Pioglitazone use and Parkinson’s disease: a retrospective cohort study in Taiwan

Wu, Hsiu-Feng; Shih, Jui‐Hu; Kao, Hui-Han; Chou, Yu‐Ching; Li, I‐Hsun; Kao, Senyeong

doi:10.1136/bmjopen-2018-023302

Cited by 24 publications

(29 citation statements)

References 36 publications

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“…It also mitigates the reduction of DA in striatum of rotenone-treated rats [ 259 ]. However, a population-based study does not find the relationship between pioglitazone use and PD incidence among diabetic patients [ 260 ]. A randomized, double-blind, placebo-controlled trial of pioglitazone (15 or 45 mg/day) on 210 PD patients could not show a difference of UPDRS scores between treatment and placebo groups ( Table 2 ) [ 261 ].…”

Section: Potentials Of Antioxidants In Treating Parkinson’s Diseasmentioning

confidence: 99%

The Role of Oxidative Stress in Parkinson’s Disease

2020

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Parkinson’s disease (PD) is caused by progressive neurodegeneration of dopaminergic (DAergic) neurons with abnormal accumulation of α-synuclein in substantia nigra (SN). Studies have suggested the potential involvement of dopamine, iron, calcium, mitochondria and neuroinflammation in contributing to overwhelmed oxidative stress and neurodegeneration in PD. Function studies on PD-causative mutations of SNCA, PRKN, PINK1, DJ-1, LRRK2, FBXO7 and ATP13A2 further indicate the role of oxidative stress in the pathogenesis of PD. Therefore, it is reasonable that molecules involved in oxidative stress, such as DJ-1, coenzyme Q10, uric acid, 8-hydroxy-2’-deoxyguanosin, homocysteine, retinoic acid/carotenes, vitamin E, glutathione peroxidase, superoxide dismutase, xanthine oxidase and products of lipid peroxidation, could be candidate biomarkers for PD. Applications of antioxidants to modulate oxidative stress could be a strategy in treating PD. Although a number of antioxidants, such as creatine, vitamin E, coenzyme Q10, pioglitazone, melatonin and desferrioxamine, have been tested in clinical trials, none of them have demonstrated conclusive evidence to ameliorate the neurodegeneration in PD patients. Difficulties in clinical studies may be caused by the long-standing progression of neurodegeneration, lack of biomarkers for premotor stage of PD and inadequate drug delivery across blood–brain barrier. Solutions for these challenges will be warranted for future studies with novel antioxidative treatment in PD patients.

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Section: Potentials Of Antioxidants In Treating Parkinson’s Diseasmentioning

confidence: 99%

The Role of Oxidative Stress in Parkinson’s Disease

2020

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“…One study was excluded because of failure to be related to the incidence of PD. Ultimately, the remaining five qualified studies [9–13] involving 347,556 patients were considered suitable for this meta-analysis. The Kappa for agreement between the two independent investigators was 0.8.…”

Section: Resultsmentioning

confidence: 99%

“…Three [9,10,12] studies showed that TZDs use was associated with a reduced incidence of PD, whereas the other 2 [11,13] studies did not find such association. Pooled analysis of the 5 included studies showed that the OR was statistically significant (OR, 0.70; 95% CI, 0.51 to 0.96; p = 0.03; Fig 2A), in spite of obvious heterogeneity (Chi 2 , 28.25; I 2 = 86%; p < 0.0001; tau 2 = 0.10), indicating that the use of TZDs was associated with significantly reduced risk of PD in diabetic patients with TZDs treatment compared with those without.…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, one randomized controlled trial (RCT) indicated that pioglitazone is unlikely to be able to slow the disease progression in early PD patients without diabetes [8]. To date, several retrospective observational cohort studies have assessed the association between the TZDs use and the incidence of PD in diabetic patients, but with controversial results [9–13]. Although RCT studies are considered more reliable to confirm the treatment effectiveness, observational studies can overcome the limited generalizability and inadequate follow-up to identify rare adverse effects of RCTs, the outcomes of which can help guide the future RCT design.…”

Section: Introductionmentioning

confidence: 99%

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Decreased risk of Parkinson’s disease in diabetic patients with thiazolidinediones therapy: An exploratory meta-analysis

Zhu

Chen

et al. 2019

PLoS ONE

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BackgroundIt has been found that thiazolidinediones (TZDs) may play a protective role in animal models of Parkinson’s disease (PD), while the results remain controversial whether TZDs protect against Parkinson’s disease in humans. The purpose of this meta-analysis is to explore the association between TZDs use and the incidence of PD in diabetic patients.MethodsA systematic online search was conducted to find studies published up to 31 December 2018. In our exploratory meta-analysis, studies comparing incidence of PD between TZD-treated and non-TZD-treated groups of diabetic patients were included. Data analysis was performed using a random or fixed effects model and expressed as odds ratios (OR) with 95% confidence interval (95% CI). We used the Cochrane Collaboration’s Review Manager 5.3 software to analyze data.ResultsIn total, 5 retrospective observational cohort studies were identified which met the inclusion criteria. The pooled odds ratio (OR) was 0.70 [95% CI, 0.51 to 0.96; p = 0.03] in a random-effects model, indicating a 30% lower risk of developing PD in diabetic patients treated with TZDs compared with non-TZD-treated patients.ConclusionIn this exploratory meta-analysis, we found that TZDs use was associated with reduced risk of PD in diabetic patients. However, this meta-analysis was not registered online although we followed a protocol designed for it. Further prospective observational studies with larger sample size and more strict inclusion criteria including controlling for diabetes complication severity index, hypoglycemic drugs combination, sex ratio, and comorbidity are needed to guide whether RCTs are warranted. And RCTs can better determine whether TZDs use could lower incidence of PD in diabetic patients.

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“…Finally, the use of coenzyme Q10, a potent antioxidant, failed to demonstrate an improvement in clinical trials [40]. Neither pioglitazone [41,42] nor genomic strategies to increase neurturin (AAV-mediated gene therapy) succeeded in the clinical trials [43,44], since disease-modifying activity was not demonstrated.…”

Section: Therapeutic Strategies For Parkinson's Diseasementioning

confidence: 99%

Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

et al. 2020

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Neuroinflammation is a crucial process associated with the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Several pieces of evidence suggest an active role of lipid mediators, especially epoxy-fatty acids (EpFAs), in the genesis and control of neuroinflammation; 14,15-epoxyeicosatrienoic acid (14,15-EET) is one of the most commonly studied EpFAs, with anti-inflammatory properties. Soluble epoxide hydrolase (sEH) is implicated in the hydrolysis of 14,15-EET to its corresponding diol, which lacks anti-inflammatory properties. Preventing EET degradation thus increases its concentration in the brain through sEH inhibition, which represents a novel pharmacological approach to foster the reduction of neuroinflammation and by end neurodegeneration. Recently, it has been shown that sEH levels increase in brains of PD patients. Moreover, the pharmacological inhibition of the hydrolase domain of the enzyme or the use of sEH knockout mice reduced the deleterious effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. This paper overviews the knowledge of sEH and EETs in PD and the importance of blocking its hydrolytic activity, degrading EETs in PD physiopathology. We focus on imperative neuroinflammation participation in the neurodegenerative process in PD and the putative therapeutic role for sEH inhibitors. In this review, we also describe highlights in the general knowledge of the role of sEH in the central nervous system (CNS) and its participation in neurodegeneration. We conclude that sEH is one of the most promising therapeutic strategies for PD and other neurodegenerative diseases with chronic inflammation process, providing new insights into the crucial role of sEH in PD pathophysiology as well as a singular opportunity for drug development.

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Pioglitazone use and Parkinson’s disease: a retrospective cohort study in Taiwan

Cited by 24 publications

References 36 publications

The Role of Oxidative Stress in Parkinson’s Disease

The Role of Oxidative Stress in Parkinson’s Disease

Decreased risk of Parkinson’s disease in diabetic patients with thiazolidinediones therapy: An exploratory meta-analysis

Soluble Epoxide Hydrolase Inhibition to Face Neuroinflammation in Parkinson’s Disease: A New Therapeutic Strategy

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