During the last decade, a rich and active program of collaboration has developed between the Miller Laboratory at the KHRI, Dr. Colleen Le Prell (Univeristy of Florida) and laboratories in Sweden (Karolinska Institute and University of Uppsala), Finland (Turku University and University of Tampere), Germany (Hannover Medical University), Austria (University of Innsbruck), Australia (Melborne University), Japan (Kanzai University and Tokyo University) and Spain (Universidad de Castilla La Mancha). These collaborations include three main emphases:
- Tissue engineering to promote auditory nerve regrowth following deafness
- Prevention of noise-induced hearing loss
- Improving the outcomes of cochlear prosthesis implantation
These collaborations are facilitated by student fellowships and frequent investigator travel for targeted research projects.
Tissue Engineering to Promote Auditory Nerve Regrowth Following Deafness
One model program reflecting these collaborations is focused on the translation of basic research observations on the mechanisms of cell survival and death following deafferentation to interventions that can be administered to promote auditory nerve survival and regrowth in the deaf patient receiving a cochlear implant. This program now involves a number of studies to bring our basic animal studies to the point of human clinical trials. These studies include:
- In vitro studies of human auditory nerves to evaluate responsiveness to neurotrophins found effective in animal studies and identification of precursor cells in the human temporal bone (Uppsala University; H. Rask-Andersen)
- Immunohistochemistry studies to identify the Trk receptors on human spiral ganglion cell that will be receptive to neurotrophin treatment (B)
- In-vivo animal studies to evaluate the effectiveness of delayed neurotrophin and antioxidant treatment on nerve survival, to better model the human situation (Karolinska Institute; M. Ulfendahl)
- In vivo animal investigation to evaluate the interactive effectiveness of antioxidants, electrical stimulation, and neurotrophins in promoting cell survival and regrowth of the auditory nerve (University of Michigan; J. Miller, R. Altschuler, Y. Raphael)
- In vivo animal studies to evaluate the interaction of electrical stimulation and neurotrophins on auditory nerve cell survival and the up-regulation of neurotrophins and their receptors in this tissue with deafness and treatment (Hannover Medical University; T. Stover, T. Lenarz)
- Development of human implants capable of short term chronic delivery of neurotrophins and antioxidants to the inner ear (Med-El Corp., Innsbruck)
- Toxicity studies of neurotrophins on the neural tissues of the inner ear (University of Michigan, J. Miller)
Together these studies provide the experimental rationale to permit preliminary human clinical trials in implanted patients.
Prevention of Noise-induced Hearing Loss
A second major program with significant international cooperation is our program focused on the prevention of noise-induced hearing loss. These studies include:
- In vivo animal studies to evaluate the synergistic effects of antioxidants and other dietary supplements used to prevent noise induced hearing loss associated with exposure to chronic noise (University of Michigan; J. Miller, University of Florida; C. Le Prell; Washington University: K. Ohlemiller)
- In vivo animal studies to evaluate the synergistic effects of antioxidants and other dietary supplements used to prevent noise induced hearing loss associated with exposure to impulse noise (Karolinska Institute; M. Duan, G. Laurell)
- Human clinical trials to evaluate the effectiveness of antioxidants and other dietary supplements used to prevent noise-induced hearing loss as a consequence of impulse noise exposure during military training exercises (Karolinska Institute; U. Rosenhall, P.-A. Hellstrom, B. Hagerman, A.-C. Lindblad)
- Human clinical trials to evaluate the effectiveness of antioxidants and other dietary supplements used to prevent noise-induced hearing loss as a consequence of occupational noise exposure in NATO airbase personnel and workers in the cutlery industry(Universidad de Castilla La Mancha; J. Juiz)
- Human clinical trials for evaluation of the effectiveness of antioxidants and other dietary supplements in prevention of temporary noise-induced hearing loss as occurs with use of insert earphones and personal music players(University of Florida; C.Le Prell, J.Hall III; P. Antonelli)
- Toxicity studies of novel antioxidants, and novel combinations of antioxidants and other dietary supplements, on the neural tissues of the inner ear (University of Michigan; J. Miller)
Our U.S. partners in all of the above human trials are Drs. Kathleen Campbell (Southern Illinois University School of Medicine) and Sharon Kujawa (Harvard University). Together, these studies will document the efficacy of a treatment to prevent noise-induced hearing loss in humans exposed to traumatic levels of sound as a consequence of recreational and/or occupational activities.
BioEar: Improving the Outcomes of Cochlear Prosthesis Implantation
Dr. Miller is the scientific director of an E.U. funded consortium working to improve the performance of the cochlear prosthesis. Thus, the studies described in this section reflect work performed not only in the Tissue Engineering Laboratory at the KHRI but also substantial efforts by an international consortium of academic and industrial partners. Academic partners include the Karolinska Institutet, Sweden, (Drs. Ulfendahl and Järlebark), University Of Hannover, Germany, (Drs. Lenarz, Stöver, and Reuter), University of Ferrara, Italy (Dr. Martini, and Maurizio Previati, MS), Uppsala University, Sweden (Dr. Rask-Andersen), the University of Insbruck, Austria (Dr. Schrott-Fischer), University of Tampere, Finland (Dr. Pyykkö) and Tampere University of Technology, Finland (Dr. Minna Kellomaki). Industrial partners include MED EL Elektromedizinische Geräte (Innsbruck, Austria), and BCI Bioabsorbable Concepts Ltd., (Tampere, Finland).
The cochlear implant (CI) has been the "success story" of neuroprosthetic devices. The development of this device, in the last 25 years, initially provided profoundly deaf patients with their first contact with the world of sound. With improvements in cochlear research technology have come progressive improvements in speech discrimination by implant users, and now substantial open-set (auditory only) speech discrimination achievable by the majority of implant patients. With continued development of signal processing strategies and electrode technology, the benefits to the deaf patient may yet increase, however it appears likely that present technology is optimized, and further progress limited by the status of the deprived auditory system itself.
There is still a large potential for improvement in cochlear implant outcomes. The major goal of this program is to improve the outcomes of cochlear implantation using drug application at the time of implantation. This could be achieved by preventing neural degeneration during the traumatic procedure of implantation and initiating a re-growth of the peripheral processes of the auditory nerve towards the electrode array. Longer term goals are to:
- better understand the role of growth factors and other agents in preventing neural degeneration,
- look towards the opportunity to provide these agents in patients with moderate hearing impairment to prevent its progress, and
- provide data that may make the use of these agents practical in other parts of the central nervous system (CNS)
The work therefore represents a scientific turning point, which has the potential to lead to immense future benefits for the community.
The immediate goal of the BioEar consortium is micro-fluidic drug-delivery in association with cochlear prosthesis implantation. Future generation drug delivery techniques will include biopolymer molecules coating the prosthesis and allowing slow delivery of drugs (such as growth factors or other agents), genes (for upregulating endogenous production of growth factors or other agents), or cells, into the deaf cochlea.