Atypical HUS & Orphan Drugs

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Atypical HUS refers to hemolytic uremic syndrome which occurs without E. coli 0157:H7-induced diarrhea as the inciting event. There are many causes of atypical HUS: calcineurin inhibitors, HIV, pneumococcal infection and rare genetic diseases are all on the differential diagnosis. On this latter point (genetic diseases), about 50% of all cases of atypical HUS are caused by mutations in genes which are involved in the complement cascade: specifically, the factor H, factor I, and MCP genes.
Individuals with complement-associated atypical HUS have a relatively high degree of renal problems, and unfortunately there are few therapies other than standard supportive measures which can be used to help treat it. One obvious strategy for treating this disease would be to target the complement cascade. Enter eculizumab (trade name Solaris), a monoclonal antibody against the complement protein C5 (which if you’ll recall your complement cascade is at the nexus of both alternative and classical pathways). Already approved for the treatment of other disorders of complement dysregulation (specifically: paroxysmal nocturnal hemoglobinuria), eculizumab was recently granted “orphan status” in an attempt to aid its testing in clinical trials for patients with atypical HUS.

What does “orphan status” mean, exactly? The Orphan Drug Act of 1983 was passed in order to encourage the development of drugs for diseases with a small market, defined as affecting less than 200,000 total individuals in the U.S. The act gives pharmaceutical companies enough incentive to invest in developing drugs for treating rare diseases via granting a prolonged competition-free period and clinical trial tax breaks. There are several nephrology-related diseases which would fall into this category.

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