期刊
MULTIPLE SCLEROSIS JOURNAL
卷 11, 期 2, 页码 159-165出版社
SAGE PUBLICATIONS LTD
DOI: 10.1191/1352458505ms1143oa
关键词
intercellular adhesion molecule-1; lipoic acid; matrix metalloproteinase-9; multiple sclerosis; pharmacokinetics
资金
- NCCIH NIH HHS [P50 AT00066-01] Funding Source: Medline
- NCRR NIH HHS [5 M01 RR00334] Funding Source: Medline
- NATIONAL CENTER FOR COMPLEMENTARY &ALTERNATIVE MEDICINE [P50AT000066] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000334] Funding Source: NIH RePORTER
Lipoic acid (LA) is an antioxidant that suppresses and treats an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis. The purpose of this study was to determine the pharmacokinetics (PK), tolerability and effects on matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAM-1) of oral LA in patients with MS. Thirty-seven MS subjects were randomly assigned to one of four groups: placebo, LA 600 mg twice a day, LA 1200 mg once a day and LA 1200 mg twice a day. Subjects took study capsules for 14 days. We found that subjects taking 1200 mg LA had substantially higher peak serum LA levels than those taking 600 mg and that peak levels varied considerably among subjects. We also found a significant negative correlation between peak serum LA levels and mean changes in serum MMP-9 levels (tau=-0.263, P=0.04). There was a significant dose response relationship between LA and mean change in serum sICAM-1 levels (P=0.03). We conclude that oral LA is generally well tolerated and appears capable of reducing serum MMP-9 and sICAM-1 levels. LA may prove useful in treating MS by inhibiting MMP-9 activity and interfering with T-cell migration into the CNS.
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