Synonyms: Lopid, Jezil, Gen-Fibro
Therapy Type: Small Molecule (timeline)
Target Type: Cholesterol
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 0)
Approved for: Hyperlipidemia
Gemfibrozil is an old member of the fibrate class of drugs. Fibrates activate peroxisome proliferator-activated receptor-α (PPARα), nuclear receptors involved in lipid metabolism. Thereby fibrates reduce triglycerides levels; they are widely prescribed to control cholesterol and for related indications.
More recently, gemfibrozil in particular has been considered to increase expression of microRNA 107 (see NIH GrantOme). Expression of miR107 has been reported to be reduced in Alzheimer's disease and implicated in regulating BACE levels (see Feb 2008 news; Nelson and Wang, 2010; Hebert et al., 2013). MiR107 has also been reported to be expressed in cerebrovascular endothelial cells, and proposed as a biomarker for mild cognitive impairment or Alzheimer's disease (Wang et al., 2014; Wang et al., 2015; Liu et al., 2016; Wang et al., 2016). Panels for measuring CSF microRNA in neurodegeneration research are being developed (Wang et al., 2016).
For all trials of gemfibrozil, see clinicaltrials.gov.
In May 2014, an NIA-funded trial at the University of Kentucky started to evaluate whether gemfibrozil can safely modulate microRNA-107 levels for the prevention or early stage treatment of AD. The study enrolls 48 cognitively normal and 24 mildly impaired (CDR 0.5) participants for a one-year, twice-daily course of 600 mg gemfibrozil or placebo. As primary outcomes, the trial assesses adverse events, blood and CSF gemfibrozil levels, and CSF Aβ40 and 42 levels. Secondary outcomes include two cognitive tests known to be sensitive at early stages, the Free and Cued Selective Reminding Test (FCSRT) and the Paired Associates Learning (PAL) tests. The trial is set to run until summer 2016.
- Nelson PT, Wang WX. MiR-107 is reduced in Alzheimer's disease brain neocortex: validation study. J Alzheimers Dis. 2010;21(1):75-9. PubMed.
- Hébert SS, Wang WX, Zhu Q, Nelson PT. A Study of Small RNAs from Cerebral Neocortex of Pathology-Verified Alzheimer's Disease, Dementia with Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, and Non-Demented Human Controls. J Alzheimers Dis. 2013 Jan 1;35(2):335-48. PubMed.
- Wang WX, Danaher RJ, Miller CS, Berger JR, Nubia VG, Wilfred BS, Neltner JH, Norris CM, Nelson PT. Expression of miR-15/107 family microRNAs in human tissues and cultured rat brain cells. Genomics Proteomics Bioinformatics. 2014 Feb;12(1):19-30. Epub 2014 Jan 28 PubMed.
- Wang T, Chen K, Li H, Dong S, Su N, Liu Y, Cheng Y, Dai J, Yang C, Xiao S. The feasibility of utilizing plasma miRNA107 and BACE1 messenger RNA gene expression for clinical diagnosis of amnestic mild cognitive impairment. J Clin Psychiatry. 2015 Feb;76(2):135-41. PubMed.
- Liu W, Cai H, Lin M, Zhu L, Gao L, Zhong R, Bi S, Xue Y, Shang X. MicroRNA-107 prevents amyloid-beta induced blood-brain barrier disruption and endothelial cell dysfunction by targeting Endophilin-1. Exp Cell Res. 2016 May 1;343(2):248-57. Epub 2016 Mar 30 PubMed.
- Wang T, Shi F, Jin Y, Jiang W, Shen D, Xiao S. Abnormal Changes of Brain Cortical Anatomy and the Association with Plasma MicroRNA107 Level in Amnestic Mild Cognitive Impairment. Front Aging Neurosci. 2016;8:112. Epub 2016 May 18 PubMed.
- Wang WX, Fardo DW, Jicha GA, Nelson PT. A Customized Quantitative PCR MicroRNA Panel Provides a Technically Robust Context for Studying Neurodegenerative Disease Biomarkers and Indicates a High Correlation Between Cerebrospinal Fluid and Choroid Plexus MicroRNA Expression. Mol Neurobiol. 2016 Nov 29; PubMed.
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