Round Window Membrane Delivery of NGF (Nerve Growth Factor) for Spiral Ganglion Cells Survival

Discussion in 'Research News' started by Arseny, Apr 12, 2019.

    1. Arseny
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      Arseny Member

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      A very interesting read, but unless you have an access to a lab it's unrealistic and seems that you need continuous supplementation of NGF to ensure spiral ganglion survival.

      I wonder how can you boost growth factors via medication or supplements.

      https://www.dovepress.com/enhanced-...riol-lipid-peer-reviewed-fulltext-article-IJN

      Purpose: Supplementation of exogenous nerve growth factor (NGF) into the cochlea of deafened animals rescues spiral ganglion cells from degeneration. However, a safe and potent delivery of therapeutic proteins, such as NGF, to spiral ganglion cells remains one of the greatest challenges. This study presents the development of self-assembled cubic lipid-based crystalline nanoparticles to enhance inner ear bioavailability of bioactive NGF via a round window membrane route.

      Methods: A novel nanocarrier-entrapped NGF was developed based on phytantriol by a liquid precursor dilution, with Pluronic® F127 and propylene glycol as the surfactant and solubilizer, respectively. Upon dilution of the liquid lipid precursors, monodispersed submicron-sized particles with a slight negative charge formed spontaneously.

      Results: Biological activity of entrapped NGF was assessed using pheochromocytoma cells with NGF-loaded reservoirs to induce significant neuronal outgrowth, similar to that seen in free NGF-treated controls. Finally, a 3.28-fold increase in inner ear bioavailability was observed after administration of phytantriol lipid-based crystalline nanoparticles as compared to free drug, contributing to an enhanced drug permeability of the round window membrane.

      Conclusion: Data presented here demonstrate the potential of lipid-based crystalline nanoparticles to improve the outcomes of patients bearing cochlear implants.
       
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    2. Contrast
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      This could be used for the treatment of hidden hearing loss as well, at least to hopefully preserve hearing.

      Charlie Liberman's research showed use of NT-3 to regrow cochlear ribbon synapses in a short term window after the mice were exposed to noise.
      https://www.nature.com/articles/srep24907
       
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      Arseny
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      Arseny Member

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      Have you seen this?
      https://patents.google.com/patent/US20190022101A1/en

      Methods of treating or reducing the risk of developing hidden hearing loss by administering a small molecule Trk agonists (e.g., amitriptyline, imipramine, LM 22A4 (N,N′,N″Tris(2-hydroxyethyl)-1,3,5-benzenetricarboxamide), 7, 8-dihydroxyflavone (DHF), 7,8,3′-Trihydroxyflavone (THF), Mab2256, neurotrophin-4 (NT-4), neurotrophin-3 (NT-3), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF), N-acetylserotonin, N-[2-(5-Hydroxy-1H-indol-3-yl)ethyl]-2-oxo-3-piperidinecarboxamide (HIOC), deoxygedunin, LM-22A4, or tricyclic dimeric peptide 6 (TDP6)).

      It also funded by Department of Defense.
      • FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
      • [0002]
        This invention was made with Government support under Grant Nos. RO1 DC08577, RO1 DC007174, RO1 DC0188, P30 DC05209, awarded by the National Institutes of Health and Grant No. W81XWH-15-0103 awarded by the Department of Defense. The Government has certain rights in the invention.
       
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    4. Contrast
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      Contrast Member Benefactor Hall of Fame

      Location:
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      I barely understand any of this stuff. I'm such a layman, all I know is that very loud noise causes ribbon synapses in the cochlea die before the hair cells, and it causes music to be ruined and trouble hearing in background noise if it gets bad enough. The good part is because the spiral ganglion cells take forever to die there's still hope for therapeutic effect with NT-3 and other things.

      I'm glad this is being researched.
       
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