PALOMA PHARMA 529 TREATMENT FOR SIV STUDY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Palomid 529 (P529), is a synthetic small molecule drug that inhibits a cellular pathway involved in signaling to regulate translation. When this pathway is aberrantly activated, it can lead to a variety of pathological conditions including cancer, ocular and skin diseases and can promote viral replication. P529 inhibits the aberrant activation of this pathway and has shown activity when tested in animal models of cancer and ocular diseases. P529 was tested in vitro in SIV infected cell cultures. Cell cultures pre-treated with 25uM or 250uM Palomid showed anti-viral activity. Lower dose were negative. Based on promising in vitro results, two SIVmac251 infected, Indianorigin rhesus macaques were treated with 12 mg/kg P529 for five consecutive days. The animals were then allowed to rest, untreated, for nine days. After this rest period, the animals were treated with 24 mg/kg P529 for five consecutive days. Blood samples were collected to monitor plasma virus load levels, in vivo drug concentrations and basic blood parameters for any toxicity. No decreases in plasma virus load were observed at either dose.