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Rare Diseases and Orphan Products: Accelerating Research and Development
For example, research indicates that sickle cell trait contributes to resistance against malaria. Other genes are likely to affect susceptibility to malaria (Faik et al., 2009) and leprosy (Zhang et al., 2009).
Some rare diseases or conditions result from exposure to natural or manufactured toxic substances, including substances that appear as product contaminants. In the United States, examples include arsenic and mercury poisoning, mesothelioma (a cancer caused by exposure to asbestos), and eosinophilia-myalgia syndrome, which is associated with contaminated (or overused) tryptophan, a dietary supplement.10
It is likely that far more types of poisoning could be listed as rare conditions than are included in the list maintained by the Office of Rare Diseases Research (ORDR) at NIH. For example, the committee found newspaper reports of rare cadmium, chromium, phosphine, and other poisonings in the United States, but none is listed as a rare disease. These toxic substances are a concern of ATSDR.
Also not listed are rare poisonings caused by a variety of marine toxins that may contaminate seafood and that are tracked by the CDC (CDC, 2005). Likewise, Amatoxin poisoning, a rare and often fatal illness caused by Amanita phalloides—the “death cap” mushroom—is also not listed. Approximately 50 cases are diagnosed each year in the United States. Doctors who treat patients with this poisoning sometimes obtain FDA approval for emergency use of a milk thistle extract that is manufactured in Europe but that has not clinically evaluated or approved for marketing as a drug in the United States (Coombs, 2009).11
Some drugs have received orphan designation and approval for treatment of rare poisonings. For example, FDA has approved an orphan drug for the treatment of acute cyanide poisoning (hydroxocobalamin [Cyanokit]). Several agents have received orphan designations for treatment of snakebites, but only one has been approved (Crotalidae polyvalent immune fab [ovine] [CroFab] for certain rattlesnake and other snake bites).
Dietary supplements are regulated by FDA, but under 1994 legislation (P.L. 103-417), manufacturers are usually not required to register their products with FDA, get marketing approval based on evidence of safety and effectiveness, or report adverse events possibly related to the use of the product. FDA may take action against an unsafe supplement once it has reached the market.
The extract is, however, marketed as an herbal supplement, and a variety of unproved benefits have been asserted (NCCAM, 2008). Congress has directed that such supplements not be subjected to the same regulatory standards and review as medications.