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Thalidomide now treats a blood cancer
The scandal
Thalidomide was sold for morning sickness in Europe and many other countries before it turned out to cause birth defects. It became one of the worst medical scandals and led the FDA to change its oversight of safety for new drugs.
Cancer and the mechanism
Today it is a standard treatment for multiple myeloma, a blood cancer, and in some cases for leprosy. It works by tagging a cancer-causing protein for destruction. The same tagging and destruction happens during limb development in babies, which is how it causes birth defects.
Its side effects can be severe, and that goes together with the fact that it is reserved for a severe disease.
How does thalidomide tag proteins for destruction?
In 2010, a team led by Hiroshi Handa in Japan reported in Science that thalidomide binds a protein called cereblon. Cereblon is part of a cell's disposal machinery, which marks proteins with a chemical tag so the cell destroys them. Thalidomide changes which proteins cereblon marks, steering it toward ones it would normally ignore. Which proteins get marked differs between cell types, which is why one drug can act on cancer cells and on a developing limb.
How did thalidomide reshape US drug law?
FDA reviewer Frances Kelsey withheld approval of thalidomide in the United States in 1960 and 1961 over concerns about the safety data, so the drug was never approved for sale there. Public alarm over the European cases helped pass the Kefauver-Harris Amendments in 1962. Those amendments required manufacturers to prove that a drug is effective as well as safe before marketing it. They also required informed consent from participants in clinical trials.
How did a banned drug end up treating leprosy?
In 1964, the Israeli physician Jacob Sheskin gave thalidomide as a sedative to a leprosy patient suffering a painful inflammatory complication. The patient's symptoms eased, and later trials confirmed the effect. The drug reduces production of an inflammatory signal called tumor necrosis factor. The FDA approved thalidomide for that leprosy complication in 1998 and for multiple myeloma in 2006.
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