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Professor Schambach was awarded approximately two million euros from the European Union for his “iHEAR” project / New gene therapies shall protect children and adults from hearing loss
High accolades for a Hannover Medical School (MHH) researcher: Professor Dr. Dr. Axel Schambach was awarded the very prominent “Consolidator Grant” from the European Research Council (ERC). The award will support his research project with approximately two million euros for the next five years. The Director of the MHH Institute of Experimental Hematology will use these funds for the “iHEAR” project, which has the long-term goal to protect children and adults from hearing loss and deafness.
A great number of people are afflicted with hearing loss: approximately 2-5 per 1000 children are born deaf. Additionally, around 20% of the world´s population will experience hearing loss during their lives. In Germany, around 15 million people suffer from severe hearing loss and (complete) deafness. There is currently no cure for hearing loss and those affected have to live with the challenges associated with hearing loss, such as social isolation and difficulties to participate in schools as well as to be successfully integrated into the job market. Cochlear implantations can be used to improve hearing for some patients, but the biological cause of the hearing loss remains untreated. Loss of function mutations in one or more genes linked to hearing loss are detected in about half of the children who are born deaf. Thus far, genetic analyses have identified approximately 100 genes that play a role in hearing loss when their function is disrupted by mutations.
The “iHEAR” team plans to use gene therapy approaches to treat hearing loss and deafness. Initial efforts will focus on genes that are critical for the function of the inner ear sensory cells required for hearing – namely the inner ear hair cells and spiral ganglion neurons. Delivery of corrected genes into these and other cells of the sensory epithelium will allow expression of the missing/defective protein and thus repair the cellular function.
Healing and Protection – for all Ages
The “iHEAR” team will also employ gene therapy to prevent acquired hearing loss, which can occur as a result of treatment with medications such as chemotherapeutics. In this approach, gene therapy will be used to provide the inner ear cells with the capacity to pump the medication out of the cells, thus protecting these sensitive cells.
The initial studies will be accomplished in cell lines and mouse models of hearing loss. Patient-specific hearing loss models based on induced pluripotent stem cells derived from hearing loss patients will also be developed to accelerate clinical translation of these approaches. In addition to children and young adult patients, the iHEAR research team expects that this work will lead to improved treatment for a broad range of hearing loss patients: “We hope that our results will also contribute to improved treatment of age-related hearing loss.”
Team work leads to success
This successful grant application is testimony to the importance of team work. “The new iHEAR project would not have been possible without the preliminary results that were achieved within the framework of the Excellence Clusters ‘REBIRTH – From Regenerative Biology to Reconstructive Therapy’ and ‘Hearing4all’, said Professor Schambach. For example, the gene transfer technologies critical for the iHEAR project were developed over more than twelve years of work in the framework of the Excellence Cluster REBIRTH.
Important contributions to the “iHEAR” project were made by Professor Dr. Brigitte Schlegelberger and Dr. Bernd Auber from the MHH Institute for Human Genetics, as well as PD Dr. Athanasia Warnecke, who is a medical doctor in the MHH Ear, Nose and Throat (ENT) Clinic. “Gene therapy will allow entirely new possibilities to treat severe hearing loss. Gene therapy provides us with the opportunity to correct the cause of the hearing impairment, and, thus, direct the healing process. The grant is an extraordinary complement of the excellent interdisciplinary work accomplished by the young MHH researchers”, explained Professor Dr. Thomas Lenarz, Director of the MHH ENT Clinic and Speaker for the Hannover chapter of the Excellence Cluster Hearing4all. Dr. Warnecke sees the complex cell architecture of the inner ear as a great challenge. “In our plans to use gene therapy to treat hearing loss, it is imperative that we can repair exactly those structures that are defective and only in those cells in which the structures naturally occur”, she explains.
The Administrator of the Center for Regenerative Medicine, REBIRTH, is also extremely pleased about the ERC award. “As one of many applications that were developed in the Stem Cell Research Area in REBIRTH, the funded concept can now explore completely new research applications, namely, stem cell based disease models and the protection of cells from damage due to chemotherapy. If successful, these highly innovative technologies designed for the inner ear could also be applied to other organ systems”, said Professor Dr. Axel Haverich. Professor Schambach will also continue to be supported by REBIRTH, which is directed by MHH Professor Dr. Dr. Thomas Thum since 2019.
Professor Dr. Hildegard Büning, PD Dr. Michael Morgan, Dr. Axel Rossi, Dr. Dirk Hoffmann and Dr. Juliane Schott from the MHH Institute of Experimental Hematology have also made important contributions to the “iHEAR” project.
The cooperation with the Leibniz University Hannover is also essential for “iHEAR”, especially the researchers in the Institutes of Technical Chemistry and Organic Chemistry as well as the Center of Biomolecular Drug Research (BMWZ) who provide the small molecules and growth factors necessary for this research project.
Further information about “iHEAR” can be obtained from Professor Dr. Dr. Axel Schambach, schambach.axel@mh-hannover.de, telephone (0511) 532-5170.
Pictured in the accompanying photograph are: Professor Dr. Hildegard Büning, PD Dr. Michael Morgan, Professor Dr. Dr. Axel Schambach, Dr. Juliane Schott and PD Dr. Athanasia Warnecke (from left). You can use the photograph from this article without charges as long as you acknowledge the source as “MHH/Kaiser”.
Professor Dr. Hildegard Büning, PD Dr. Michael Morgan, Professor Dr. Dr. Axel Schambach, Dr. Juliane ...
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