Drug Treatment to Reduce VLDL

SPX106T achieved statistically significant reductions in serum VLDL when used in apolipoprotein E-deficient (apoE -/-) mice prone to dyslipidemia. These new data provide additional mechanistic insight into earlier preclinical tests in apoE -/- mice that showed significant reductions in total serum cholesterol, fat deposition, and body weight in treatment with SPX106T (release of 10/24/11). Previously, studies by Spherix using a carbohydrate-supplemented diet in LDLr -/- mice have also shown that serum triglycerides are significantly reduced by SPX106T (release of 6/2/11).

Treatment of apoE -/- mice on a Western diet with low doses of SPX106T significantly reduced VLDL by 36% (from 315 to 201 mg/dl)(p=0.05). VLDL is the predominant lipoprotein particle in plasma of apoE -/-mice, and this lipoprotein particle accumulates in plasma because of the absence of apoE-mediated uptake of these particles in the knockout. VLDL is converted into LDL in the body. The reduction in LDL also observed with SPX106T in the mice is likely due at least in part to the reduction in VLDL. LDL can be atherogenic when elevated.

In some patients, omega-3-acid ethyl esters increase LDL levels. LDL levels should be monitored periodically during therapy with omega-3-acid ethyl esters. The fact that VLDL is significantly reduced by SPX106T suggests that SPX106T works in reducing triglycerides by a mechanism that is different than that of other drugs such as omega-3-acid ethyl esters. We recently had our pre-IND meeting with FDA and the effect of SPX106T on VLDL is described in the new IND about to be submitted.

Knockout studies can be important in elucidating the mechanisms of disease. The biochemistry of lipoproteins is complex, and as noted in DDDAS modeling, there are many possible points of intervention in treatment of dyslipidemia. The fact that SPX106T lowers triglycerides while it also lowers VLDL and LDL suggests that the therapy could offer important advantages over some other commonly used drugs for high cholesterol and triglycerides.