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A novel therapeutic target for OA that restores IGF-1 responses

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
93473
Program Year/Program:
2009 / SBIR
Agency Tracking Number:
AR056911
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
OMEROS CORPORATION
201 Elliott Avenue West SEATTLE, WA -
View profile »
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 2009
Title: A novel therapeutic target for OA that restores IGF-1 responses
Agency: HHS
Contract: 1R43AR056911-01
Award Amount: $148,400.00
 

Abstract:

DESCRIPTION (provided by applicant): The long-term goal of our research is to develop an effective treatment for osteoarthritis (OA). There is no effective treatment for OA, and the potential market for an OA therapy has been estimated to be 10 billion an nually. To date, efforts to develop a disease modifying drug (DMOAD) for OA have focused either on inhibiting the activity of a specific cytokine that is thought to play a pivotal role in the development of OA (e.g. IL-1), or direct inhibition of one of th e several enzymes that degrade the cartilage matrix. Very little consideration has been given to agents that stimulate matrix synthesis despite the fact that such agents could slow the progressive loss of matrix and even stimulate repair of already damaged cartilage. Although a repair response is stimulated in OA joints, recent studies show that there is a localized decrease in the expression of matrix genes in regions of focal cartilage degeneration, indicating that loss of synthetic capacity is a critical element of the degenerative process. This impaired matrix synthesis cannot be explained by insufficient levels of anabolic growth factors as there is elevated expression of IGF-1 and BMP-2 in the OA joint, particularly in the lesioned areas. The more like ly explanation is that the chondrocytes can no longer respond to these factors. Chondrocytes lose their ability to respond to IGF-1 with age, and human and monkey OA chondrocytes show a limited response to the anabolic effects of IGF-1. Therefore, any fact or that could restore growth factor sensitivity to chondrocytes would have novel therapeutic potential for the treatment of OA. Growth factor resistance can be induced in cultured chondrocytes by IL-1 and other cytokines whose expression is elevated in the OA joint. We have identified two signal transduction inhibitors, from over 80 known inhibitors that were screened, that can completely restore the IGF-1 response to IL-1 treated chondrocytes. The primary target for these two inhibitors is the same; howeve r, the fact that other inhibitors with the same specificity cannot restore the IGF-1 response indicates that a secondary target must be involved. Therefore, the objectives of this Phase I proposal are to a) identify this unique target using a siRNA knockdo wn approach, b) determine whether this target functions as a global negative modulator of IGF-1 anabolic responses and c) determine whether one of these inhibitors can stimulate repair in degenerative regions of an OA joint using a rat model of OA. PUBLIC HEALTH RELEVANCE: Currently, there is no effective treatment for osteoarthritis (OA), a severely debilitating disease that affects approximately 50% of those over 65 years of age. Our goal is to develop a novel therapeutic drug that can stimulate repair o f damaged cartilage in the OA joint.

Principal Investigator:

Emma E. Moore
2066765032
BMOORE@OMEROS.COM

Business Contact:

Gregory A. Demopulos
gdemopulos@omeros.com
Small Business Information at Submission:

OMEROS CORPORATION
1420 5TH AVE SUITE 2600 SEATTLE, WA 98101

EIN/Tax ID: 911663741
DUNS: N/A
Number of Employees: N/A
Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No