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A Novel Strategy to Identify Substances that Improve Mitochnodrial Fitness

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AG056253-01
Agency Tracking Number: R41AG056253
Amount: $210,672.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIA
Solicitation Number: PA16-303
Timeline
Solicitation Year: 2016
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-09-30
Award End Date (Contract End Date): 2019-08-31
Small Business Information
4230 N OAKLAND AVE #154, Shorewood, WI, 53211-2042
DUNS: 079989366
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 R HILL
 (414) 955-5885
 rbhill@mcw.edu
Business Contact
 NURAY UGRAS
Phone: (650) 473-0701
Email: ugras@pacbell.net
Research Institution
 MEDICAL COLLEGE OF WISCONSIN
 8701 WATERTOWN PLANK RD
MILWAUKEE, WI, 53226-3548
 Nonprofit college or university
Abstract
Project Summary Abstract Mitochondrial dysfunction causes mitochondrial diseases and is tightly linked to aging and neurodegenerative disorders such as Parkinsonandapos s and Alzheimerandapos s Recent discoveries support that mitochondrial dysfunction can be overcome to treat age related decline Cytegenandapos s hypothesis is that exercise induces the secretion of blood borne proteins that act systemically to stimulate removal of damaged mitochondria and enrichment of healthy mitochondria mitochondrial fitness The companyandapos s goal is to identify these proteins to develop into biologics that would serve as a platform to treat the myriad of diseases associated with mitochondrial dysfunction The discovery platform builds on existing work that exercise reversed mitochondrial dysfunction in a mouse model for mitochondrial disease Cells derived from the mutant mouse offer an attractive tool for identifying factors that improve mitochondrial fitness In this application the feasibility of a cell based assay platform is tested This platform measures colony formation mtDNA copy number mitochondrial respiration and expression of mitochondrial quality control proteins and will be evaluated in Aim using known agonists of mitochondrial biogenesis bezafibrate and the glitazones PPAR agonists metformin and AICAR AMPK and resveratrol Sirt The results will be integrated to develop a andquot fitness scoreandquot for each agonist Whether the assay platform is capable of rapidly differentiating agonistsandapos impact on mitochondrial biogenesis by their fitness score will be determined The utility of the assay platform for discovery of secreted factors will be evaluated in the second aim At least one factor identified by Cytegen to be significantly upregulated in exercised not sedentary mutant mice will be recombinantly produced and tested in the assay platform The fitness score will be compared to controls The completion of this work will identify to what extent the assay platform can be used for discovery purposes If successful this platform will help identify substances that enhance mitochondrial fitness that can be further pursued in a Phase II application for ultimate translation into clinical trials Project Narrative Mitochondrial dysfunction causes or contributes to many pathological conditions including cancer cardiomyopathies neurodegeneration aging and rare neuromuscular disorders This application proposes to evaluate exciting new technologies for discovering interventions that can restore mitochondrial function to successfully treat these diseases

* Information listed above is at the time of submission. *

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