Zocor (simvastatin) is a type of statin, or cholesterol-lowering medication, produced by Merck (known as MSD outside the U.S. and Canada). It is being investigated as a therapy to manage the symptoms of scleroderma.
How Zocor works
Zocor acts by inhibiting an enzyme called HMG-CoA reductase, which is involved in the production of cholesterol in the liver. High levels of cholesterol can cause heart and vascular disease. By blocking the activity of HMG-CoA reductase, Zocor can reduce cholesterol in the body to a safer level.
Zocor may also have other effects in the body, including altering the immune response and regulating the vascular system.
In scleroderma, the dysfunctional immune system damages healthy connective tissue in the body, triggering the overproduction of collagen. As a major component of scar tissue, too much collagen results in the fibrosis, or scarring, of the skin and internal organs. A common symptom of this is restricted blood flow, leading to Raynaud’s phenomenon, digital ulcers, and pulmonary hypertension.
One potential cause for this is endothelial dysfunction. The vascular endothelium is a layer of cells in the walls of the arteries that are involved in vasodilation (the widening of the arteries to increase blood flow), and vasoconstriction (the narrowing of the arteries to restrict blood flow). Endothelial dysfunction in scleroderma is associated with the arteries not relaxing and possibly increased collagen production.
By lowering cholesterol levels, Zocor may improve blood flow, since high cholesterol can block arteries. Zocor is also thought to act independently to improve endothelial function and reduce the damaging immune responses, such as inflammation and fibrosis. This may help widen arteries, allowing blood to flow more easily, and potentially reduce fibrosis in internal organs.
Zocor in clinical trials
Large-scale, randomized, controlled trials are still required to fully assess Zocor’s effect in scleroderma. However, early preclinical and clinical studies suggest it may have a benefit.
A study, published in the journal Rheumatology, assessed the effect of Zocor on fibrosis in mice with systemic scleroderma. The results suggested that Zocor could significantly reduce damage to the lungs from fibrosis and reduce skin thickness.
The effect of Zocor on the vascular system in systemic scleroderma has also been investigated in human trials. A study, published in the Journal of Rheumatology, recruited 40 people to investigate the effects of 20 mg of Zocor per day for 12 weeks. Half of the patients had systemic scleroderma with normal cholesterol levels, while the other half had high cholesterol levels but did not have scleroderma.
A peripheral blood sample was collected from the patients three times: once prior to treatment, once after 12 weeks of treatment, and once four weeks after stopping treatment. These samples were used to assess for markers of damage to the vascular system, endothelial activation (whether the arteries relax and constrict as normal), and immune proteins.
The results suggested that treatment with Zocor significantly improved endothelial activation. Moreover, the levels of inflammatory immune proteins were significantly reduced. Circulating endothelial cells, a marker of damage to the vascular system in systemic scleroderma, were also significantly reduced in the blood of scleroderma patients.
However, Zocor appeared ineffective in promoting healing in the vascular system in scleroderma as there was no significant increase in endothelial progenitor cells, which are involved in repairing and replacing damaged vascular cells.
Common side effects associated with Zocor include muscle cramps, muscle pain or tenderness, headaches, nausea, indigestion, flatulence, dizziness, fatigue, a tingling sensation, rashes, and thinning hair.
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