New methods for multiple sclerosis drug discovery.
BACKGROUND
MS is a heterogeneous disorder that requires the development of better diagnostics to identify disease subtypes enabling appropriate therapeutic intervention at an early stage of the disease. Accumulating evidence indicates that members of the inhibitor of apoptosis (IAP) family play an important role in the pathogenesis of MS by reducing the apoptotic elimination of autoreactive immune cells.


METHODS
The authors describe improved animal modeling strategies to identify compounds that have immunomodulatory, neurorestorative and neuroprotective properties. In addition, the authors propose new approaches to better model cognitive dysfunction in MS, which will aid the development of novel therapeutics for this complex disorder. The paper provides the reader with an appreciation for the diagnostic and therapeutic potential of apoptosis-related proteins for MS.


CONCLUSIONS
Recent evidence suggests that increased resistance of autoreactive immune cells to apoptotic elimination is a contributing factor to both disease susceptibility and progression in MS. This occurs, at least in part, because of elevated levels of the IAP family of anti-apoptotic genes that display distinct expression profiles associated with different subtypes of MS. The authors believe that the detection and targeting of members of the IAP family can provide better drugs for MS. Particularly, the authors feel that the overexpression of IAPs in animal models can provide novel insights into MS for both its pathogenesis and the discovery of new lead compounds.
Dalhousie University ,  Department of Pharmacology ,  Halifax, NS B3H 1X5 ,  Canada.
Jordan
J
Warford
George S
GS
Robertson