Discovering New Benefits From Old Drugs With Big Data—Promise for Parkinson Disease

Olsen, Abby L.; Riise, Trond; Scherzer, Clemens R.

doi:10.1001/jamaneurol.2018.0345

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…The study observed a 28% higher incidence rate of PD in IBD patients than in unaffected matched controls. In IBD patients, anti-TNF treatment resulted in 78% reduction in the rate of PD incidence relative to patients that did not receive the treatment [ 120 , 121 ]. A similar approach was reported by Slade et al They conducted experiments on rats to investigate the effects of Attention Deficit Hyperactivity Disorder (ADHD) medication (type and timing) on the “rats’ propensity to exhibit addiction-like behavior”, which led to the hypothesis that initiating ADHD medication in adolescence “may increase the risk for SUD in adulthood”.…”

Section: Existing Solutionsmentioning

confidence: 99%

The evolution of Big Data in neuroscience and neurology

et al. 2023

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Neurological diseases are on the rise worldwide, leading to increased healthcare costs and diminished quality of life in patients. In recent years, Big Data has started to transform the fields of Neuroscience and Neurology. Scientists and clinicians are collaborating in global alliances, combining diverse datasets on a massive scale, and solving complex computational problems that demand the utilization of increasingly powerful computational resources. This Big Data revolution is opening new avenues for developing innovative treatments for neurological diseases. Our paper surveys Big Data’s impact on neurological patient care, as exemplified through work done in a comprehensive selection of areas, including Connectomics, Alzheimer’s Disease, Stroke, Depression, Parkinson’s Disease, Pain, and Addiction (e.g., Opioid Use Disorder). We present an overview of research and the methodologies utilizing Big Data in each area, as well as their current limitations and technical challenges. Despite the potential benefits, the full potential of Big Data in these fields currently remains unrealized. We close with recommendations for future research aimed at optimizing the use of Big Data in Neuroscience and Neurology for improved patient outcomes.

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Section: Existing Solutionsmentioning

confidence: 99%

The evolution of Big Data in neuroscience and neurology

et al. 2023

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“…4 Repurposing existing drugs represents an attractive alternative to traditional drug development. 5…”

Section: Introductionmentioning

confidence: 99%

“…4 Repurposing existing drugs represents an attractive alternative to traditional drug development. 5 We have conducted hypothesis-free analyses using data from Norwegian health registries to evaluate associations between any of the drugs used in Norway over a period of 15 years and the risk of developing PD. In a previous study, we linked drug effects demonstrated through experiments in cells and animals to corresponding associations in humans using these registries.…”

Section: Introductionmentioning

confidence: 99%

Association Between Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease

Romanowska,

Bjornevik,

Cortese

et al. 2023

Neurology

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Background and objectives: The incidence rate of Parkinson’s disease (PD) has been increasing rapidly during the last years. Yet, no treatments exist to prevent or slow the progression of the disease. Moreover, we are unable to detect early disease stages during which intervention with disease-modifying therapies is most likely to succeed. The objective of this study was to perform an agnostic drug-wide association study (DWAS) estimating the association between use of any of the drugs prescribed in Norway and the subsequent risk of PD. Methods: This registry-based cohort study use data from the entire Norwegian population between 2004–2019 linked to the Norwegian Prescription Registry, with more than 600 million individual prescriptions. Drug classes were screened according to ATC codes at level 2, corresponding to therapeutic subgroups. We used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for the associations between drug classes and PD risk. All p-values were corrected for multiple testing using the false discovery rate. Additionally, we conducted sensitivity analyses of exposure definition, as well as time-lag and dose-response analyses. Results: The study population comprised 3,223,672 individuals, 15,849 of whom developed PD during the follow-up. We identified thirty-one drug classes that were statistically significantly associated with PD risk in Norway during the follow-up. Drugs acting on the renin-angiotensin system (HR = 0.92, 95% CI: 0.89–0.95), corticosteroids for systemic use (0.88, 95% CI: 0.84–0.93), and vaccines (0.89, 95% CI: 0.82–0.96) were associated with a decreased risk of PD even up to 10 years prior to PD onset. Drug classes used to treat symptoms related to prodromal signs of PD such as constipation, urological issues, and depression were associated with an increased risk of subsequent diagnosis of PD with HRs of 1.6 (95% CI: 1.49–1.73), 1.48 (1.42–1.53), and 1.94 (1.87–2.01), respectively. Discussion: This drug-wide study identified thirty-one drug classes that were associated with the PD risk change. It reveals links of renin-angiotensin system medications, vaccines, and corticosteroids with PD risk and suggests that monitoring drug usage using pharmacoepidemiology may allow identifying individuals with prodromal PD.

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“…Additionally, it has been demonstrated that the induction of PD-like symptoms in humanized CD34 + mice using MPTP can cause an associated neuroinflammatory response that was attenuated using FK506, an immunosuppressant drug. Based on these and other studies, it has been suggested that anti-inflammatory medications may have utility in PD [16][17][18][19][20]. In fact, one recent study demonstrated that probiotic intake impacted inflammatory gene expression in PD patients after 12-weeks [21] with another showing that probiotic supplementation reduced inflammation and decreased MDS-UPDRS scores [22].…”

Section: Introductionmentioning

confidence: 99%

Analysis of a precision medicine approach to treating Parkinson's disease: Analysis of the DATATOP study

O’Bryant

Petersen

Zhang

et al. 2022

Parkinsonism & Related Disorders

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The aim of this study was to examine the potential application of a targeted proteomic predictive biomarker comprised predominantly of inflammatory proteins in distinguishing those who responded to a previously conducted clinical trial for Parkinson's disease (PD). Methods: Plasma samples obtained from a biorepository were assayed from a total of n = 520 DATATOP (Deprenyl And Tocopherol Antioxidative Therapy Of Parkinsonism) clinical trial participants across treatment arms. Support vector machine analyses were conducted to distinguish responder status on primary (need for Levodopa) and secondary trial endpoints (UPDRS Motor and Total Scores).Results: For the α-tocopherol and deprenyl placebo treatment arm (TOC), the targeted proteomic biomarker was able to distinguish responder status with an accuracy (area under the curve [AUC]) of 91% for the primary endpoint while it was 100% across secondary endpoints. For the deprenyl and α-tocopherol placebo treatment arm (DEP), the AUC was 93% for the primary endpoint and 99-100% for the secondary endpoints. For the combined treatment arm, AUC was 87% for the primary and 94-96% for the secondary endpoints. Discussion: The targeted proteomic predictive biomarker was highly accurate in distinguishing responder status across treatment arms thereby supporting the application of a precision medicine approach to treating PD.

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Discovering New Benefits From Old Drugs With Big Data—Promise for Parkinson Disease

Abstract: 8.Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases.

Cited by 5 publications

References 16 publications

The evolution of Big Data in neuroscience and neurology

The evolution of Big Data in neuroscience and neurology

Association Between Use of Any of the Drugs Prescribed in Norway and the Subsequent Risk of Parkinson Disease

Analysis of a precision medicine approach to treating Parkinson's disease: Analysis of the DATATOP study

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