INDOLEAMINE 2,3-DIOXYGENASE IN OPPORTUNISTIC INFECTIONS

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$50,000.00
Award Year:
1992
Program:
SBIR
Phase:
Phase I
Contract:
n/a
Award Id:
18977
Agency Tracking Number:
18977
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
4100 South Kettering Blvd, Dayton, OH, 45439
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
Wei Dai
(513) 293-8508
Business Contact:
() -
Research Institute:
n/a
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.

* information listed above is at the time of submission.

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