Friday, December 28, 2007

Cortisol, Cholesterol, and Entry Inhibition

Samaritan Pharmaceuticals appears to be connecting the dots between AIDS treatment, endocrinology, immunology, and viral control.

Samaritan scientists observed correlations between cortisol levels in HIV-infected patients and the progression of their disease to AIDS. The scientists hypothesized that the HIV-associated dysregulation of cortisol levels may play a role in the pathophysiology of AIDS including the modulation of cell-mediated immunity. Experimental evidence suggested that cortisol and its receptors were critically involved at some level in the regulation of immune function in HIV infection. Therefore, it was reasonable to hypothesize that treatment with a cortisol-modulating agent may improve the immune function in HIV-infected patients.The modulatory effect of the lead compound, SP01A, on the stress-induced corticosteroid increase may be related to a reduction of the expression of the key cholesterol synthesis enzyme 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase mRNA and reduces stress-induced synthesis of steroids in vitro and in vivo, leading to a reduction in cholesterol synthesis. Many observations have suggested that inhibitors of cholesterol synthesis inhibit cell fusion formation induced by HIV-l and that drugs extracting cholesterol from the cellular membrane exert an anti-HIV-1 effect, in vitro. The unique function of SP01A is that cholesterol synthesis inhibitors exhibited the ability to exert their effect at the cellular level.Reports from the preclinical studies suggest that there is a modification of the cholesterol content of the host cell membrane due to SP01A's effect on cholesterol synthesis. This exerts a control over the replication process as the HIV-1 virus finds it difficult to enter and infect the cell. These observations were further supported during phase I/II clinical trials in which SP01A was administered to HIV-infected individuals who were currently on stable, approved antiretroviral therapies.

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