A regenerative approach to the treatment of multiple sclerosis.

Progressive phases of multiple sclerosis are associated with inhibited differentiation of the progenitor cell population that generates the mature oligodendrocytes required for remyelination and disease remission. To identify selective inducers of oligodendrocyte differentiation, we performed an image-based screen for myelin basic protein (MBP) expression using primary rat optic-nerve-derived progenitor cells. Here we show that among the most effective compounds identifed was benztropine, which significantly decreases clinical severity in the experimental autoimmune encephalomyelitis (EAE) model of relapsing-remitting multiple sclerosis when administered alone or in combination with approved immunosuppressive treatments for multiple sclerosis. Evidence from a cuprizone-induced model of demyelination, in vitro and in vivo T-cell assays and EAE adoptive transfer experiments indicated that the observed efficacy of this drug results directly from an enhancement of remyelination rather than immune suppression. Pharmacological studies indicate that benztropine functions by a mechanism that involves direct antagonism of M1 and/or M3 muscarinic receptors. These studies should facilitate the development of effective new therapies for the treatment of multiple sclerosis that complement established immunosuppressive approaches.

Towards the identification of autologous blood transfusions through capillary electrophoresis.

The use of autologous blood transfusions by endurance athletes has remained one of the most difficult doping practices to detect. The implementation of the Athlete's Biological Passport by some sporting bodies has proved to be effective; however, the analysis relies on the long-term monitoring of numerous biological markers, looking for abnormal variations in a number of biological markers to indicate doping. This work introduces an approach to identify autologous blood transfusions by examining the red blood cells (RBCs) directly. By using high-speed capillary electrophoretic separations, the relative distribution of the sizes of the RBCs in a sample can be established in under 3 min, following the preparation of the cells. As RBCs that have been stored for transfusions undergo vesiculation, the relative size of the transfused cells differs from the native cells. The capillary electrophoretic separation allows for a rapid examination of this distribution and the changes that are seen when transfused RBCs are mixed with native cells. In this work, the effectiveness of this approach is demonstrated in the identification of simulated (in vitro) autologous blood transfusions performed with blood samples from three highly trained cyclists; it was possible to rapidly identify when as little as 5 % of the RBCs in the sample were from a simulated autologous transfusion.