A Double‐Blind, Randomized, Controlled Trial of Lovastatin in Early‐Stage Parkinson's Disease

Abstract

Background Recent evidence indicates that lipophilic statins have a neuroprotective benefit in animal models of Parkinson's disease (PD). The objective of this study was to evaluate whether lovastatin has the potential to slow motor symptom progression in patients with early‐stage PD. Methods This double‐blind, randomized, placebo‐controlled trial enrolled 77 patients with early‐stage PD between May 23, 2017, and July 12, 2018, with follow‐up ending September 1, 2019. Lovastatin 80 mg/day or placebo with 1:1 randomization was administered for 48 weeks. Mean change in the parts I–III scores of the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), changes in the striatal dopamine uptake ratio measured by 18F‐dopa PET scan, and changes in PD medications between baseline and the week 48 visit were measured. Results Of the 77 randomized patients, 70 (90.9%) completed the study. There was a slightly beneficial trend of the MDS‐UPDRS motor score in the lovastatin group (−3.18 ± 5.50) compared with the placebo group (−0.50 ± 6.11); P = 0.14 adjusted for age, sex, disease duration, and baseline LEDD. Mean percentage change in the striatal 18F‐dopa uptake ratio deteriorated less in the lovastatin group than in the placebo group on the dominant side of caudate (1.2% ± 7.3% vs −7.1% ± 8.2%, P < 0.01) and putamen (2.3% ± 7.1% vs −6.4% ± 8.1%, P < 0.01). We found no between‐group differences in the change in part I or part II MDS‐UPDRS scores. Lovastatin was generally well tolerated. Conclusions Lovastatin treatment in patients with early‐stage PD was associated with a trend of less motor symptom worsening and was well tolerated. A future larger long‐term follow‐up study is needed to confirm our findings. © 2021 International Parkinson and Movement Disorder Society

Lovastatin Alleviates α-Synuclein Aggregation and Phosphorylation in Cellular Models of Synucleinopathy

“…Besides, lovastatin also attenuated oxidative stress and epigenetic dysregulation induced by α-syn PFFs. Our findings provide evidence supporting the protective effects of lovastatin in the development of PD pathology ( Lin et al, 2021 ), and shed light on applying the conventional cholesterol-lowering drug to PD management.…”

“…Recently, a double-blind, randomized, placebo-controlled trial including 77 patients with early-stage PD showed that administration of high-dose lovastatin in early-stage PD patients has a trend toward decreasing motor symptom progression and slowing the dopaminergic neuronal decline ( Lin et al, 2021 ). Besides, it has been reported that a large proportion of individuals with recent-onset PD have increased cardiovascular risk, which is associated with greater motor and cognitive severity, and greater axial impairment.…”

“…Several clinical studies have shown that statins, the commonly-used lipid-lowering drugs could reduce the risk of PD ( Lin et al, 2016 ; Swallow et al, 2016 ; Brakedal et al, 2017 ; Kawada, 2017 ; Carroll et al, 2019 ). A double−blind randomized placebo−controlled clinical trial found that lovastatin treatment was associated with a slower exacerbation of motor symptoms in PD patients ( Lin et al, 2021 ). In addition, statin administration prevents the onset of PD in patients with diabetes ( Lin et al, 2016 ).…”

Altered Cholesterol Homeostasis in Huntington’s Disease

“…In AD, several studies showed that statins can reduce the risk of the disease ( Wolozin et al, 2000 ; Rea et al, 2005 ; Sparks et al, 2005 ; Feldman et al, 2010 ; Lin et al, 2015 ) whereas no therapeutic effect was described in other studies ( Rea et al, 2005 ; Feldman et al, 2010 ). The clinical studies in PD have shown that the use of statins can reduce the risk of the disease ( Bai et al, 2016 ; Sheng et al, 2016 ), whereas other studies describe no effect of these molecules ( Huang X. et al, 2015 ; Liu et al, 2017 ; Rozani et al, 2017 ; Lin et al, 2021 ). If statins are primary used to lower cholesterol content, these molecules also show anti-inflammatory, anti-oxidative, and anti-excitotoxic properties that need to be considered in therapeutic options for neurodegenerative diseases, especially in HD.…”

Protein Kinase CK2 and Its Potential Role as a Therapeutic Target in Huntington’s Disease

“…Several kinases have been proposed to mediate pS129-αSyn in PD, including CK2 [ 125 , 142 , 187 , 196 ]. Commonly used lipid-lowering drugs such as Lovastatin, have shown an impact in decreasing motor symptom progression in patients with PD and they are beneficial for reducing the risk of PD [ 197 , 198 , 199 ]. A recent study showed that the underlying mechanism by which lovastatin mediates protective effects in PD is by inhibiting CK2 activity and decreasing pS129-αSyn [ 200 ].…”