A recent FDA advisory panel recommended the approval of 2 new agents in a novel class of cholesterol lowering drugs known as PCSK-9 inhibitors. What makes this remarkable is that these drugs illustrate all the promise and pitfalls of modern pharmaceutical development.
First, a little science. The target of the new drugs – a protein named proprotein convertase subtilisin/kexin type 9 (PCSK-9) – was discovered in 2001. Two years later, investigators reported that “gain-of-function” mutations in the gene that codes for PCSK-9 were associated with familial hypercholesterolemia and high rates of atherosclerotic vascular disease. Mutations of the gene that led to reductions in the function of PCSK-9 were associated with low LDL-cholesterol levels, and a lower incidence of vascular disease. That made the compelling case that PCSK-9 had a counter-regulatory function in LDL-cholesterol metabolism, so that interfering with its function would lead to lower cholesterol levels.
Continue reading The New Paradigm
I trained in internal medicine and cardiology at the tail end of the era of lifetime board certification by the American Board of Internal Medicine. In fact, my timing was perfect – I was “boarded” in medicine in 1987, and in cardiovascular disease in 1989, which (I am pretty sure) were, respectively, the last years that the ABIM offered certificates without an expiration date in those disciplines. Continue reading Maintenance of Certification or Extortion?
There was a really interesting article in the business section of the New York Times recently entitled “The mental strain of making do with less.” In it, Sundhil Mullainathan shares some insights from his new book, “Scarcity: why having too little means so much.”
The basic premise is that each of us has only so much “mental bandwidth,” and that coping with psychological stress – in particular the stress associated with poverty – leaves the poor with less mental energy or capacity to deal with everyday life. It is a fascinating and profound proposition. As Mullainathan points out, looking at the world this way could turn a lot of stereotypes on their heads: what if “poor people make bad choices in life” is really a reflection of “being poor makes you less able to make good choices”?
Continue reading Stress and Health