Statins and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis

Nabizadeh, Fardin; Balabandian, Mohammad; Sharafi, Amir Mohammad; Ghaderi, Ali; Rostami, Mohammad Reza; Moghadasi, Abdorreza Naser

doi:10.1007/s13760-021-01753-8

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…A systematic meta-analysis found no association between statin use and ALS risk (Chang et al, 2021 ). A recent meta-analysis and systematic review of 13,890 ALS patients from eight clinical studies revealed no significant association between prolonged use of statins and ALS risk (Nabizadeh et al, 2022 ). Other systematic reviews and meta-analyses illustrated that prolonged use of statins was not linked with ALS risk (Hu and Ji, 2022 ).…”

Section: Role Of Statins In Alsmentioning

confidence: 99%

“…As ALS is more common in older age groups having comorbidities such as diabetes, hypertension, and dyslipidemia, the use of lipid-lowering agents such as statins is more frequent in those patients (Hu and Ji, 2022 ). It has been demonstrated that statins may have beneficial or detrimental effects on the pathogenesis of ALS (Nabizadeh et al, 2022 ; Wang et al, 2023 ). Thus, this review aims to discuss the potential effects of statins on ALS neuropathology.…”

Section: Introductionmentioning

confidence: 99%

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The role of statins in amyotrophic lateral sclerosis: protective or not?

Al-kuraishy,

Jabir,

Sulaiman

et al. 2024

Front. Neurosci.

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of motor neurons characterized by muscle weakness, muscle twitching, and muscle wasting. ALS is regarded as the third-most frequent neurodegenerative disease, subsequent to Alzheimer's disease (AD) and Parkinson's disease (PD). The World Health Organization (WHO) in 2007 declared that prolonged use of statins may induce development of ALS-like syndrome and may increase ALS risk. Subsequently, different studies have implicated statins in the pathogenesis of ALS. In contrast, results from preclinical and clinical studies highlighted the protective role of statins against ALS neuropathology. Recently, meta-analyses and systematic reviews illustrated no association between long-term use of statins and ALS risk. These findings highlighted controversial points regarding the effects of statins on ALS pathogenesis and risk. The neuroprotective effects of statins against the development and progression of ALS may be mediated by regulating dyslipidemia and inflammatory changes. However, the mechanism for induction of ALS neuropathology by statins may be related to the dysregulation of liver X receptor signaling (LXR) signaling in the motor neurons and reduction of cholesterol, which has a neuroprotective effect against ALS neuropathology. Nevertheless, the exact role of statins on the pathogenesis of ALS was not fully elucidated. Therefore, this narrative review aims to discuss the role of statins in ALS neuropathology.

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Section: Role Of Statins In Alsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The role of statins in amyotrophic lateral sclerosis: protective or not?

Al-kuraishy,

Jabir,

Sulaiman

et al. 2024

Front. Neurosci.

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“…Recent studies have shown dysmetabolism of various lipid classes, such as fatty acids, glycerolipids, glycerophospholipids, sphingolipids, and sterols, in ALS patients (Agrawal et al., 2022; Liu et al., 2020; Nabizadeh et al., 2022). Lipids are believed to play a significant role in ALS pathogenesis and hold promise as both biomarkers and therapeutic targets.…”

Section: Lipid Metabolism and Alsmentioning

confidence: 99%

Induced pluripotent stem cells‐based disease modeling, drug screening, clinical trials, and reverse translational research for amyotrophic lateral sclerosis

Okano,

Morimoto,

Kato

et al. 2023

Journal of Neurochemistry

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It has been more than 10 years since the hopes for disease modeling and drug discovery using induced pluripotent stem cell (iPSC) technology boomed. Recently, clinical trials have been conducted with drugs identified using this technology, and some promising results have been reported. For amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, several groups have identified candidate drugs, ezogabine (retigabine), bosutinib, and ropinirole, using iPSCs‐based drug discovery, and clinical trials using these drugs have been conducted, yielding interesting results. In our previous study, an iPSCs‐based drug repurposing approach was utilized to show the potential of ropinirole hydrochloride (ROPI) in reducing ALS‐specific pathological phenotypes. Recently, a phase 1/2a trial was conducted to investigate the effects of ropinirole on ALS further. This double‐blind, randomized, placebo‐controlled study confirmed the safety and tolerability of and provided evidence of its ability to delay disease progression and prolong the time to respiratory failure in ALS patients. Furthermore, in the reverse translational research, in vitro characterization of patient‐derived iPSCs‐motor neurons (MNs) mimicked the therapeutic effects of ROPI in vivo, suggesting the potential application of this technology to the precision medicine of ALS. Interestingly, RNA‐seq data showed that ROPI treatment suppressed the sterol regulatory element‐binding protein 2‐dependent cholesterol biosynthesis pathway. Therefore, this pathway may be involved in the therapeutic effect of ROPI on ALS. The possibility that this pathway may be involved in the therapeutic effect of ALS was demonstrated. Finally, new future strategies for ALS using iPSCs technology will be discussed in this paper.

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“…Recent advancements in neuroscience have clarified the etiology of intractable CNS disorders and identified target molecules, leading to the development of therapeutic agents for such disorders [ 1 , 2 , 3 , 4 , 5 , 6 ]. However, due to the peculiarities of the CNS, the delivery of therapeutic agents to target tissues and cells in the CNS is difficult, hampering their clinical application [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification

Fukui

Tateno

Nakamura

et al. 2022

IJMS

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Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats. Liposomes in cell bodies were detected with infrared fluorescence of DiD conjugated to liposomes. Three days later, all nerve-administered liposomes were retrogradely transported to the spinal cord and DRGs, whereas only muscle-administered liposomes consisting of DSPC reached the spinal cord and DRGs. Modification with Cholera toxin B subunit improved the transport efficiency of liposomes to the spinal cord and DRGs from 4.5% to 17.3% and from 3.9% to 14.3% via nerve administration, and from 2.6% to 4.8% and from 2.3% to 4.1% via muscle administration, respectively. Modification with octa-arginine (R8) improved the transport efficiency via nerve administration but abolished the transport capability via muscle administration. These findings provide the initial data for the development of a novel DDS targeting the spinal cord and DRGs via peripheral administration.

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Statins and risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis

Cited by 9 publications

References 49 publications

The role of statins in amyotrophic lateral sclerosis: protective or not?

The role of statins in amyotrophic lateral sclerosis: protective or not?

Induced pluripotent stem cells‐based disease modeling, drug screening, clinical trials, and reverse translational research for amyotrophic lateral sclerosis

Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification

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