MS is an inflammatory disease of the CNS with a complex etiology. It is believed that macrophages and microglia cells play a key role in the progression of the diseases. In this research project, we have used novel ligands for the peripheral benzodiazepine receptors (PBR), which are expressed in activated macrophages and microglia, for the early detection of these cells in two animal models of neuroinflammation (Experimental Autoimmune Encephalomyelitis (EAE) and cuprizone demyelination). Since PBR receptors as well appear to be able to modulate cell death, we will also use our novel ligands in attempts to treat the two animal models mentioned.
We have performed several imaging studies using EAE in rats. Our results were satisfactory in regard to in vitro and ex vivo studies, showing that our leading compound (CLINDE) was suitable for the detection of neuroinflammation. Moreover, our preliminary in vivo studies demonstrate that CLINDE is suitable for detecting neuroinflammation in the cuprizone model of demyelination. These results clearly show a potential in vivo application for the clinical use of CLINDE and its derivates in the detection of inflammatory cells in the CNS. Finally, we have undertaken several experiments aimed to evaluate the anti-inflammatory properties of our novel PBR ligands. From our results, it can be concluded that some PBR ligands are able to modulate several macrophage functions, suggesting that the use of these compounds may represent a reasonable alternative for the treatment of some forms of neuroinflammation.
The results derived from this investigation will help in the improvement of the MS diagnosis and management and also in the development of new therapies focused on the suppression of the pathological mechanisms of MS.
Updated: 05 January, 2006