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Novel Theranostic Approaches to Identify and Treat Tinnitus Using Functionalized Nanoparticles

Award Number: R21DC013895
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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DESCRIPTION (provided by applicant): In the United States, about 50 million individuals suffer from tinnitus (perception of sound without overt acoustic stimulation), with circa 3 million people that are disabled and require treatment. Unfortunately, current treatment options for tinnitus are often ineffective and produce inconsistent and sometimes disappointing results. New and innovative approaches for diagnosis and treatment of tinnitus are urgently needed. Here, we introduce a novel concept for tinnitus research and abatement based on the hypothesis that over-expression of genes within brain regions with hyperactive neuronal activity associated with tinnitus can be identified and targeted using multifunctional capsid-based nanoparticles. The effort proposed here leverage a multifunctional capsid-based nanoparticle platform and represents the initial step toward our long-term goal to establish a nanoparticle-based platform to localize and treat tinnitus by attenuating hyperactive neural activity. We will ) evaluate whether nanoparticles can localize to specific targets in vitro and in vivo and ii) optimize the design for ideal localization within the brain and transport across the blood-brain-barrier (BBB) with negligible side effects. Here we seek to evaluate the feasibility of using nanoparticles for in vivo use and establish a solid foundation where future work will enable more in-depth studies using animal models of tinnitus. Specific Aim 1. To establish targeting of specific proteins within the inferior colliculus (IC) using custom-fabricated nanoparticles. Nanoparticles (NPs) will be designed to target proteins demonstrated to be differentially expressed in areas with tinnitus related hyperactivity. Adult Sprague-Dawley rats will be used to evaluate targeting specificity of the NPs. NPs decorated with antibodies that bind receptors in active neurons and loaded with fluorophore will be used for visualization during histological assessment. Two approaches to validate the specificity of NP binding are used: 1. Western blotting will be used to establish that the NPs are capable of binding the protein-of-interest isolated from the IC. This assessment will include, exposure to i) NPs modified with the specific antibody, ii) NPs without the antibody and iii) antibody alone. 2. Microscopy will be used to verify NP binding to the protein of interest in native IC cells. NPs loaded with a fluorescent tag will be localized to quantify differences in NP distribution within and across i) specific subdivisions of the IC ii) other auditory brain regions, as well as, iii) non-auditory brain region. Specific Aim 2. To optimize dose, localization, and transport of MRI detectable custom fabricated nanoparticles across the BBB. Adult Sprague-Dawley rats will be given a systemic injection of custom- designed NPs. They will be modified with a short peptide that facilitates BBB transport (through LPR-1). At multiple time points following injection, nanoparticles with a paramagnetic core and a conjugated fluorescent tag, will be localized: 1. with T1-weighted MRI and 2. cross-validated by fluorescence-based microscopy using frozen sections.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = -$1,663 )
2018	2016	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	257 FULLER RD	ALBANY	NY	12203	ALBANY	USA	Research Related to Deafness and Communication Disorders	000	3	3/7/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,663
														Subtotal = -$1,663

Issue Date FY: 2016 ( Subtotal = $182,172 )
2016	2016	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Research Related to Deafness and Communication Disorders	000	2	11/12/2015	NON-COMPETING CONTINUATION	$163,954
2016	2016	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Research Related to Deafness and Communication Disorders	001	2	1/8/2016	NON-COMPETING CONTINUATION	$18,218
2016	2016	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Research Related to Deafness and Communication Disorders	002	3	8/1/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$137,511
2016	2016	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Research Related to Deafness and Communication Disorders	003	2	8/1/2016	NON-COMPETING CONTINUATION	-$137,511
														Subtotal = $182,172

Issue Date FY: 2015 ( Subtotal = $233,672 )
2015	2015	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Research Related to Deafness and Communication Disorders	000	1	12/1/2014	NEW	$233,672
														Subtotal = $233,672

Grand Total All Awards = $414,181

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Novel Theranostic Approaches to Identify and Treat Tinnitus Using Functionalized Nanoparticles

Award Number: R21DC013895

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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