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.”


Partnerships renewed at Harvard Medical School and EPFL

The Bertarelli Foundation has today signed gift agreements with Harvard Medical School and the École Polytechnique Fédérale de Lausanne that will secure and develop the Bertarelli Program in Translational Neuroscience and Neuroengineering. The new donations – totalling several million dollars – will fund the continuation of the education, research and knowledge-sharing program that was established in 2010. The signing of the gift coincided with the third annual Bertarelli Symposium, which took place in January at Harvard.

A unique partnership between American and Swiss universities, the Bertarelli Program brings together medics and scientists in neuroengineering to develop new therapies that will have real life-changing outcomes for patients with psychiatric and neurological diseases. It is this aim that really defines ‘Translational Neuroscience’ – marrying our increasing knowledge of the brain and nervous system with advances in neuroengineering to create results that are truly transformative. Among the research that is being undertaken are projects that are looking into cures for congenital deafness, as well as how we might combat paralysis – using electrodes and pharmaceuticals to reawaken the dormant circuitry that controls movement.

A further gift will establish the Bertarelli Catalyst Fund for the Dean of Harvard Medical School, with the goal of “supporting HMS priorities at the discretion of the Dean of the Faculty of Medicine.”

Commenting on the renewed partnership with EPFL and Harvard, Ernesto Bertarelli, Co-Chair of the Bertarelli Foundation, said:
“My family’s commitment to life sciences research goes back three generations. That is why we are particularly pleased to have cemented our association with these two world-leading institutions. The scientists on the Bertarelli Program are undertaking work that could herald astonishing and vital achievements – progress that could, potentially, improve the lives of many millions of people. The program also, I believe, serves as an example of what can be accomplished through real and meaningful collaboration.”

Image ©Steve Gilbert

The 2014 Bertarelli Symposium takes place at Harvard Medical School

At Harvard Medical School, 17-18 January, researchers and clinicians from the university joined colleagues from the École Polytechnique Fédérale de Lausanne for the third annual Bertarelli Symposium.

This year’s meeting coincided with the formal renewal of the partnership between the Bertarelli Foundation and the two academic institutions in the form of the Bertarelli Program in Translational Neuroscience and Neuroengineering, established in 2010. The new gift – totalling several million dollars – will help to “continue to inspire neuroengineering advances by bringing basic and clinical investigations together with experts in device design for sensory and other neurologic systems.” The Program’s defining aims are collaboration and innovation. 

The 2014 Symposium was entitled Neuroengineering:Molecules, Minds and Machines and it provided an opportunity to hear and discuss current efforts in translational neuroscience, not least initial findings from the first six research grants awarded through the Bertarelli Program in 2011.

Read more here about the programme for the 2014 Symposium, including case-studies of the pioneering research that is being carried out.

Commenting on the Symposium and the Bertarelli Program, Ernesto Bertarelli said:

“The strength of this program is in what it achieves as a whole—facilitating and encouraging scientists and medics from wholly different disciplines, backgrounds and, of course, locations to work together. I look, for example, at the work being done on paralysis and hearing problems and am heartened and excited by the fact that we have different research programs, from the two universities, working together, combining specialties and all with a common goal. It is how science should be, I believe.”

David Corey, director of the program at Harvard, said:

“In designing the Bertarelli Program, we needed to decide what neuroengineering really means. It combines engineering, neurology and neuroscience, yet it becomes more than the sum of its parts by focusing on new solutions for neurological and psychiatric disorders and seeking neuroscience knowledge that will be useful for patient care immediately rather than down the road. In just two years, it is clear the program is delivering on that vision.”

Image ©Steve Gilbert

Sir Robert Edwards, IVF pioneer

The Trustees of the Bertarelli Foundation were deeply saddened to learn that Nobel winner Sir Robert Edwards had passed away, as announced by Cambridge University.

The invitro-fertilisation procedures Sir Robert pioneered with Dr Patrick Steptoe changed the lives of many women and created new families across the world. The method they developed leads to optimal results when applied following controlled ovarian stimulation with human gonadotrophins. This was achieved with the drug Pergonal which was already used for ovarian follicular stimulation in infertile women. It was developed by Serono, the global biotechnology business built by three generations of the Bertarelli family.

Sir Robert received a Bertarelli Foundation Award in Reproductive Healthcare in 2000 and also advised the Foundation on its successful work to ensure effective monitoring and regulation of multiple embryo transfer with assisted reproductive techniques.

Approximately one out of every eight couples experiences difficulty conceiving. But until the middle of the last century, many of the causes of infertility were not fully understood, and there was little that could be done for women unable to become pregnant. This has changed with the development of Human Menopausal Gonadotrophins and was significantly further enhanced and expanded by the work of Sir Robert Edwards, which culminated in the world’s first test-tube baby, Louise Brown, in 1978. The outlook for infertile couples has changed forever, and the Bertarelli family are proud to have been a part of his important development.