by James Cavuoto, editor
April 2014 issue
April 30, 2014 | The combination of neurostimulation devices with gene therapy offers tremendous potential for expanding the range of neurotechnology products and therapies. The interaction of the two disciplines was first demonstrated by the development of optogenetics at Stanford University in 2005. Researchers there and at other institutions have genetically modified neural cells to make them responsive to optical stimulation. The Stanford team recently demonstrated the ability to turn cells off using optogenetic techniques.
In addition, an Australian research team recently used electrical pulses delivered from a cochlear implant to deliver gene therapy, thereby successfully regrowing auditory nerves. The research, performed at the University of New South Wales, offers a new class of therapies for neurological and psychiatric disorders.
“People with cochlear implants do well with understanding speech, but their perception of pitch can be poor, so they often miss out on the joy of music,” said UNSW professor Gary Housley, senior author of a paper published in Science Translational Medicine. “Ultimately, we hope that after further research, people who depend on cochlear implant devices will be able to enjoy a broader dynamic and tonal range of sound, which is particularly important for our sense of the auditory world around us and for music appreciation.” The research, which has the support of Cochlear Ltd. through an Australian Research Council Linkage Project grant, has been five years in development.
The line of research involves regenerating surviving nerves after age-related or environmental hearing loss, using existing cochlear technology. The cochlear implants are “surprisingly efficient” at localized gene therapy in the animal model, when a few electric pulses are administered during the implant procedure.
“This research breakthrough is important because while we have had very good outcomes with our cochlear implants so far, if we can get the nerves to grow close to the electrodes and improve the connections between them, then we’ll be able to have even better outcomes in the future,” said Jim Patrick, chief scientist and senior vice-president, Cochlear Ltd.
It has long been established that auditory nerve endings regenerate if neurotrophins are delivered to the cochlea. But until now, research has stalled because safe, localized delivery can’t be achieved using drug delivery, nor by viral-based gene therapy. Housley and his team developed a way of using electrical pulses delivered from the cochlear implant to deliver the DNA to the cells close to the array of implanted electrodes. These cells then produce neurotrophins.
While neurotrophin production dropped away after a couple of months, Housley said ultimately the changes in the hearing nerve may be maintained by the ongoing neural activity generated by the cochlear implant.
“We think it’s possible that in the future this gene delivery would only add a few minutes to the implant procedure,” said the paper’s first author, Jeremy Pinyon. “The surgeon who installs the device would inject the DNA solution into the cochlea and then fire electrical impulses to trigger the DNA transfer once the implant is inserted.”
Integration of this technology into other neurotech devices such as electrode arrays used in DBS could also afford opportunities for safe, directed gene therapy of complex neurological disorders.
“Our work has implications far beyond hearing disorders,” said coauthor associate professor Matthias Klugmann, from the UNSW Translational Neuroscience Facility research team. “Gene therapy has been suggested as a treatment concept even for devastating neurological conditions and our technology provides a novel platform for safe and efficient gene transfer into tissues as delicate as the brain.”
In a paper published in Science, Karl Deisseroth’s team at Stanford showed how they were able to re-engineer light-sensitive proteins to switch cells off far more efficiently than before. “This is something we and others in the field have sought for a very long time,” said Deisseroth, senior author of the paper and professor of bioengineering and of psychiatry and behavioral sciences.
