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INDOLEAMINE 2,3-DIOXYGENASE IN OPPORTUNISTIC INFECTIONS

Award Information

Agency:
Department of Health and Human Services
Branch:
N/A
Award ID:
18977
Program Year/Program:
1992 / SBIR
Agency Tracking Number:
18977
Solicitation Year:
N/A
Solicitation Topic Code:
N/A
Solicitation Number:
N/A
Small Business Information
Hipple Cancer Research
4100 S Kettering Boulevard Dayton, OH 45439
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Woman-Owned: No
Minority-Owned: No
HUBZone-Owned: No
 
Phase 1
Fiscal Year: 1992
Title: INDOLEAMINE 2,3-DIOXYGENASE IN OPPORTUNISTIC INFECTIONS
Agency: HHS
Contract: N/A
Award Amount: $50,000.00
 

Abstract:

CENTRAL NERVOUS SYSTEM TOXOPLASMOSIS HAS CAUSED DISABILITY AND DEATH IN UP TO 30% OF PATIENTS WITH AIDS. CURRENT CLINICAL TREATMENT FOR TOXOPLASMA INFECTION IS MAINLY CHEMOTHERAPEUTICAL, WHICH IS OFTEN ASSOCIATED WITH DOSE-RELATED BONE MARROW SUPPRESSION. COMPLETE REMISSION OF THE INFECTION DEPENDS LARGELY ON THE ADEQUATE RESTORATION OF THE CELL-MEDIATED IMMUNE SYSTEM OF THE PATIENTS AND THUS, IT POSES A CONTINUOUS THREAT TO AIDS PATIENTS. AN ALTERNATIVE TREATMENT USING RECOMBINANT INTERFERON-GAMMA (IFN-GAMMA) HAS BEEN PROPOSED SINCE IFN-GAMMA, A CD4+T CELL PRODUCT, BLOCKS THE GROWTH OF T GONDII IN A VARIETY OF TISSUES AND CELLS. THIS IFN-GAMMA-MEDIATE ANTI-TOXOPLASMIC ACTIVITY IS STRONGLY CORRELATED WITH THE DEGRADATION OF THE ESSENTIAL AMINO ACID L-TRYPTOPHAN IN VITRO. DESTRUCTION L-TRYPTOPHAN IS DUE TO THE INCREASED ACTIVITY OF INDOLEAMINE 2,3 DIOXYGENASE (ISO) WHICH IS IN TURN TRANSCRIPTIONALLY ACTIVATED BY IFN-GAMMA. IT HAS BEEN SUGGESTED THAT T GONDII INFECTION IS PRIMARILY CONTROLLED BY IDO ACTIVITY INDUCED BY IFN-GAMMA DERIVED FROM CD4+ T LYMPHOCYTES. THEREFORE, WE WILL INVESTIGATE THE ROLE OF IDO IN HOST DEFENSE AGAINST T GONDII INFECTION, AND SPECIFICALLY TO DETERMINE WHETHER IDO ACTIVITY ALONE, EXPRESSED VIA STABLE TRANSFECTION OF IDO CDNA CONTROLLED BY A METALLOTHIONEIN INDUCIBLE PROMOTER, BLOCKS THE GROWTH OF T GONDII IN CULTURED HUMAN FIBROBLASTS AND MACROPHAGE CELL LINE. ELUCIDATION OF THE ROLE OF IDO IN BLOCKING T GONDII REPLICATION WILL PROVIDE NOT ONLY HOST DEFENSE MECHANISM BUT ALO NEW CONCEPT FOR DEVELOPING EFFECTIVE DRUGS FOR PREVENTION AND TREATMENT OF TOXOPLASMOSIS IN AIDS PATIENTS.

Principal Investigator:

Wei Dai
5132938508

Business Contact:

Small Business Information at Submission:

Hipple Cancer Research Center
4100 South Kettering Blvd Dayton, OH 45439

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