High cholesterol and its link to heart disease is a common topic in the media. But for the 2,000 to 3,000 Americans with homozygous familial hypercholesterolemia (FH) the phrase "high cholesterol" takes on a whole new meaning. FH patients have five- to ten-fold more low density lipoprotein (LDL), the "bad" cholesterol, than the general public. Without therapy, they develop heart disease and are at risk for death as young adults.
When Daniel J. Rader, MD, started working on FH, the only effective treatment for patients was to physically remove LDL from their blood via apheresis. And they had to undergo the time consuming, invasive process every week or two.
Rader, though, had an ah-ha moment when studying abetalipoproteinemia, an inherited disease in which patients have virtually no LDL. He was part of a team that discovered the gene responsible for abetalipoproteinemia, the microsomal triglyceride transfer protein (MTP) gene. Without a normal copy of the gene, the livers of these patients cannot make LDL.
Rader flipped that insight upside down and reasoned that blocking the MTP protein with a drug might reduce LDL in patients with FH. After a winding road that included negotiating with a major pharmaceutical company, clinical trials, and finding ways to deal with serious toxicities, Rader's team gained US Food and Drug Administration approval for a new pill, called lomitapide, in December 2012 for patients with FH.