Browsing by Author "Rachael, Richardson"

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    New molecular therapies for the treatment of hearing loss
    (Elsevier, Inc., 2019-05) Ma, Yutian; Wise, Andrew; Shepherd, Robert; Rachael, Richardson
    An estimated 466 million people suffer from hearing loss worldwide. Sensorineural hearing loss is characterized by degeneration of key structures of the sensory pathway in the cochlea such as the sensory hair cells, the primary auditory neurons and their synaptic connection to the hair cells - the ribbon synapse. Various strategies to protect or regenerate these sensory cells and structures are the subject of intensive research. Yet despite recent advances in our understandings of the capacity of the cochlea for repair and regeneration there are currently no pharmacological or biological interventions for hearing loss. Current research focusses on localized cochlear drug, gene and cell-based therapies. One of the more promising drug-based therapies is based on neurotrophic factors for the repair of the ribbon synapse after noise exposure, as well as preventing loss of primary auditory neurons and regrowth of the auditory neuron fibers after severe hearing loss. Drug therapy delivery technologies are being employed to address the specific needs of neurotrophin and other therapies for hearing loss that include the need for high doses, long-term delivery, localised or cell-specific targeting and techniques for their safe and efficacious delivery to the cochlea. Novel biomaterials are enabling high payloads of drugs to be administered to the cochlea with subsequent slow-release properties that are proving to be beneficial for treating hearing loss. In parallel, new gene therapy technologies are addressing the need for cell specificity and high efficacy for the treatment of both genetic and acquired hearing loss with promising reports of hearing recovery. Some biomaterials and cell therapies are being used in conjunction with the cochlear implant ensuring therapeutic benefit to the primary neurons during electrical stimulation. This review will introduce the auditory system, hearing loss and the potential for repair and regeneration in the cochlea. Drug delivery to the cochlea will then be reviewed, with a focus on new biomaterials, gene therapy technologies, cell therapy and the use of the cochlear implant as a vehicle for drug delivery. With the current pre-clinical research effort into therapies for hearing loss, including clinical trials for gene therapy, the future for the treatment for hearing loss is looking bright.
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    Optical stimulation of neural tissue
    (IET, 2020-07) Rachael, Richardson; Ibbotson, Michael; Thompson, Alexander; Wise, Andrew; Fallon, James
    Electrical stimulation has been used for decades in devices such as pacemakers, cochlear implants and more recently for deep brain and retinal stimulation and electroceutical treatment of disease. However, current spread from the electrodes limits the precision of neural activation, leading to a low quality therapeutic outcome or undesired side-effects. Alternative methods of neural stimulation such as optical stimulation offer the potential to deliver higher spatial resolution of neural activation. Direct optical stimulation is possible with infrared light, while visible light can be used to activate neurons if the neural tissue is genetically modified with a light sensitive ion channel. Experimentally, both methods have resulted in highly precise stimulation with little spread of activation at least in the cochlea, each with advantages and disadvantages. Infrared neural stimulation does not require modification of the neural tissue, but has very high power requirements. Optogenetics can achieve precision of activation with lower power, but only in conjunction with targeted insertion of a light sensitive ion channel into the nervous system via gene therapy. This review will examine the advantages and limitations of optical stimulation of neural tissue, using the cochlea as an exemplary model and recent developments for retinal and deep brain stimulation.