March 20, 2015

Harvard and EPFL Join Forces in Research Projects to Tackle Blindness and Deafness Through Neuroengineering
New grants for five research projects awarded by the Bertarelli Program in Translational Neuroscience and Neuroengineering

New grants for five research projects awarded by the Bertarelli Program in Translational Neuroscience and Neuroengineering Boston/Lausanne (October 21, 2014)—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 USD 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.

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 incentivizes researchers to find new collaborators with complementary skills. This in turn led to new interdisciplinary projects that combined technologies and approaches in novel ways.

“We are delighted at the continued generosity of the Bertarelli Foundation,” said Jeffrey S. Flier, Dean of Harvard Medical School. “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."

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.” Bertarelli, a graduate of Harvard Business School, is also a member of the Harvard Medical School Board of Fellows.

For further information, please contact:

Harvard Medical School
David Cameron
617-432-0441
david_cameron@hms.harvard.edu

EPFL
Madeleine von Holzen
+41 21 693 22 66 / M +41 79 305 86 25
madeleine.vonholzen@epfl.ch

Bertarelli Foundation
Marie-Hélène Hancock - Hirzel.Neef.Schmid.Counselors
+41 22 340 28 45 / M +41 79 204 21 22
marie-helene.hancock@konsulenten.ch


The Ecole polytechnique fédérale de Lausanne (EPFL)
EPFL is an internationally top-ranked scientific research and educational institution on the shores of Lake Geneva. As one of two Swiss Federal Institutes of Technology, its trajectory over the past four decades is unparalleled—taking the lead in emerging fields of research such as bioengineering and energy technology, as well as expanding far beyond the Lausanne campus throughout Switzerland with satellite campus and international accords with other world-class universities. EPFL at a glance

The Bertarelli Foundation
The Bertarelli Foundation was founded in 1998 in memory of Fabio Bertarelli, the father of Ernesto and Dona. Today, the Foundation has focused its activities on two main areas: life sciences and marine conservation. Ernesto and Dona are the Foundation’s co-presidents, while their mother, Maria Iris, and Ernesto’s wife, Kirsty, are also Board members. Bertarelli Foundation website

Harvard Medical School
Harvard Medical School (hms.harvard.edu) has more than 9,000 full-time faculty working in 11 academic departments located at the School’s Boston campus or in one of 47 hospital-based clinical departments at 16 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Pilgrim Health Care, Hebrew Senior Life, Joslin Diabetes Center, Judge Baker Children’s Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital and VA Boston Healthcare System.



Annex: the five new research programs


Developing new methods for diagnostics of hearing loss

One of the great challenges in diagnosing hearing problems is that the physician cannot see the tissues and cells of the inner ear. In contrast, simple optical methods allow inspection of the retina of the eye. In this continuation proposal the researchers will collaborate to develop new imaging methods for the human inner ear. While they have previously showed that they can image the inner ear with minimal invasion, they will now extend advanced endoscopic two‐photon technology to allow subcellular imaging, they will use the fluorescence of two natural metabolic products to assess the health of the inner ear, and they will extend initial results to enable imaging of the whole hearing organ. These experiments draw on the highly complementary skills of the two investigators to develop new methods for diagnostics for hearing loss.


New generation of auditory brainstem implants

The cochlear implant, a device that bypasses the deaf inner ear to convey electrical signals directly to the auditory nerve, has been the most successful neural prosthesis over the past few decades, with over 200,000 in use worldwide. However, some patients cannot receive an implant due to a damaged inner ear or auditory nerve. In their 2011 Bertarelli project, the researchers optimized design and fabrication of experimental auditory brainstem implants, using high‐density, flexible electrodes. Experiments were short-term, and only in mice. In this project, they will extend the research to long‐term experiments in mice to test the safety, durability, and effectiveness of the devices. They will also extend the flexible electrodes to human tissue, to optimize the geometry and stimulation parameters that will allow eventual use in human patients.


Gene therapy to treat deafness

For more than a decade hopes have been pinned on gene therapy to correct inherited disorders in humans. There are, for example, over 300 distinct inherited forms of deafness, which cause congenital deafness in about 1 in 1000 newborns, and these might be treated by gene therapy to replace defective genes. A longstanding problem for gene therapy for hearing loss, however, is that very few viral vectors will enter the mechanosensory cells of the inner ear.

This continuation of a successful project from 2011 will explore new vectors to carry genes into these sensory cells and will broaden the range of treatable genetic deafness. The researchers will also use modern genome editing technologies to repair specific mutations that cannot be corrected by simple gene replacement.


Brain networks in children with autism

Functional magnetic resonance imaging (fMRI) has successfully allowed us to watch brain activity in humans during experimental tasks, revealing which brain regions are specialized for which computational functions. fMRI has also begun to be used to understand disorders of brain connectivity—the information flow between these regions. But movement of the head during imaging can distort the image, and children with autism tend to move more than others, impeding diagnosis.

These researchers will first develop methods to detect and correct for head motion in children and other difficult patients. They will then use fMRI scans of autistic children to test abnormal connectivity between brain regions, which is hypothesized as a cause of autism. Finally they will identify aspects of brain connectivity that correlate with specific types of autism, and ask whether connectivity can be improved with current autism treatments. These experiments will address general problems of fMRI in moving patients, with specific studies of autistic patients and the role of connectivity in this disorder.


Tissue engineering the macula

Retinal degenerative diseases are leading causes of incurable blindness and are often characterized by loss of the light-sensing photoreceptor cells. Because the regenerative capacity of the retina is extremely limited, cell transplantation strategies hold promise to restore lost function. Researchers have had some success in isolating the progenitor cells that can turn into photoreceptors, yet knowledge of the optimal stage of differentiation for transplantation is lacking.

The overall goal of this project is to develop cell lines that could be transplanted into the retina to reverse certain forms of blindness, and to discover drugs that could prevent or reverse retinal degeneration. This will be done in three stages: First, researchers will coax progenitor cells to become cone photoreceptors, the type of photoreceptor responsible for color vision and high-acuity vision. Second, researchers will engineer scaffolds that can support the growth and differentiation of these photoreceptors. The third stage is to use such scaffolds as a platform to test potential compounds that can reverse retinal degenerative disorders.



December 19, 2014

Progress Report on Grants Awarded in 2011





October 25, 2011

Harvard Medical School and Ecole Polytechnique Fédérale de Lausanne (EPFL) Launch Joint Program to Improve Quality of Life for People With Neurological Disabilities
$3.6 Million Grant from Bertarelli Foundation to Underwrite Cutting-Edge Research

(Boston, MA, October 24, 2011) Two of the world’s leading universities are joining forces to combine neuroscience and engineering in order to alleviate human suffering caused by such neurological disabilities as paralysis and deafness. Scientists, engineers, and clinicians at Harvard Medical School (HMS) and Ecole Polytechnique Fédérale de Lausanne (EPFL) will collaborate on six pioneering neuroengineering projects made possible thanks to a $3.6 million grant from the Bertarelli Foundation. Bringing together the best of U.S. medical science and Swiss bioengineering expertise, the researchers will employ the latest technologies in gene therapy, flexible electronics, optical imaging and human-machine interfaces to repair spinal injuries and hearing loss.

The collaboration launch will be celebrated at Harvard this weekend, the 28th and 29th of October, with a scientific symposium called “Neuroengineering Approaches to Sensory and Motor Disorders” that will bring together some of the world’s pioneers in the field.

“There have been huge advances in our basic understanding of the brain and the senses,” said David Corey, Director of the Bertarelli Program at Harvard Medical School, “but they have not been applied to neurological problems as quickly as we would like. This unique program will combine research advances in neuroscience with the special technologies and strategies of engineers, to speed new treatments to the clinic.”

“This is a unique chance to bring bioengineering solutions to clinical trials by combining HMS’s vast resources and skills at their university hospitals and EPFL’s distinctive combination of life science and engineering facilities,” says Patrick Aebischer, President of EPFL, one of Europe’s premiere universities for engineering, technology, and computer science.


Six Groundbreaking Research Projects in Translational Neuroscience

In five of the six inaugural research projects of the Bertarelli Program, basic scientists and physicians at HMS will be working with EPFL bioengineers to create new methods to diagnose and treat a wide range of hearing loss afflictions, from those that are genetically based to those caused by damage from excessive noise. A sixth project will build on novel research on spinal cord stimulation done in Switzerland, taking it a step further by implementing stretchable electronics directly on the spinal cord and attempting to rebuild severed connections through stem cell regeneration therapy.


Seeing how we hear

One of the great challenges in diagnosing hearing problems is that the physician cannot see the tissues and cells of the inner ear. In recent years, microendoscopes have been used experimentally to try to image the cells of the inner ear, but these rely on adding fluorescent dyes, something not practical for human diagnosis. At the same time, physicists have developed methods for imaging without dyes. For this project, a physicist from EPFL will collaborate with an HMS otologic surgeon to develop new imaging methods for the human inner ear. The researchers will use mouse and human inner ear tissue to optimize these new detection methods, learning, for instance, how to look through bone with long-wavelength light. Through imaging inner ear cells in animal models, they will set the stage for eventual clinical trials.

Konstantina Stankovic, Harvard / Mass. Eye & Ear Infirmary
Demetri Psaltis, EPFL


Gene therapy targets inherited deafness

About one in a thousand children are born with some form of hearing loss, often caused by inheritance of a mutant gene. For over ten years, researchers have looked to correct a variety of inherited disorders with gene therapy, a process in which genetically engineered viruses carry corrective genes into cells affected by a mutant gene. Some early failures diminished gene therapy’s promise, but new trials in humans have been remarkably successful and have raised hopes for conditions such as hearing disorders. A problem for gene therapy is that there are few viruses known to enter the inner ear’s sensory hair cells. A pioneer in use of viruses for hair-cell physiology from HMS and Children’s Hospital Boston and an EPFL expert in gene therapy for humans will collaborate to explore new viruses to carry genes into hair cells. Through restoring sensory cell function in mice with gene mutations that mimic human deafness, the researchers will attempt to correct inherited deafness in a live mouse. This research may clear a path for developing similar tools to restore hearing function in humans.

Jeffrey R. Holt, Harvard / Children's Hospital
Patrick Aebischer, EPFL


Treating deafness through regeneration

Much of the hearing loss that affects older people is caused by the death of sensory cells and neurons in the inner ear, a consequence of loud noise, infection, or certain drugs. This is often accompanied by tinnitus, an incessant sense of ringing in the ears. Unfortunately, these sensory cells do not regenerate they way skin or blood cells do. A first step in treating this hearing loss is to learn how to regenerate inner-ear sensory cells and neurons. Harvard scientists have recently learned how to isolate cells from a developing inner ear and to genetically reprogram them to proliferate into millions in a dish. The challenge now is to turn them into sensory cells and nerve cells. An HMS world expert in inner ear development will work closely with an exceptionally creative bioengineer from EPFL. By investigating molecular changes that occur in inner ear cells when they proliferate, and then using a micro-engineered screening platform to test thousands of compounds simultaneously, the researchers will seek to find factors that convert proliferating cells into hair cells or neurons. Finally, these factors will be tested in mice that are deaf from genetic or environmental causes.

Lisa Goodrich, Harvard Medical School
Matthias Lutolf, EPFL


Delivering drugs to treat hearing loss?

Once scientists learn to regenerate sensory cells in the laboratory, it is still a huge leap to make this happen in a human patient. The right drugs or chemical factors must be delivered to the inner ear, held in the right place, and released slowly over months, all without damaging the delicate sound-sensing structures. In this project, a pioneer in hair-cell regeneration from HMS will work with an EPFL bioengineer specializing protein engineering and nanotechnology techniques to develop new ways of delivering regenerative factors to the inner ear. Bound to hydrogels or packaged in novel "polymersomes” the factors will be taken up by the remaining cells, and will reprogram them to proliferate and morph into sensory cells.

Zheng-Yi Chen, Harvard / Massachusetts Eye & Ear Infirmary
Jeffrey Hubbell, EPFL / Institute of Bioengineering


New generation of auditory brainstem implants

The cochlear implant, a device that bypasses a damaged inner ear and conveys electrical signals directly to the auditory nerve, has been the most successful neural prosthesis of that past few decades, with over 200,000 in use worldwide. However a substantial fraction of patients are not candidates for a cochlear implant, and there has been great interest in developing a similar prosthesis that bypasses the damaged auditory nerve by directly stimulating the brainstem. But most attempts have failed, either because the electrodes inserted are not sufficiently flexible to conform to the neural tissue, or because the electrodes stimulate too broad a population of brainstem neurons. HMS specialists will investigate optical stimulation of the brainstem, using either intrinsic sensitivity to infrared light or modifying brainstem neurons to respond to blue light. EPFL will develop flexible electronics, combining electrical and optical stimulation, that conform to the contours of the brainstem and are easier to employ during surgery.

Daniel J. Lee and Christian Brown, Harvard / Mass. Eye & Ear Infirmary
Stéphanie P. Lacour, Philippe Renaud and Nicolas Grandjean, EPFL


Walking again

A complete spinal cord injury leaves a person paralyzed with no hope of recovery, because the brain can no longer send signals to body’s extremities. EPFL has already made groundbreaking research in spinal cord stimulation using electrodes and pharmaceutics to reawaken the dormant circuitry that controls the legs, allowing animals to walk again, but involuntarily. For this locomotion to become voluntary, signals must come from the brain. HMS is working on silencing two genes that could lead to the re-growth of the neural fibers severed in the accident, bridging the injury and re-establishing voluntary leg movement when coupled with stimulation.

Zhigang He and Clifford Woolf, HMS / Children's Hospital
Stéphanie P. Lacour and Grégoire Courtine, EPFL

The Bertarelli Program in Translational Neuroscience and Neuroengineering
The Bertarelli Program in Translational Neuroscience and Neuroengineering is a joint research and education program between Harvard Medical School and Ecole Polytechnique Fédérale de Lausanne (EPFL) in Switzerland to combine advances in basic neuroscience with engineering strategies and technologies, to improve the quality of life for people with neurological disabilities. The Program provides grants to support three-year collaborative research projects in neuroengineering, with a focus on novel approaches to understanding or treating sensory and motor disorders. To promote collaboration between U.S. and Swiss scientists, each project is carried out jointly by groups at Harvard Medical School and EPFL. The program was established in 2010 thanks to a generous commitment from the Bertarelli Foundation.

Harvard Medical School
Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School’s Boston campus or in one of 47 hospital-based clinical departments at 17 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Children’s Hospital Boston, Dana-Farber Cancer Institute, Forsyth Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children’s Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital, and VA Boston Healthcare System.

Ecole Polytechnique Fédérale de Lausanne (EPFL)
By combining the tradition of precision micro-technology in watch making with cutting-edge research in 21st century science, EPFL has become one of Europe’s leading technical universities—attracting top researchers and industrial partners from around the world. Logitech (an EPFL start-up beginning in the 1980’s), Nokia, Nestlé and Credit Suisse have set up R&D headquarters on campus, and many of its professors are counted among the best in their fields, making it one of the most important hubs for technology development in Europe. Taking its current form only at the end of the 1960s, EPFL leads some of Europe’s most daring projects: The Human Brain Project to simulate the human brain in a super-computer; TOBI, to develop non-invasive interfaces for disabled persons; The Steeper project, to reduce energy use ten-fold in computers; as well as other pioneering projects in the fields of medical imagery, neurosciences, robotics, computer science, transportation, and fundamental science.
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