Research published in the January 10, 2007, issue of the New England Journal of Medicine gives us a promising glimpse of the possibility of a new drug category on the horizon.
In this study, researchers examined patients with homozygous familial hypercholesterolemia, an inherited condition of high cholesterol in which LDL cholesterol (the “bad” cholesterol) is dangerously high and mostly unresponsive to current treatments out on the market.
Having this condition places these patients at a very high risk for cardiovascular disease and early death. Most of these individuals have had to resort to lowering their cholesterol levels though cholesterol apheresis , a process similar to dialysis, during which LDL cholesterol is filtered from the blood, with the blood being replaced into the patient’s body. Unfortunately, this process is fairly expensive, not readily available in some areas, and must be frequently repeated (up to twice a week). But the good news is that researchers at the University of Pennsylvania School of Medicine may have found a new option.
What Were The Results Of The Study?
This study examined six patients with defective LDL receptors and dangerously high LDL cholesterol levels who were not responsive to to current treatments. They were gives a drug labeled BMS-201038. This chemical blocks LDLS.One month before the study, the participants in the study were placed on a low-fat diet and their cholesterol lowering treatments were discontinued. BMS-201038 was introduced to the participants at this time, with incremental increases of the medication occurring every month. At the highest dose, it was found that BMS-201038 reduced LDL cholesterol by 58 percent and triglycerides by 65 percent in comparison to the participants’ LDL cholesterol and levels before taking the drug. Additionally, when BMS-201038 was taken at the highest dose, apolipoprotein B levels were reduced by 55 percent. HDL cholesterol levels did not appear to be affected by BMS-201038.
The most notable adverse effect seen in individuals taking BMS-201038 was elevated liver enzymes (aminotransferase ) and an increased accumulation of fat in the liver. This side effect was observed in two-thirds (four out of six) individuals in the study and appeared to return back to normal levels in most of the subjects within a month after the drug was discontinued.
What Do These New Findings Mean?
These new findings suggest that there might be an alternative for lowering cholesterol in those individuals where no other drug or procedure works. However, this potential class of drugs will not be in your pharmacy any time soon. There are still many long-term studies that need to be performed on BMS-201038, as well as other potential microsomal triglyceride transfer protein inhibitors, in order to determine the efficacy and safety of these drugs.One notable area of concern would be the accumulation of fat in the liver and elevated liver enzymes, which, in most cases, returned to normal levels with the exception of one patient, where the fatty liver condition persisted after the drug had been discontinued.
In any case, this study gives us a further understanding of how cholesterol and its associated molecules function in the body, which may open the door to future treatments.
Sources:
Cuchel M, Bloedon LT, Szapary PO, et al. Inhibition of Microsomal Triglyceride Transfer Protein in Familial Hypercholesterolemia. NEJM 2007; 356:148-156.
