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.

Stephanie Lacour to Direct EPFL’s Center for Neuroprosthetics

Professor Stephanie Lacour, the Bertarelli Foundation Chair in Neuroprosthetic Technology, is today – the 1st of February 2018  – to succeed Professor Olaf Blanke as Director of EPFL’s Center for Neuroprosthetics. She will take over from Professor Olaf Blanke, who has led the Center since 2012 when it was founded.

Professor Blanke, the Bertarelli Foundation Chair in Cognitive Neuroprosthetics, has been instrumental in establishing the Center as a major presence in its research field and in forging its first-rate reputation for clinical translation in neuroscience and neuroengineering. He was also pivotal to the successful move of the Center and its work to Campus Biotech, where he continued to build key alliances in the  development of a clinical research network throughout the Lemanic region and beyond.

Stéphanie Lacour holds the Bertarelli Foundation Chair in Neuroprosthetic Technology. She is Professor at the School of Engineering and leads the Laboratory of Soft Bioelectronic Interfaces. She is a founding member of the Center for Neuroprosthetics and an advocate for its interdisciplinary research. Professor Lacour brings cutting edge expertise in soft materials science and engineering to the CNP as well as innovative perspectives to help develop and deploy neuroprosthetic medicine. Her nomination at the CNP Directorship received unanimous support of the CNP faculties and EPFL Presidency.

Lausanne chosen to host the World Conference of Science Journalists in 2019

On October 28th, 2017 in San Francisco, Lausanne was chosen to host the 11th World Conference of Science Journalists (WCSJ), which will take place from in July 2019 at the SwissTech Convention Center on the campus of the EPFL / UNIL. This meeting, which takes place every two years, attracts more than a thousand journalists and science communicators from more than 60 countries. The Bertarelli Foundation was proud to officially back the successful bid.

In winning over the Board of Directors of the World Federation of Science Journalists, which oversees the event, the winning bid will see the WCSJ return to Europe after events in the US (San Francisco, 2017) and South Korea (Seoul, 2015). The Swiss – or Alpine bid – was launched by the Swiss Association for Science Journalism (ASJS), soon joined by its sister organisations in France (AJSPI) and Italy (SWIM). The theme and motto for the 2019 meeting will be “Reaching new heights in science journalism” and the conference will use the mountains as a symbol and common thread.

Following the news of the win, the Bertarelli Foundation is pleased to confirm that it will be the main sponsor of the 2019 meeting. Ernesto Bertarelli says:

“Congratulations to the Alpine team on their success! This is another demonstration of the Lake Geneva region’s global standing in science, technology and engineering. I am proud through the Bertarelli Foundation to support this showcase of Swiss innovation, which will also share global knowledge and experience in science with our partners from all over the world.”

We are very honored that Lausanne has been chosen to host this important event. We presented the project of a conference organized by and for science journalists, to defend, present and promote quality independent journalism in the media worldwide. An aspect that has helped us to win,”

said  Olivier Dessibourg, president of the ASJS.

The Lausanne candidacy was able to benefit, from the beginning, from the support of four major academic partners: EPFL, CERN, and the Universities of Lausanne and Geneva. In addition to scientific and academic support, the Lausanne candidacy has also been able to rely on important levers in Swiss political, media and economic circles (State Secretariat for Education, Research and Innovation, Presence Switzerland, City of Lausanne, Canton of Vaud), but also within the whole of Europe, notably through the European Commission, or institutions such as the Euronews channel, the French National Center for Scientific Research (CNRS) or the European Union. radio-telecommunications (EBU).

The Bertarelli Foundation would like to send their many congratulations to everyone involved in the Alpine team in putting together such an impressive bid.

Bertarelli Foundation partners with EPFL for Gene Therapy Research

The Bertarelli Foundation has given EPFL an additional CHF 10 million donation to further accelerate research into the treatment of neurological disorders. Five million francs will be used to create a gene therapy platform at Campus Biotech, which is EPFL’s base in Geneva. The other five million will be placed in a “catalyst fund” that will promote further interactions between projects run jointly by the various research teams based at Campus Biotech.

Gene therapy research in the Lake Geneva region is about to get a shot in the arm thanks to a large donation from the Bertarelli Foundation. When a disorder is caused by a defective gene, doctors can attempt to either lessen the symptoms or treat the underlying problem. Gene therapy works by replacing parts of the DNA or directly correcting the mutations in the gene that affect how other genes function. One of the objectives of the new Bertarelli Foundation Gene Therapy Platform will be to develop viral vectors for delivering therapeutic genes in cases of neurological disorders.

A collaborative approach

The platform will be set up at Campus Biotech, where biomedical research is already being carried out by numerous research institutions: EPFL’s School of Life Sciences, the Center for Neuroprosthetics, the Wyss Center for Bio and Neuroengineering, the Human Brain Project, the University of Geneva and Geneva University Hospitals. The platform will also be able to count on the support of the new Swiss genome center and its extensive DNA sequencing capabilities.

The catalyst fund (Catalyst Fund @ Campus Biotech) will support projects conducted jointly by Campus Biotech research entities. It will be run by a scientific committee led by Patrick Aebischer, neuroscience researcher and former EPFL president.

A renewed commitment

The Bertarelli Foundation’s commitment to EPFL’s research is nothing new. Three chairs in the Center for Neuroprosthetics, held by Olaf Blanke, Stéphanie Lacour and Silvestro Micera, have already received CHF 20 million francs from the Foundation. Recruitment for the fourth chair, in the field of gene therapy, has now started.. The person who will eventually fill this post will have academic responsibility for the platform.

The Foundation also supports the Bertarelli Program in Translational Neuroscience and Neuroengineering, a joint initiative run by EPFL and Harvard Medical School that began in 2011. “Our long-term commitment reflects our confidence in EPFL but also – and most importantly – our desire to support and drive forward the fields of research that will revolutionise tomorrow’s medicine,” said Ernesto Bertarelli.

Martin Vetterli, president of EPFL, said: “We are especially grateful to the Bertarelli Foundation for its advocacy and for its unwavering support, which allows EPFL and our partners to develop innovative technologies and treatments that benefit all of society.”

2017 Bertarelli Neuroscience Symposium

Friday 7th of April saw the sixth annual Symposium of the Bertarelli Program in Translational Neuroscience and Neuronengineering take place at Campus Biotech in Geneva. Bringing together the five Bertarelli teams from EPFL and Harvard Medical School, the Symposium provides an opportunity for progress to be shared, for ideas to be discussed and for plans to be made for further collaboration. Encouraging achievements, including findings yet to be published, were presented for each of the projects, which are addressing hearing loss, macula degeneration and motion-corrected fMRI for children with autism.

As well as the talks from the five Bertarelli teams, the audience heard from five former inspirational Bertarelli Fellows – students from EPFL who had, as part of the Education component of the Program, had spent a year in Boston conducting Master’s research with an HMS-affiliated laboratory – about their experiences and work. There were also four highly engaging keynote speakers who addressed topics in and around the theme of this year’s Symposium: Perception, Learning and Memory (Neuroengineering Persepectives). Harvard’s Margaret Livingstone spoke about modules in the brain and how they develop for our vision perception, while New York University’s Cristina Alberini presented her work on molecular mechanisms of long-term memory storage, in particular the role of the IGF-2 (Insulin-life Growth Factor) protein, previously unknown as having a role in neurobiology. They were followed by EPFL’s Johannes Gräff, who shared his lab’s work in the emerging field of neuroepigenetics and its potential implications for long-term memory storage, particularly for those with Alzheimer’s Disease and Post-Traumatic Stress Disorder. Finally, UPenn’s Michael Kahana gave fascinating insight into his work using mathematical modelling and computational techniques to study memory.

The Symposium drew to a close with words from EPFL’s President, Martin Vetterli, who spoke about how it was fitting that the Symposium was being held at Campus Biotech, a “fertile ground for interactions” and a “toy store for scientists.” He was followed by an impassioned speech from Sir Jackie Stewart, who urged those present to continue their drive to increase knowledge, to further progress in neuroscience, and to ensure that the next generation of scientists are given the teaching and the tools to solve the brain’s mysteries and illnesses, particularly Alzheimer’s Disease and dementia, an issue about which he actively campaigns. Lastly, Kirsty Bertarelli gave thanks on behalf of the Bertarelli Foundation to all who participated in the Symposium and to all who had combined to make it such a success.

Speaking afterwards, Ernesto Bertarelli said:

“This Symposium, at which our teams of scientists join together to share their work, is a demonstration of the mission of the Bertarelli Program as a whole: To foster collaboration, across continents and across disciplines. As with every Symposium we hold, to hear in person the extraordinary progress being made across our joint projects is to be hugely encouraged and I – and everyone in the room at Campus Biotech – left with great hope for what is being achieved now and what will be achieved in the future.”

Improved gene therapy restores hearing and balance in mice

Last week, David Corey, the Bertarelli Professor of Translational Medical Science at Harvard Medical School, and colleagues announced that they had identified a new viral vector for the delivery of genes to hair cells in the inner ear. Now, scientists in the US have published two papers that show that in preclinical tests improved gene therapy has restored hearing, to a much higher degree than before, and balance in genetically deaf mice.

The work, which was part-funded by the Bertarelli Foundation, follows on from the 2015 study that demonstrated the restoration of rudimentary hearing. The two new papers, which used a new vector to transfer the gene therapy, now report much improved hearing, down to 25 decibels, “the equivalent of a whisper.”

The first study, the senior investigators on which were Harvard’s Jeffrey Holt, Konstantina Stankovic and Luk Vandenberghe, showed that a new synthetic vector, Anc80, “safely transfers genes to the hard-to-reach outer hair cells”. Previously, vectors had only been able to penetrate the cochlea’s inner hair cells.

“We have shown that Anc80 works remarkably well in terms of infecting cells of interest in the inner ear. With more than 100 genes already known to cause deafness in humans, there are many patients who may eventually benefit from this technology.”

Konstantina Stankovic, Associate Professor of Otolaryngology at Harvard Medical School

The second paper used the new vector to deliver a “specific corrected gene in a mouse model of Usher syndrome, the most common genetic form of deaf-blindness that also impairs balance function.” The study, which was led by Harvard’s Gwenaëlle Géléoc, reported remarkable efficacy in restoring hearing to deaf mice that were treated soon after birth. The therapy also restored balance, “enabling the mice to stay on a rotating rod for longer periods without falling off.”

There is still a great deal of work to be done before the potential treatment can be bought to patients and the authors issued one caveat: Hearing was restored in mice that were treated straight from birth, but not in those when the therapy was delayed by 10 to 12 days. Further research will aim to determine the reasons for this, but as Jeffrey Holt, a co-author of the second paper, says, it is a “landmark study. Here we show, for the first time, that by delivering the correct gene sequence to a large number of sensory cells in the ear, we can restore both hearing and balance to near-normal levels.”

There is more in the news story on Harvard Medical School’s website, here.

 

Professor Howard Jones, 1910-2015

It is with much sadness, but also with pride for having had the privilege to know him, that the Bertarelli Foundation reports the passing of Professor Howard Jones, who, together with his wife Professor Georgeanna Jones, was a pioneer of IVF in the USA. Professor Jones was 104.

The Professors Jones were the founders of the prestigious Norfolk IVF programme, which gave birth to the first IVF baby in the US, Elizabeth Carr. Their programme flourished and, as well as its breakthroughs in reproductive medicine, crucially trained many specialists who went on to start their own, successful IVF programmes around the world. Their contribution to reproductive science and to families around the world cannot be underestimated.

Professor Jones was, for many years, a Board member of the Bertarelli Foundation during its focus on fertility and – a field he was an expert in – knowledge transfer. In 2002 he and his wife were awarded the Bertarelli Foundation Award in Reproductive Health, which was established in 2000 to “honour individuals or teams who, through their work or personal commitment, have raised awareness about the global problem of infertility, promoted greater patient access to treatment, broken new ground in scientific research or medical treatment, or made extraordinary contributions in other areas that support the goals of the Bertarelli Foundation.” He was much, much more than a worthy winner.

Professor Howard Jones was born in Baltimore, Maryland in 1910. After his BA degree, he graduated from the prestigious John Hopkins University School of Medicine in 1935. He was a Professor Emeritus of Obstetrics and Gynaecology at Eastern Virginia Medical School, and Chairman of the Board (honorary) of the Jones Institute for Reproductive Medicine. He also held the rank of Professor Emeritus at the Johns Hopkins University School of Medicine where, between 1967 and 1976, he served as Professor of Gynaecology and Obstetrics.

Professor Howard Jones was a pioneer in the true sense of the word – visionary, brave and ethical.

Gene therapy restores hearing in deaf mice

Study funded by Bertarelli Foundation is a collaboration between Harvard Medical School, Boston Children’s Hospital and EPFL which takes a step toward precision medicine for genetic hearing loss

Using gene therapy, researchers at Boston Children’s Hospital and Harvard Medical School together with colleagues at the EPFL have restored hearing in mice with a genetic form of deafness. Their work, published online on July 8th by the journal Science Translational Medicine, could pave the way for gene therapy in people with hearing loss caused by genetic mutations.

More than 70 different genes are known to cause deafness when mutated. Jeffrey Holt, PhD, a scientist in the Department of Otolaryngology and F.M. Kirby Neurobiology Center at Boston Children’s and an associate professor of Otolaryngology at Harvard Medical School, together with first author Charles Askew and colleagues at the EPFL in Switzerland, focused on a gene called TMC1.

They chose TMC1 because it is a common cause of genetic deafness, accounting for 4 to 8 percent of cases, and encodes a protein that plays a central role in hearing, helping convert sound into electrical signals that travel to the brain. Holt believes that different forms of genetic deafness may also be amenable to the same gene therapy strategy. Overall, severe to profound hearing loss in both ears affects 1 to 3 per 1,000 live births.

Ultimately, Holt hopes to partner with clinicians at Boston Children’s Department of Otolaryngology and elsewhere to start clinical trials of TMC1 gene therapy within 5 to 10 years:

“Our gene therapy protocol is not yet ready for clinical trials—we need to tweak it a bit more—but in the not-too-distant future we think it could be developed for therapeutic use in humans.  I can envision patients with deafness having their genome sequenced and a tailored, precision medicine treatment injected into their ears to restore hearing – this is a great example of how the basic science can lead to clinical therapies.”

Ernesto Bertarelli, Co-Chair of the Bertarelli Foundation, commented:

“The implications of successful gene therapy are profound and we are delighted to be associated with this study program.  These findings mark a defining moment in the way we understand, and can ultimately challenge, the burden of deafness in humans.   The results are testament to the immense dedication of the research team and their commitment to bringing best-in-class science ever closer to real-world application.”

2015 Bertarelli Symposium on Translational Neuroscience

Making the impossible possible

The 2015 Bertarelli Symposium on Translational Neuroscience and Neuroengineering was held today, Friday April 17th, at Campus Biotech, Geneva.

The Symposium brings together scientists from Harvard Medical School (HMS) and the École polytechnique fédérale de Lausanne (EPFL) to discuss the work that they undertake collaboratively as part of the transatlantic research programme of the same name. The aim of the Bertarelli Programme is to “bridge the existing gap between basic and translational neuroscience”.  It does this by supporting basic and clinical research oriented towards translational opportunities, by creating stronger ties among scientists, engineers and clinicians, and by training the next generation of leaders in the field.

Opened by Professor John Donoghue, Director of the Wyss Center at Campus, the 2015 Symposium was structured around three major themes: rehabilitation and robotics; hearing; and vision. There was also a fascinating analysis of the dynamics of brain networks in children with autism, led by Proessor André van der Kouwe and Professory Dimitri Van De Ville.

The morning session’s focus on rehabilitation and robotics saw Professors Silvestro Micera and Robert Howe update the audience on the remarkable progress being made in terms of robotic hands. This progress is both in terms of their mechanics, their means of sensing the environment to which they respond, the control they can now give, and, crucially, the characterisation of sensation that, through the use of implant electrodes, is now possible.

In the first afternoon session, attention turned to the research being done into both the diagnosis and treatment of hearing loss, a medical need that it is both undeniable and, as the audience heard, drastically misunderstood in terms of its scale, both now and in the future. Work being done in this area by the HMS and EPFL teams includes optical techniques for diagnosis and therapy, auditory brainstem implants, and gene therapy in mouse models of human deafness.

Closing the Bertarelli Symposium was the session on vision, opened by Professor Diego Ghezzi who spoke about neuroengineering approaches to vision restoration. Professor Ghezzi was followed by Professors Matthias Lütolf, Michael Young and Yvan Arsenijevic whose work, incredible as it may seem, is focused on tissue engineering the macula. Finally, Professor Thomas Wolfensberger, gave his keynote lecture, Vision Without Light: From Wacky Experiments to Current Clinical Applications of Retinal Implants.

The guiding principle of the Bertarelli Programme is collaboration and the breaking down of borders between disciplines, academic institutions and countries. The Bertarelli Symposium is the defining expression of this principle, bringing together a community of scientists and engineers to share knowledge, to hear about the work being done and to learn about the exceptional progress being made towards outcomes that are truly transformative for people’s lives.

Bertarelli Foundation research grants at Harvard and EPFL will tackle sensory disorders

The Bertarelli Program in Translational Neuroscience and Neuroengineering, a collaborative program between Harvard Medical School and the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland, has announced a new set of grants worth $3.6 million for five research projects. This is a further strengthening of the partnership between Harvard and Swiss scientists begun in 2010.

Three of the five projects will pursue new methods to diagnose and treat hearing loss. A fourth project focuses on the dynamics of brain networks in children with autism, and the fifth on cell transplantation strategies that could reverse certain forms of blindness.

The research projects were all selected for their scientific quality, the novelty of the approach proposed and the potential for genuine clinical impact. Three of the research projects are a continuation of the successful research projects from the Bertarelli Program, focusing on novel approaches to understanding or treating sensory disorders.

Commenting on the new research, Ernesto Bertarelli, Co-Chairman of the Bertarelli Foundation, said:

“When my family and I had the vision for this program, it was based upon bringing together scientists and medical specialists from different disciplines and countries to really push the boundaries of neuroscience and neuroengineering, creating a melting-pot of different talents, passions and visions united by a commitment to find ground-breaking ways to treat people and to make their lives better. What has been achieved since 2011 is highly encouraging. What might be achieved with these new research projects is just as exciting.”

To promote collaborations between US and Swiss based scientists as well as between neuroscientists and engineers, the funding conditions stipulate that each project be an equal collaboration between Harvard and at EPFL. This incentivises researchers to to find new collaborators with complementary skills. This in turn led to new interdisciplinary projects that combined technologies and approaches in novel ways.

Jeffrey S. Flier, Dean of Harvard Medical School commented:

“We are delighted at the continued generosity of the Bertarelli Foundation.  This type of forward-thinking support is exactly what’s needed to help us continue to unravel the profound complexities of the human brain.”

David Corey, HMS professor of neurobiology and Director of the Bertarelli Program for Harvard Medical School, said,

“The past 40 years of basic research in neuroscience have produced an extraordinary understanding of how the brain works, and how it can malfunction in neurological and psychiatric disease. We are now at a point where we can use this understanding to treat these devastating diseases. The Bertarelli Program in Translational Neuroscience and Neuroengineering combines basic neuroscience with the technology and problem-solving focus of engineering to accelerate the delivery of new treatments to the clinic. The tremendous success of the first round of projects has amply validated the vision of the Bertarelli Foundation in creating this unique collaborative program.”