Improved Auditory Nerve Survival with Nanoengineered Supraparticles for Neurotrophin Delivery into the Deafened Cochlea

by Andrew K. Wise, Justin Tan, Yajun Wang, Frank Caruso, Robert K. Shepherd

Cochlear implants electrically stimulate spiral ganglion neurons (SGNs) in order to provide speech cues to severe-profoundly deaf patients. In normal hearing cochleae the SGNs depend on endogenous neurotrophins secreted by sensory cells in the organ of Corti for survival. SGNs gradually degenerate following deafness and consequently there is considerable interest in developing clinically relevant strategies to provide exogenous neurotrophins to preserve SGN survival. The present study investigated the safety and efficacy of a drug delivery system for the cochlea using nanoengineered silica supraparticles. In the present study we delivered Brain-derived neurotrophic factor (BDNF) over a period of four weeks and evaluated SGN survival as a measure of efficacy. Supraparticles were bilaterally implanted into the basal turn of cochleae in profoundly deafened guinea pigs. One ear received BDNF-loaded supraparticles and the other ear control (unloaded) supraparticles. After one month of treatment the cochleae were examined histologically. There was significantly greater survival of SGNs in cochleae that received BDNF supraparticles compared to the contralateral control cochleae (repeated measures ANOVA, p = 0.009). SGN survival was observed over a wide extent of the cochlea. The supraparticles were well tolerated within the cochlea with a tissue response that was localised to the site of implantation in the cochlear base. Although mild, the tissue response was significantly greater in cochleae treated with BDNF supraparticles compared to the controls (repeated measures ANOVA, p = 0.003). These data support the clinical potential of this technology particularly as the supraparticles can be loaded with a variety of therapeutic drugs.

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Foxe1 Polymorphism Interacts with Dietary Iodine Intake in Differentiated Thyroid Cancer Risk in the Cuban Population

Thyroid , Vol. 0, No. 0.


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Application of Monoclonal Antibodies to Detect and Compare the Levels of Streptococcus mutans in Adolescents Undergoing Orthodontic Treatment with Those Not Undergoing Treatment

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Oct 2016, Vol. 35, No. 5: 267-271.


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Establishment of Anti-Human ATRX Monoclonal Antibody AMab-6

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Oct 2016, Vol. 35, No. 5: 254-258.


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PMab-38 Recognizes Canine Podoplanin of Squamous Cell Carcinomas

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy Oct 2016, Vol. 35, No. 5: 263-266.


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Alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 can support immune responses toward tumors overexpressing ganglioside D3 in mice

Abstract

An immunotherapeutic strategy is discussed supporting anti-tumor activity toward malignancies overexpressing ganglioside D3. GD3 can be targeted by NKT cells when derived moieties are presented in the context of CD1d. NKT cells can support anti-tumor responses by secreting inflammatory cytokines and through cytotoxicity toward CD1d⁺GD3⁺ tumors. To overexpress GD3, we generated expression vector DNA and an adenoviral vector encoding the enzyme responsible for generating GD3 from its ubiquitous precursor GM3. We show that DNA encoding α-N-acetyl-neuraminide α-2,8-sialyltransferase 1 (SIAT8) introduced by gene gun vaccination in vivo leads to overexpression of GD3 and delays tumor growth. Delayed tumor growth is dependent on CD1d expression by host immune cells, as shown in experiments engaging CD1d knockout mice. A trend toward greater NKT cell populations among tumor-infiltrating lymphocytes is associated with SIAT8 vaccination. A single adenoviral vaccination introduces anti-tumor activity similarly to repeated vaccination with naked DNA. Here, greater NKT tumor infiltrates were accompanied by marked overexpression of IL-17 in the tumor, later switching to IL-4. Our results suggest that a single intramuscular adenoviral vaccination introduces overexpression of GD3 by antigen-presenting cells at the injection site, recruiting NKT cells that provide an inflammatory anti-tumor environment. We propose adenoviral SIAT8 (AdV-SIAT8) can slow the growth of GD3 expressing tumors in patients.

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Post-Finasteride Syndrome Not Related to Androgen Deficiency

Men who report persistent sexual symptoms after using finasteride for hair loss do not show abnormalities in androgens or their receptors, according to a new report.
Reuters Health Information

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