Localized cell and drug delivery for auditory prostheses

Abstract

Localized cell and drug delivery to the cochlea and central auditory pathway can improve the safety and performance of implanted auditory prostheses (APs). While generally successful, these devices have a number of limitations and adverse effects including limited tonal and dynamic ranges, channel interactions, unwanted stimulation of non-auditory nerves, immune rejection, and infections including meningitis. Many of these limitations are associated with the tissue reactions to implanted auditory prosthetic devices and the gradual degeneration of the auditory system following deafness. Strategies to reduce the insertion trauma, degeneration of target neurons, fibrous and bony tissue encapsulation, and immune activation can improve the viability of tissue required for AP function as well as improve the resolution of stimulation for reduced channel interaction and improved place-pitch and level discrimination. Many pharmaceutical compounds have been identified that promote the viability of auditory tissue and prevent inflammation and infection. Cell delivery and gene therapy have provided promising results for treating hearing loss and reversing degeneration. Currently, many clinical and experimental methods can produce extremely localized and sustained drug delivery to address AP limitations. These methods provide better control over drug concentrations while eliminating the adverse effects of systemic delivery. Many of these drug delivery techniques can be integrated into modern auditory prosthetic devices to optimize the tissue response to the implanted device and reduce the risk of infection or rejection. Together, these methods and pharmaceutical agents can be used to optimize the tissue-device interface for improved AP safety and effectiveness.

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

“…However, the use of osmotic pumps to deliver neurotrophic factors clearly is not a good option for clinical application, particularly due to concerns about infection Staecker et al 2010). Numerous recent studies have explored alternative strategies for cochlear delivery of neurotrophins (Hendricks et al 2008;Richardson et al 2008), including cell-based therapies (Warnecke et al 2007;Pettingill et al 2008;Wise et al 2011), hydrogels (Endo et al 2005, and gene therapy using adenovirus-mediated expression of neurotrophic factors (Nakaizumi et al 2004;Rejali et al 2007;Chikar et al 2008;Wise et al 2010). These methods may provide better alternatives in the future, but they are still under development and concerns about potential side effects and risks have not yet been adequately addressed.…”

Vestibulo-Ocular Reflex Responses to a Multichannel Vestibular Prosthesis Incorporating a 3D Coordinate Transformation for Correction of Misalignment

“…Cochlear implant users vary widely in their ability to perceive speech (Firszt et al 2004;Zeng 2004;Wilson and Dorman 2008). Much of that variability is apparently due to differences in the survival and plasticity of neural substrates available to electrodes (e.g., cochlear nerve axons, the cochlear nucleus neurons upon which they synapse, and other brainstem and midbrain nuceli en route to auditory cortex), prompting efforts to preserve those substrates through anticipatory pharmacologic protection from ototoxic agents (Chen et al 2007); intralabyrinthine delivery of growth factors, stem cells, and gene therapy (Hendricks et al 2008); and, when no better alternative exists, prompt implantation and delivery of neuroprotective prosthetic input (Ryugo et al 2005;Stakhovskaya et al 2008).…”

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

“…150 Technically, direct delivery of pure BDNF protein is carried out by exploiting implanted osmotic minipump with drug primed cannulas that release of 0.5 or 0.25 μL/h of human recombinant BDNF. The overall dose of BDNF appeared to be important when using experimental animals with different sizes.…”