The diagnosis of inherited disorders is increasingly more complex. It is no longer sufficient to make a clinical diagnosis. We must determine the precise sequence abnormalities in order to select the appropriate therapeutic approach. Whereas currently approved pharmaceuticals target the symptoms of CF, progress must now be made in repairing the nucleotide abnormality or intervening to assist a defective protein. This will also be true in other disorders. Monogenic inherited diseases affecting widely different gene families, tissues, or enzymatic pathways reveal common themes in their disruption of cellular processes. It is increasingly more likely that progress made with one orphan disease may favorably influence therapeutic development for another, as is currently being recognized for diseases that result from protein folding or trafficking abnormalities. It has been harder to foresee that drugs developed for one purpose, such as the butyrates for excretion of waste nitrogen, also have profound effects on gene regulation and alternative enzymatic pathways in diseases such as the hemoglobinopathies, cystic fibrosis, adrenoleukodystrophy, and cancer. CF is a complex systemic inherited disorder with a wide variety of severity. The relative abundance of new compounds directed at the Class II trafficking mutation ΔF508 is encouraging and likely to benefit the majority of patients with CF. Because a single mutation can affect both protein function and location, combination therapies may be needed. Multiple approaches will almost certainly be required to control this disease.
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