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Effects of OX2R agonist and antagonist on sleep apnea

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
Program Year/Program:
2011 / STTR
Agency Tracking Number:
R41HL107037
Solicitation Year:
2011
Solicitation Topic Code:
NHLBI
Solicitation Number:
PA10-051
Small Business Information
BIOFUNC RESEARCH
4775 WESTMINSTER LN BROADVIEW HEIGHTS, OH 44147-
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2011
Title: Effects of OX2R agonist and antagonist on sleep apnea
Agency: HHS
Contract: 1R41HL107037-01A1
Award Amount: $159,108.00
 

Abstract:

DESCRIPTION (provided by applicant): The long term goal of this project is to develop and commercialize a drug to treat sleep apnea. Sleep apnea is a common medical condition and associated with excessive daytime sleepiness and is a composite risk for cardiovascular morbidity and mortality. Presently, there are no effective pharmacotherapies for individuals with sleep apnea. Growing evidence from both clinical and basic research is quickly approaching the concept that alterations of orexins play a role in the pathology of sleep apnea. Basic research has shown that orexins are directly involved in respiratory control, and a lower level of brain orexins accompanies the frequent appearance of ventilationary pauses. This evidence supports the further study of the direct effects of orexin receptor agonists and antagonists on ventilation; it also suggests that a cell assay should be created to pave the way for the development of a pharmaceutical treatment of sleep apnea. This project will determine the effects oforexin-2 receptor (OX2R) agonists and antagonists on the occurrence of sleep apnea in a mouse model, and it will optimize an established cell-based assay of an OX2R cell line. The hypothesis is that OX2R agonists prevent the occurrence of sleep apnea, andOX2R antagonists produce apnea. The project will measure ventilation rhythm by the plethysmography method combined with sleep recording in the mouse model. Animals will be treated with OX2R agonists or agonists plus antagonists or a control agent, such asartificial corticospinal fluid, via intracerebroventricular injection. A sleep apnea-hypopnea index (AHI) will be calculated for a daily 8 hours of recording data. Comparisons between the baseline and the treatment periods as well as among treatment groupswill be evaluated. Optimizing OX2R cell-based assay is the secondary study in this project. Using a cell culture method and a commercially available cell-based assay kit, the project will measure optimal cell response to the OX2R agonist and antagonist treatment. Successful completion of this project will either confirm or refute the hypothesis that OX2R agonists prevent sleep apnea; additionally, it will create a cell line-based assay for the future development of drugs that may eventually lead to effective pharmacotherapy for sleep apnea. PUBLIC HEALTH RELEVANCE: This project will evaluate the potential therapeutic effect of endogenous orexin receptor agonists on sleep apnea in a mouse model and optimize a established cell-based assay for further development in this new direction. Successful completion of this project will establish a strong and solid foundation for the Phase II development of lead compound research in the pharmaceutical treatment of sleep apnea.

Principal Investigator:

Pingfu Feng
216-791-3800
dxpfeng@gmail.com

Business Contact:

Pingfu Feng
440-391-8028
dxpfeng@gmail.com
Small Business Information at Submission:

BIOFUNC RESEARCH
4775 WESTMINSTER LN BROADVIEW HEIGHTS, OH 44147-

EIN/Tax ID: 180035164
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
Research Institution Information:
CASE WESTERN UNIVERSITY
CASE WESTERN RESERVE UNIVERSITY
10900 EUCLID AVE
CLEVELAND, OH 44106-7015
Contact: