Figure 2.

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