Figure 2

Only a few specific loss-of-function genetic diseases match the concept of apharmaceutical target. Although the concept of a pharmaceutical targetdoes not fit most loss-of-function diseases, channelopathies and some metabolicdiseases are exceptions to the rule. A) Schematic view of putative strategiesto treat a partial loss-of-function affecting an ion channel. Agonists maystimulate the channel to increase its activity. Alternatively, antagonists ofopposite-effect channels may restore the ion balance of the cell. B) Schematicview of putative strategies to treat a loss-of-function disease affecting anenzyme. In this example, the reduction of enzyme activity (blue cross) resultsin a deficit in a key metabolite A. This deficit may be compensated byinhibiting A-transforming enzymes (1), increasing the abundance of a precursor(2), and stimulating A-producing enzymes (3). (Supplementation of A, also atherapeutic possibility for some disorders, is not shown.)