. “An investigation longer than 3 months, with more subjects, and with in-home assessment, should be executed to provide more robust data to draw clinically significant conclusions about an improvement of the health and quality of life of patients.” This project was funded in part by the NCCR Robotics and by the Bertarelli Foundation.

How the bionic leg works: connection between body and machine

The fundamental neuroengineering principle is about merging body and machine. It involves imitating the electrical signals that the nervous system would have normally received from the person’s own, real leg. Specifically, the bionic leg prototype is equipped with 7 sensors all along the sole of the foot and 1 encoder at the knee that detects the angle of flexion. These sensors generate information about touch and movement from the prosthesis. Next, the raw signals are engineered via a smart algorithm into biosignals which are delivered into the stump’s nervous system, into the tibial nerve via intraneural electrodes, and these signals reach the brain for interpretation.

Intraneural electrodes are key for neuroprosthetics

“We believe intraneural electrodes are key for delivering bio-compatible information to the nervous system for a vast number of neuroprosthetic applications. Translation to the market is just around the corner,” explains Silvestro Micera, co-author of the publication, EPFL’s Bertarelli Foundation Chair in Translational Neuroengineering, professor of Bioelectronics at Scuola Superiore Sant’Anna, and co-founder of SensArs Neuroprosthetics. Micera continues to innovate in the field of translational neuroscience using intraneural electrodes, like the bionic hand, optic nerve stimulation, and vagus nerve stimulation for heart-transplant patients..

Mackenzie Mathis to hold EPFL’s fourth Bertarelli Foundation Chair

The ETH (strategic manager and supervisor of Switzerland’s federal institutes of technology and research)  Board has appointed Professor Mackenzie Mathis, from Harvard, to hold EPFL’s Bertarelli Foundation Chair in Integrative Neuroscience.

How does the brain constantly adapt the commands it sends to the muscles to make our body move? This apparently simple question is one that the scientific community has yet to answer. The way our brain adapts neural signals to external stimuli – like the things we see, touch and think – is a complex process. And we’re only just beginning to understand how it works.

Mackenzie Mathis, whose research focuses on exactly this question, was today appointed tenure-track assistant professor at EPFL. She will hold the Bertarelli Foundation Chair in Integrative Neuroscience, the fourth research chair supported by the Foundation. The other three are held by Olaf Blanke, Stéphanie Lacour and Silvestro Micera.

Mathis, born in 1984, is a multi-award-winning scientist and teacher. She currently holds a Rowland Fellowship – a prestigious position at Harvard’s Rowland Institute for outstanding young scholars who wish to carry out independent research immediately after obtaining their PhD. Mathis’ thesis, which she defended in 2017, focused on uncovering the neural circuits and mechanisms underlying sensorimotor learning in mice.

In her new role at EPFL, Mathis will continue her research into adaptive motor control using a mesoscale 2-photon microscope – technology she developed during her time at Harvard. The device, which supports large-scale brain imaging with a wide field of view, allows scientists to study how adaptation manifests in neural signals. She also brings with her a system known as DeepLabCut, which accurately tracks and quantifies limb movements. Mathis plans to develop the system further, using it to observe how the brain adapts during illness.

Professor Mathis, will take up her new post on August 1st, 2020. Her lab, in Campus Biotech Geneva, will be jointly part of the EPFL’s Center for Neuroposthesis (CNP) and Brain Mind Institute (BMI).

Two new Catalyst Fund @Campus Biotech Projects Announced

In 2017, the Bertarelli Foundation made available an amount of 5 million Swiss francs to support the development of some of the most innovative research carried out at Campus Biotech in Geneva. Five projects were selected in 2018. This year, two new projects were chosen by a jury chaired by Pierre Magistretti and were announced at the Bertarelli Symposium.

Sensory feedback for upper-limb prostheses

The first is led by Silvestro Micera, EPFL’s Bertarelli Foundation Chair in Translational Neuroengineering (on the left in the picture above). It aims to develop upper limb prostheses that can not only be directly controlled by analyzing nerve impulses at the residual limb, but also generate sensory feedback to the patient. “Our goal is to understand the basic mechanisms which allow the brain to exploit the sensory feedback and to feel the new hand as part of the body. This will increase the clinical impact of our research”, says Silvestro Micera.

Attentive to the translational dimension of research projects, the jury noted that this work is, in parallel, considering the use of a non-invasive “somatosensory substitution” system, applied to the skin, which already exists off-the-shelf, and a “somatosensory restitution” system, based on the internal stimulation of nerve fibres. The combination of the two approaches expands the spectrum of patients who could benefit from such treatment.

Deep brain stimulation in a non-invasive way

The second new Catalyst project is presented by Friedhelm Hummel, EPFL’s Defitech Foundation Chair in Clinical Neuroengineering (on the right in the picture). He is developing a non-invasive brain stimulation system to improve cognitive function in patients of mild cognitive impairment or brain injury. His approach is based on temporal interference stimulation: by applying two electric fields of different frequencies to the skull via electrodes, it is possible to generate focused stimulation of deep areas of the brain. “Supporting patients suffering from MCI or TBI to keep or regain their cognitive functions is of paramount importance and will impact significantly their daily life. Temporal interference stimulation offers a promising, innovative and non-invasive novel avenue to modulate important deep structures of learning and memory-related brain networks, which could not have been addressed so far non-invasively” says Friedhelm Hummel This might avoid the need for intracranial electrodes.

For the jury, this non-invasive approach to deep brain stimulation is particularly interesting, and could have a strong impact. While many questions remain open about the feasibility of some of the proposed therapies, specialists felt that the underlying innovation was compelling.

After awarding prizes of nearly 300,000 Swiss francs to each of these two projects, the Catalyst Fund still has CHF 2.92 million available for future projects, and a further call for proposals will be made in early 2020.

A Week of Science for Switzerland and the Bertarelli Foundation

An important week of science for Switzerland and for the Bertarelli Foundation concluded last Friday with the eighth annual Bertarelli Neuroscience Symposium, the fourth to be held in the country and the second at Campus Biotech. Alongside an audience of scientists and students, also in attendance were delegates from the World Conference of Science Journalists (WCSJ), which had taken place all week in Lausanne and for which the Bertarelli Foundation was proud to have been a lead supporter.

The WCSJ is a bi-annual event that brings together over a thousand science journalists and communication professionals from all over the world. At the conference in San Francisco two years ago, the Foundation supported Lausanne’s bid to host the 2019 edition and continued as one of three main sponsors for the event itself.

More than 1,200 participants in the conference, nearly 150 of whom received a travel bursary, came from 83 countries, including one delegate from Yemen, who had to travel to Cairo for three weeks to get a Swiss visa. Over the course of four days they enjoyed a packed programme of workshops, press conferences and speeches, including from some big names such as the Director of Russia’s Space Research Institute,  a NASA administrator, the BBC’s Director of News and Current Affairs, and the Director of CERN.

For Lausanne – home to EPFL and to the University of Lausanne – and for Switzerland, the WCSJ was an opportunity to demonstrate the importance of science and research to the region. And for the Bertarelli Foundation, it provided an opportunity to showcase the work it funds in the fields of neuroscience and marine science, as well as show its support for science journalism and for its vital importance in turning scientific research into stories and news that can be better understood by the public and, crucially, policy makers.

The Foundation had two among 40 stands in the exhibition space, on which scientists from the neuroscience and marine science programmes met with conference delegates to talk about their work, to explain new neuroprosthetic technologies that were on show, or in the case of the marine scientists, invite the journalists to experience the Indian Ocean – both above and below water – via a virtual reality headset, which proved very popular.

Dr Dan Bayley (UCL), a researcher from the Bertarelli Foundation’s marine science programme, transports a #wcsj2019 attendee all the way to the middle of the Indian Ocean with his VR technology

Three scientists from the Foundation’s marine science programme – Prof. Heather Koldewey (Zoological Society of London), Dr. David Jacoby (ZSL) and Dr. Dan Bayley (UCL) – also gave a live press conference with updates from their research (and those of their colleagues) in the British Indian Ocean Territory.

Bertarelli Marine Scientists, Heather Koldewey, David Jacoby and Dan Bayley at their press conference at the 2019 WCSJ

In what must be a first, two of the programme’s scientists joined via satellite technology live from the field on Nelson Island in the Chagos archipelago right in the middle of the Indian Ocean. They were joined by colleagues live from Mauritius and, together, discussed new research they have conducted on, for example, the impact on the marine environment derived from removing rats from islands, which benefits sea bird populations and thus, it seems, coral reefs and fish in the waters close to them.

Live from the Indian Ocean

On Friday, the conference’s last day, journalists split up to attend field trips all over Europe. Some went to CERN, some to IBM, some to The French National Centre for Scientific Research (CNRS) in Lyon, and some to Campus Biotech, in Geneva, where, during the morning, groups were taken around ten of the laboratories. And then in the afternoon, they joined the rest of the audience for the Bertarelli Symposium.

The theme of this year’s Symposium, which was put together by Professor Stéphanie Lacour, the Bertarelli Chair of Neuroprosthetic Technology at EPFL, was neuromodulation, the “alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body”.

Symposium speakers with Ernesto and Kirsty Bertarelli at Campus Biotech

Presentations were given by scientists from the four Catalyst projects at Campus Biotech, which the Foundation funds, as well as by two excellent keynote speakers: Professor Tim Denison from the University of Oxford discussed the design and deployment of bioelectronics platforms for translational neuroscience, while Professor Tobias Moser from the University of Göttingen gave a great presentation about how optogenetics will change the design of cochlear implants for people with hearing problems.

Keynote speaker, Professor Tim Denison (University of Oxford)

There was also a talk given by two of the past Bertarelli Fellows: EPFL students who were funded to go and study in a lab at Harvard Medical School for a year of their Master’s research. They talked about how formative the experience had been and why any students in the audience who were considering it, should go for it. There have been a total of 33 Bertarelli Fellows since the programme was initiated and five more will be heading to Boston next year.

Ernesto and Kirsty Bertarelli with four of the EPFL student Fellows who will be heading to Harvard Medical School this year

The Symposium, which was well attended, was closed by Foundation trustee, Kirsty Bertarelli. After her remarks, the audience moved to Campus Biotech’s main atrium for the closing ceremony of the WCSJ, to which journalists from other field trips in the region also came. There were speeches from Ernesto Bertarelli, from Olivier Dessibourg, the President of the WCSJ 2019 and from representatives of EPFL (Vice President of Education, Andreas Mortensen) and the University of Geneva (Vice-Rector, Antoine Geissbuhler), as well as a contemporary dance performance by Flux Laboratory on the Campus Biotech balconies. A fitting end to an important week for science in Switzerland.

Ernesto Bertarelli closing the Geneva leg of the WCSJ


Advances in Genetic Hearing Loss Research

Bertarelli Foundation-funded scientists at Harvard Medical School and Boston Children’s Hospital have published research that describes how they have used a novel gene-editing approach to salvage the hearing of mice with genetic hearing loss. They have succeeded in doing so without any apparent off-target effects as a result of the treatment.

The animals—known as Beethoven mice—were treated for the same genetic mutation that causes progressive hearing loss in humans, culminating in profound deafness by their mid-20s.

The new approach, described online July 3 in Nature Medicine, involves an optimized, more precise version of the classic CRISPR-Cas9 gene-editing system that is better at recognizing the disease-causing mutation seen in Beethoven mice. The refined tool allowed scientists to selectively disable the defective copy of a hearing gene called Tmc1, while sparing the healthy copy.

Notably, the researchers report, their system managed to recognize a single incorrect DNA letter in the defective copy among 3 billion letters in the mouse genome.

Much more work remains to be done before even a highly precise gene-editing therapy like this one could be used in humans, the researchers cautioned. However, they said, the work represents a milestone because it greatly improves the efficacy and safety of standard gene-editing techniques.

“Our results demonstrate that this more refined, better targeted version of the now-classic CRISPR/Cas9 editing tool achieves an unprecedented level of identification and accuracy,” said study co-senior investigator David Corey, the Bertarelli Professor of Translational Medical Science in the Blavatnik Institute at Harvard Medical School.

Furthermore, the team said, the results set the stage for using the same precision approach to treat other dominantly inherited genetic diseases that arise from a single defective copy of a gene.

Everyone inherits two copies of the same gene—one from each parent. In many cases, one normal gene is sufficient to ensure normal function that spares the individual from disease. By contrast, in so-called dominantly inherited genetic disorders, a single defective copy can cause illness.

From left: normal hair cells, untreated hair cells of Beethoven mice, treated hair cells of Beethoven mice.

“We believe our work opens the door toward a hyper-targeted way to treat an array of genetic disorders that arise from one defective copy of a gene,” said study co-senior investigator Jeffrey Holt, Harvard Medical School professor of otolaryngology and neurology at Boston Children’s Hospital. This truly is precision medicine.”

The mice carrying the faulty Tmc1 gene are known as Beethoven mice because the course of their disease mimics the progressive hearing loss experienced by the composer.

The full news story announcing the research is here.

Four new #BertarelliNeuro Research Projects Announced

The Bertarelli Foundation has awarded collaborative research grants to four teams of scientists representing Harvard Medical School, its affiliated teaching hospitals, and the Institute of Molecular and Clinical Ophthalmology in Basel, Switzerland, all focused on understanding and treating some of the most devastating sensory disorders, including deafness, blindness and pain.

The grants are designed to foster cross-disciplinary cooperation among leading basic, translational and clinical neuroscientists in an effort to propel discoveries from laboratory to clinic.

“Neuroscience is experiencing an exciting confluence of two advances: an explosion in our understanding of how the brain works and how it goes wrong in neurological disease and the staggering arsenal of new biological tools that can modify genes and cells to treat disease,” said David Corey, the Bertarelli Professor of Translational Medical Science at HMS.

“The new projects of the Bertarelli Program will combine these advances to develop new therapies for debilitating sensory disorders,” Corey said.

The three-year grants, which provide $300,000 in funding per project per year, are part of the Bertarelli Program in Translational Neuroscience and Neuroengineering.

Established in 2010, based at HMS and led by Corey, the program brings together scientists from a range of disciplines to help bridge the gap between basic and translational neuroscience and to address important research challenges that, once solved, promise to have life-altering outcomes for patients with sensory disorders.

The program was conceived by Ernesto Bertarelli as “a fusion of different talents, passions and visions united by a commitment to find groundbreaking ways to treat people and to make their lives better.”

“Sensory disorders represent a vital frontier in neuroscience, both because of the extent to which they affect people’s lives all over the world but also because treatments for many of them feel within our grasp,” Bertarelli said. “These four new collaborative research projects are cases in point. I am excited to welcome them to the Bertarelli Program and to follow their progress as, together, we work towards the ultimate goal: clinical solutions that will change people’s lives.”

The latest round of funding from the Bertarelli Foundation brings to 15 the total number of research grants awarded since 2010.

The four newly awarded grants are:

Toward a therapy for deafness and blindness in Usher syndrome

Two HMS neurobiologists studying the origins of deafness—Corey and Artur Indzhykulian, HMS assistant professor of otolaryngology at Massachusetts Eye and Ear—are joining forces with Botond Roska, an expert on retinal biology and eye disease at the Institute of Molecular and Clinical Ophthalmology in Basel, Switzerland, to develop treatments for a form of Usher syndrome. This genetic disorder arises from mutations in multi-tasking genes involved in the senses of hearing, balance and vision. Usher syndrome occurs in about 1 of 10,000 people and accounts for half of all inherited cases of combined deafness and blindness, according to National Institute on Deafness and Other Communication Disorders.

Corey and Indzhykulian’s work will focus on a particularly severe form of the disease, known as Usher syndrome type IF, characterized by profound deafness and absence of balance function at birth, along with progressive blindness beginning in a person’s 20s.

Because children with this form of the disease rely on their vision to compensate for their deafness and lack of balance, the eventual loss of sight can be particularly devastating.

The researchers will focus on developing gene therapy aimed at overcoming a hurdle that has stymied therapeutic efforts so far: the unusually large Usher 1F protein. Typically, researchers use a harmless virus, such as the common adeno-associated virus, as a delivery vehicle to carry a healthy copy of a gene into the target cells.

In this case, the targets are hair cells in the inner ear and photoreceptor cells in the retina. However, the DNA for the Usher 1F protein is too long to fit in the viral carrier. Corey, Indzhykulian and Roska will use three different strategies to overcome this barrier.

Preventing ‘hidden’ hearing loss 

HMS neurobiologist Lisa Goodrich is working with neurobiologist and cancer biologist Rosalind Segal and with cancer biologist and pediatric oncologist Loren Walensky, both at HMS and Dana-Farber Cancer Institute, to develop treatments for hidden hearing loss. This slow, insidious form of deafness is estimated to affect more than half of people age 60 and older.

Such hearing loss often occurs as a result of long-term exposure to loud noise that damages the sound-and-motion-sensitive hair cells inside the inner ear. Once damaged, these hair cells do not regenerate, and their gradual demise leads to hearing loss.

A growing body of evidence, however, suggests that hearing loss can also stem from breaks in the connections, or synapses, between the hair cells and the nerves that transmit the auditory signal to the brain. In other words, even when both the hair cells and the signal-conducting nerves are intact and functional, the frayed synapses between them can cause “hidden” hearing loss. When many but not all synapses are lost, for instance, words might be heard but not understood, especially in a noisy room.

A treatment that shields these critical connections from damage—or one that reverses preexisting damage—promises to improve the quality of life for millions of people with noise-induced and age-related hearing loss.

In an effort to protect and restore these connections, Goodrich, professor of neurobiology at HMS, Segal, HMS professor of neurobiology at Dana-Farber, and Walensky, HMS professor of pediatrics at Dana-Farber, are working to develop a therapy that activates a protein known to enhance axon integrity. The therapy builds on previous observations made by the researchers which shows that when this protein is loaded in a viral carrier and delivered to the auditory neurons of the inner ear, it can protect the synapses from noise damage.

The team’s goal is to determine whether delivering this protein could also protect the synapses when delivered after noise exposure. An additional goal of the research is to determine whether the approach could slow down or prevent age-related hearing loss that stems from the loss of synaptic connectivity between hair cells and auditory cells.

Helping the brain make sense of sound 

Hearing is essential for navigating the world and for basic survival. This complex process is made possible not only by the detection of sound by hair cells in the inner ear but also by the decoding and interpretation of those signals by specialized brain neurons. This signaling cascade requires the presence of synapses between nerve cells to enable the propagation of the sound signal from one cell to the next.

In early childhood development, these synapses are malleable, meaning they form, disconnect and reform with other neurons until a functional decoding system is established. The phenomenon, known as neural plasticity, allows the maturing brain to develop circuits that can process novel information. As a child grows older, plasticity declines and the neural connections get hardwired. Yet, certain sensory disorders can benefit from restoring some degree of plasticity.

For example, when an adult who has hearing loss receives a cochlear implant—a device that electrically stimulates the nerve from the inner ear to the brain —the brain must rewire some of its circuitry to decipher the new sensory input.

Neuroscientists Bernardo Sabatini, the Alice and Rodman W. Moorhead III Professor of Neurobiology at HMS, and Anne Takesian, HMS assistant professor of otolaryngology at Mass. Eye and Ear, are joining forces to identify ways to boost the plasticity of sound-decoding neurons. The ultimate goal of their work is the development of therapies that enhance neuronal rewiring as a way to boost the efficacy of cochlear implants and to treat age-related hearing loss—a development that could benefit tens of thousands of people each year.

The team’s efforts will build on Takesian’s recent discovery that a small subset of inhibitory neurons regulates the plasticity of the auditory nerve circuitry in development and later life. The work will also capitalize on Sabatini’s expertise in optogenetics—a genetic technique used to render neurons sensitive to activation by light—as well as his expertise in using viruses to illuminate neurons so that the connections among them are revealed.

Toward precision-targeted, non-opioid treatments for acute and chronic pain

Pain disorders take an enormous toll on human health and have been a major driver of the ongoing opioid epidemic. Beyond the physical and psychological suffering that pain inflicts, it cost the U.S. economy more than $600 billion a year in medical care and lost productivity, according to research estimates.

New non-opioid therapies, with no addiction potential and a robust safety profile, are urgently needed to stem the crisis. HMS neurobiologists David Ginty, the Edward R. and Anne G. Lefler Professor of Neurobiology, Bruce Bean, the Robert Winthrop Professor of Neurobiology, and Clifford Woolf, professor of neurobiology at Boston Children’s Hospital, are on a quest to develop such treatments.

The work builds on Ginty’s recent discovery of at least six subtypes of pain-sensing neurons, each of them likely responsible for a different kind of pain, such as joint or skin pain.

Ginty’s lab will focus on identifying unique markers for each pain neuron subtype and on mapping out the signaling trajectory for each, both to identify the body area they sense and the regions of the spinal cord and brain where they send nerve signals.

Bean’s team aims to unravel the molecular profile of each of these neuronal subtypes to identify the proteins on their surface that are good drug targets. Ginty, together with Woolf’s lab at Boston Children’s, will work to optically activate or silence each neuronal subtype to understand what kind of pain it produces.

Together, the team’s findings will provide a detailed structural and functional profile of each one of these distinct types of pain neurons, paving the way to precision therapies that target each specific type of pain. 

The Bertarelli Program in Translational Neuroscience and Neuroengineering was launched with a gift from the Bertarelli Foundation in 2010 to address some of the most important questions in medical neuroscience that, once solved, would have life-changing outcomes for patients across the globe. Its focus is not just on stimulating new cross-disciplinary research but also on establishing cross-border and cross-institutional working communities for knowledge sharing. The aim of these collaborations is to bridge the gap between basic and translational neuroscience by supporting basic and clinical research oriented toward translational opportunities; by creating stronger ties among scientists, engineers and clinicians; and by training the next generation of leaders in the field.

Harvard Medical School has more than 11,000 faculty working in 10 academic departments located at the School’s Boston campus or in hospital-based clinical departments at 15 Harvard-affiliated teaching hospitals and research institutes: Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, Cambridge Health Alliance, Dana-Farber Cancer Institute, Harvard Pilgrim Health Care Institute, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children’s Center, Massachusetts Eye and Ear/Schepens Eye Research Institute, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Spaulding Rehabilitation Network and VA Boston Healthcare System.

New Neuroscience Gift Will Tackle Sensory Disorders

The Bertarelli Foundation’s gift of $6.35 million to Harvard Medical School will support research to understand and treat sensory disorders

The Bertarelli Foundation is further increasing its contribution to neuroscience research with a gift of $6.35 million to Harvard Medical School (HMS).

Of this new gift, $5 million will support collaborative research projects focused on understanding and treating sensory disorders, which affect tens of millions across the world, but also which experts believe will be at the forefront of exciting new breakthroughs in neuroscience. The $5 million will also support core facilities that will serve as technology incubators. These facilities will develop new instruments and methods that enable previously impossible investigations.

The gift’s remaining $1.35 million will support the continuation of an international fellows program, bringing five graduate students from the École polytechnique fédérale de Lausanne (EPFL) to Boston to complete year-long academic projects in labs at HMS and its affiliated hospitals.

“In terms of scientific and medical research, Harvard Medical School remains at the pinnacle and I am very pleased we are able to develop our partnership with this new programme,” says the Foundation’s Ernesto Bertarelli, member of the HMS Board of Fellows, and a graduate of Harvard Business School. “The School’s openness to exploring new ideas and collaborating with others for the benefit of patients is very important. This new gift aims to support fresh thinking and enable scientists to take forward new ideas, through effective partnership and innovation.”

“I am confident that the next five to 10 years will see many new treatments for deafness, blindness and pain, and I think the projects of the Bertarelli Program, which encourage cross-disciplinary solutions, will be among the most exciting and effective,” says neurobiologist David Corey, the Bertarelli Professor of Translational Medical Science at HMS and the program’s director.

“The Bertarelli Program embodies our quest as physician-scientists to catalyze discovery from bench to bedside,” says HMS Dean George Q. Daley. “The scientists funded over the past eight years have pinpointed some of the most fundamental aberrations at the root of sensory and neurologic disorders, and they are developing treatments that promise to transform the lives of countless patients, thanks to the foresight and generosity of Ernesto Bertarelli and the Bertarelli Foundation.”

This new partnership with Harvard Medical School builds on the previous successes of the Bertarelli Program in Translational Neuroscience and Neuroengineering, a joint program between HMS and EPFL. Established in 2010, the program aims to help bridge the gap between basic and translational neuroscience and to help address important issues that, once solved, will have life-changing outcomes for patients.

Eleven grants have been awarded to date—six in 2011 and five in 2014—to researchers spanning Boston Children’s Hospital, EPFL, HMS, Jules-Gonin Eye Hospital, Massachusetts Eye and Ear, Massachusetts General Hospital and Schepens Eye Research Institute of Massachusetts Eye and Ear. Four additional projects will be funded later this year. Each will include a principal investigator at HMS and a collaborator from HMS, an HMS affiliate, or another institution in the United States, or any institution in the world.

One of the previous recipients of Bertarelli funding was Tina Stankovic, the Sheldon and Dorothea Buckler Chair in Otolaryngology at Massachusetts Eye and Ear and an associate professor of otolaryngology at HMS. Working together with Demetri Psaltis at EPFL, her project focuses on developing new methods for diagnostics of hearing loss.

“Private philanthropy is critical in allowing us to tackle difficult, high-risk, high-reward projects. The Bertarelli Program has set a very high standard in this regard, and I’m delighted that it will continue to do so,” says Stankovic.

Five proposals win initial “catalyst” funding at Campus Biotech

Researchers from Campus Biotech were invited to develop joint projects with partner research institutes and bid for funding from the Bertarelli Foundation. The laureates have been announced, on April 11th, during the 2018 Bertarelli Symposium held at Harvard Medical School.

Less than a year ago, Martin Vetterli and Ernesto Bertarelli announced the launch of the Catalyst Fund @ Campus Biotech. The aim of this five-million-Swiss Franc fund is to promote and accelerate translational research projects on the nervous system in which one or more teams from Campus Biotech (in Geneva) join forces with partner research institutes. The first call for proposals is now complete, and five projects have been selected for funding. “The proposals were of a remarkably high calibre,” says Patrick Aebischer, who chaired the selection committee.

Ernesto Bertarelli adds:

“We are delighted to provide funding for these projects. They each represent the vision of innovation and collaboration which led us to create Campus Biotech and make it the home of such partnerships between scientists and institutes in the region. Our congratulations to the recipients of this first round of grants and their shared aim of achieving transformative results for patients. We look forward to following the progress of their research.”

Each of the five projects will receive 300,000 francs, which will be used to kick start their research and which will aim to ensure that the results can be turned into clinical applications.

Optogenetic therapy to restore eyesight

The project proposed by Bernard Schneider (EPFL’s Brain Mind Institute) and Sonja Kleinlogel (University of Bern) aims to bring a method of vision restoration to the stage of clinical trials. One in 300 people is visually impaired owing to a loss of light-sensitive retinal photoreceptors, manifesting in pathologies such as age-related macular degeneration or retinitis pigmentosa. Sonja Kleinlogel’s novel optogenetic gene therapy works by introducing and stimulating synthetic protein into remaining retinal interneurons, turning these cells into “replacement photoreceptors” and ultimately restoring the patient’s natural vision. This therapy has already been tested in the lab but still lacks a viral vector adapted for humans that will guide the novel light-sensing protein efficiently to the right retinal cells.

Treating vision problems after a stroke

Motor and language impairment are common deficits after stroke, yet 30% of victims suffer from vision problems such as loss of parts of the visual field (hemianopia). The project headed by Friedhelm Hummel and involving four colleagues from EPFL, HUG, Hôpital du Valais and the Clinique Romande de Réadaptation (Sion) will use a multimodal approach by functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) simultaneously to map out activity in the visual system following a stroke to better understand the mechanisms of recovery. This will form the basis for rehabilitation strategies involving non-invasive brain stimulation and visual training. The third phase of the project is dedicated to determine potential biological markers allowing to predict individual treatment effects. This will pave the way for patient-tailored targeted therapies towards personalized medicine.

Treating hallucinations in Parkinson’s patients

More than half of people suffering from Parkinson’s disease experience hallucinations – a feeling of presence is one of the most common forms. The neurological processes at play have been studied in Olaf Blanke and Dimitri Van De Ville’s labs at EPFL and can now be triggered using robotic tools. By teaming up with Paul Krack (Geneva University Hospital), the researchers will be able to go further in exploring these processes in patients suffering from Parkinson’s. Their first objective will be to detect the bio-markers associated with these hallucinatory states and then develop non-pharmacological and non-invasive therapeutic approaches based on neurofeedback to counteract them. Their results may one day be applied to hallucinations linked to schizophrenia and other neurodegenerative diseases.

Restoring fine motor skills

A cervical spinal cord injury can lead to partial or total paralysis of the legs, arms and hands. Electrical stimulation applied to nerve fibers below the lesion has already proven effective at restoring leg movement and function. But this method will need to be significantly refined before it can enable patients to recover sufficient motor skills in their hands to carry out day-to-day tasks. Tomislav Milekovic (University of Geneva) and Marco Capogrosso (University of Fribourg) plan to carefully map out both healthy and damaged neural networks in an effort to identify the sections involved in controlling the hands. These signals could subsequently control the electrical stimulation delivered by an implant placed on the spinal cord below the injury.

Controlling the paths of pain

Nearly 20% of the population suffer from chronic pain. Yet such pain is still poorly understood and in many cases cannot be treated with drugs over the long term owing to side effects. Stéphanie Lacour (EPFL) and Isabelle Décosterd (Lausanne University Hospital – CHUV and FBM-University of Lausanne) focus on the hyperexcitability of pain nociceptive neurons and the ion channels that activate them. They are developing the tools needed to create a mechanistic model that could lead to innovative therapies – involving gene therapies, optogenetics and neurotechnologies. One of their goals is to develop an optoelectronic implant that can be applied to the sciatic nerve of mice, along with a platform for optical control and signal detection.