Polymerase inhibitor in encephalomyelitis linked to immunomodulation.

2004 NOV 3 - (NewsRx.com & NewsRx.net) -- The therapeutic effects of PJ34 [N-(6-oxo-5,6dihydrophenanthridin-2-yl)-N,N-dimethylacetamide], a selective inhibitor of poly(ADP-ribose) polymerase, in experimental allergic encephalomyelitis are associated with immunomodulation.

"Poly(ADP-ribose) polymerase (PARP) activity has been implicated in the pathogenesis of several central nervous system (CNS) disorders. For example, the presence of extensive poly(ADP) ribosylation in CNS tissues from animals with experimental allergic encephalomyelitis (EAE) indicates that PARP activity may be involved in this inflammatory disease process. Using PJ34 [N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide HCl], a selective PARP inhibitor, we studied the mechanisms through which PARP activity may contribute to the onset of acute EAE," scientists writing in the United States report.

"PLSJL mice immunized with myelin antigens were treated with PJ34, and the effects on the progression of EAE and several other parameters relevant to the disease process were assessed," said Gwen S. Scott and collaborators at Thomas Jefferson University and Inotek Pharmaceuticals Corporation. "PJ34 exerted therapeutic effects at the onset of EAE that were associated with reduced CNS inflammation and the maintenance of neurovascular integrity. Expression of genes encoding the intercellular adhesion molecule-1 (ICAM-1) and the inflammatory mediators interferon-gamma, tumor necrosis factor-alpha, and inducible nitric-oxide synthase were decreased in CNS tissues from drug-treated animals."

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