lecture 22 Flashcards
(16 cards)
what is an issue in profound hearing loss?
Cell loss and cell atrophy of SGN
The ones that remain seem to be healthy
What is a potential solution to this gradual loss of nerve supply to the cochlea?
Neurotrophins
What are neurotrophins
Growth factor proteins important for neuron health released by cells in the sensory epithelium
why is there a natural loss in endogenous neurotrophins in those with profound hearing loss
the sensory epithelium gets degenerated, hence reduction in Endogenous Neurotrophin
What do neurotrophins do specifically?
Promote complete nerve survival
Protect Spiral ganglion neurons
Promote fibre regrowth
Reduce electrical thresholds
mini pump administration and the concerns
mini pump delivers neurotrophins into the scala tympani, bathing the nerve population
- safety concerns?
- long term viability?
- significant limitations to this approach
different delivery methods of neurotrophins
“smart” polymers
Cell based therepies
Neurotrophin gene therepy
Nanoengineered particles
describe the smart polymer method of neurotrophin delivery
Polymers loaded with therapeutic drugs –>
coat the electrode contacts of CI with polymer –> stimulate the device, growth factor released
- has limitations
describe the cell based therepy method of neurotrophin delivery
capsules made from alginate with cells inside that naturally produce and release neurotrophin. I
Inserted with the cochlea implant
describe the neurotrophin gene therepy method of neurotrophin delivery
Microelectrode into the scala media compartment –> released the viral vector that went on to transfect certain cells in the scala media
what were the results of neurotrophin gene therepy
Significant spiral ganglion neuron protection and survival
Role in fibre regrowth around neurotriphic producing cells
Describe the nanaoengineered particles method of neurotrophin delivery
large particles developed comprised of millions of small particles. (released slowly over 2-3 months)
surgical implantation of particles intracochlear delivery (basal turn)
what were the results of nano-engineered particle delivery
- large neurotrophin payload
- widespread effects throughout cochlea
- effective over long term
- biologically compatible
why has neurotrophin treatment not been successfully translated to the clinic
difficulty in safely delivering these delicate molecules into the inner ear over time in a way that maintains bioactivity.
what happens after loud noise exposure for someone with normal hearing
loss of OHC function temporarily
“stnaptopathy” loss of synaptic connections
what is a potential delivery avenue of neurotrophins that wouldn’t result in hearing loss?
round window delivery
