I have previously blogged about the experimental use of statins in animal models of prion disease. All four studies that have examined this issue found that statins prolonged survival time in prion-infected mice [Mok 2006, Kempster 2007, Haviv 2008 (ft), Vetrugno 2009 (ft)]. The effect is modest (~10% delay in onset or death) and the mechanism of action with regards to prion disease is best described as unknown, but the effect has been replicated across three different prion strains (139A, ME7 and RML), two different inbred mouse lines (C57BL/6 and FVB/N) and two different statin drugs (simvastatin and pravastatin), and the drugs appear to have some effect even when administered late in infection or in low doses. Those are all good signs that the effect is something real.
Today I found this interesting presentation by Dr. Brian Appleby from the Prion 2009 conference:
Slides 30-35 discuss some statistics on a handful of sCJD patients (n=21) for whom lipid profiles were available. One of the clinical blood lipid values considered is LDLs (low-density lipoprotein, often colloquially referred to as ‘bad cholesterol’). It looks suggestive, at least, that patients with elevated LDL levels (over 120 mg/dL) had shorter survival time than patients whose LDLs were more within the healthy range. There are several disclaimers to that, of course. These data don’t appear to have been published yet and haven’t been peer reviewed. It’s not yet clear how statistically significant the result is, and there may be confounding factors as well. And survival time after onset of symptoms (measured here) is not the same as time to onset of symptoms (which is what I’m more interested in). Still, these data are interesting and are suggestive, at least, that lipids may matter in human prion diseases.
Notice that slide 32 looks at four lipid variables: LDL, HDL, triglycerides and ‘cholesterol’. Cholesterol here presumably means total cholesterol = HDL+LDL+VLDL. Of these variables, only LDL was significant. If true, this might actually make perfect sense. It’s been reported that PrPSc from human sCJD patients binds to both LDL and VLDL but not to HDL [Safar 2006]. On the other hand, the mechanism by which this would influence prion disease progression is not obvious – as Safar notes, apolipoprotein B (apoB; gene: APOB), the protein component of LDL, is not expressed in the brain nor found in cerebrospinal fluid, even though neurons do express apoB receptors [Pitas 1987 (ft)].