EXCEED THE SPACE PROVIDED. HIV-associated dementia (HAD) involves destruction of neurons and synapses. Brain inflammatory cells, including brain microglia and invading blood monocytes, participate in this CNS-damaging pathway by release of neurotoxins. We have identified drugs that are highly protective against inflammatory cell- mediated neuron injury. Some of these agents are also able to reduce brain inflammation in the HIV/AIDS volunteers. This fast track SBIR proposal seeks to develop a new drug formulation with neuroprotective effects against CMS injury in HIV/AIDS. In Phase I, we will optimize pharmaceutical properties of a new formulation in vitro, establish an effective dosing schedule for neuroprotection in man, and determine pharmacokinetic profiles in human volunteers. The goal of Phase 2 will be to advance the new drug formulation into a clinical trial using HIV/AIDS volunteers. A 12-week double-blinded, placebo controlled study will determine the ability of the new drug formulation to alter a biomarker of brain inflammation and to improve cognition during the treatment period. PERFORMANCE SITE ========================================Section End===========================================
