Promise of Pharmacogenomics for Drug Discovery, Treatment and Prevention of Parkinson's Disease. A Perspective

Payami, Haydeh; Factor, Stewart A.

doi:10.1007/s13311-013-0237-y

Cited by 15 publications

(13 citation statements)

References 58 publications

(67 reference statements)

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“…All potential medicines available to date are either under clinical trials or awaiting approval by the U.S. Food and Drug Administration (FDA). Around 40 medicines have been developed for the treatment of PD and related conditions [38]. Levodopa, dopamine agonists, COMT inhibitors, and anti-cholinergics are the classes/types of drugs most effectively used for the treatment of PD.…”

Section: Clinical Symptoms and Treatmentmentioning

confidence: 99%

Commonalities in Biological Pathways, Genetics, and Cellular Mechanism between Alzheimer Disease and Other Neurodegenerative Diseases: An In Silico-Updated Overview

Ahmad

Baig

Mushtaq

et al. 2017

CAR

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Background Alzheimer's disease (AD) is the most common and well-studied neurodegenerative disease (ND). Biological pathways, pathophysiology and genetics of AD show commonalities with other NDs viz. Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), Prion disease and Dentatorubral-pallidoluysian atrophy (DRPLA). Many of the NDs, sharing the common features and molecular mechanisms suggest that pathology may be directly comparable and be implicated in disease prevention and development of highly effective therapies. Method In this review, a brief description of pathophysiology, clinical symptoms and available treatment of various NDs have been explored with special emphasis on AD. Commonalities in these fatal NDs provide support for therapeutic advancements and enhance the understanding of disease manifestation. Conclusion The studies concentrating on the commonalities in biological pathways, cellular mechanisms and genetics may provide the scope to researchers to identify few novel common target(s) for disease prevention and development of effective common drugs for multi-neurodegenerative diseases.

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Section: Clinical Symptoms and Treatmentmentioning

confidence: 99%

Commonalities in Biological Pathways, Genetics, and Cellular Mechanism between Alzheimer Disease and Other Neurodegenerative Diseases: An In Silico-Updated Overview

Ahmad

Baig

Mushtaq

et al. 2017

CAR

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“…None of the current drugs can slow or stop neurodegeneration or halt clinical progression of symptoms. As the disease progresses, drug efficacy decreases, requiring higher and more frequent doses, which increase the risk of developing more serious side effects (see references for a review). There is wide interindividual variation in both the efficacy and toxicity of dopaminergic drugs .…”

Section: The Challengementioning

confidence: 99%

The emerging science of precision medicine and pharmacogenomics for Parkinson's disease

Payami

2017

Movement Disorders

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Current therapies for Parkinson’s disease are problematic because they are symptomatic and have adverse effects. New drugs have failed in clinical trials due to inadequate efficacy. At the core of the problem is trying to make one drug work for all Parkinson’s disease patients, when we know this premise is wrong because (a) Parkinson’s disease is not a single disease, and (b) no two individuals have the same biological make up. Precision medicine is the goal to strive for, but we are only at the beginning stages of building the infrastructure for one of the most complex projects in the history of science, and it will be a long time before Parkinson’s disease reaps the benefits. Pharmacogenomics, a cornerstone of precision medicine, has already proven successful for many conditions, and could also propel drug discovery and improve treatment for Parkinson’s disease. To make progress in pharmacogenomics of Parkinson’s disease, we need to change course from small inconclusive candidate gene studies to large-scale rigorously planned genome-wide studies that capture the nuclear genome and the microbiome. Pharmacogenomics studies must use homogenous subtypes of Parkinson’s disease, or apply brute force of statistical power to overcome heterogeneity which will require large sample sizes achievable only via internet-based methods and electronic databases. Large-scale pharmacogenomics studies, together with biomarker discovery efforts, will yield the knowledge necessary to design clinical trials with precision, to alleviate confounding by disease heterogeneity and inter-individual variability in drug response, two of the major impediments to successful drug discovery and effective treatment.

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“…Pharmacogenomics has the potential to change the way new drugs are developed, and the manner drugs are prescribed [6] via the use of genetic markers the drug response, its efficacy and potency can be predicted. Clinical trials will be designed to be enriched with individuals that are most in all likelihood to be benefitted by the drug, maximizing drug's efficacy, minimizing its unfavorable outcomes, and boosting the odds of successful discovery of drugs.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical trials will be designed to be enriched with individuals that are most in all likelihood to be benefitted by the drug, maximizing drug's efficacy, minimizing its unfavorable outcomes, and boosting the odds of successful discovery of drugs. Pharmacogenomics applied clinically will help physicians to accurately determine the right drugs, the right doses for right individuals [6]. It enables to avoid tedious trial and blunders approaches and keep away from detrimental impact consequently enhancing the patient compliance and improving the effectiveness of the therapy as well.…”

Section: Introductionmentioning

confidence: 99%

Critical Review of Pharmacogenomics in Antiparkinsonian Drug Therapy: Impact on Clinical Management of Parkinson’s Disease

Poornima

Bashir

2016

Asian J Pharm Clin Res

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Objective: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder characterized by rest tremors, bradykinesia, rigidity, postural instability, gait dysfunction, and several non-motor symptoms. The marked difference in drug response and adverse effect profile among patients led to search of genetic markers and polymorphism associated with response to antiparkinsonian drugs which will enable us to predict an individual's response to drugs in terms of both efficacy and toxicity. Hence, efforts to define the role of genetic polymorphism in optimizing pharmacotherapy of PD have been undertaken and some promising genetic loci for the treatment have been determined. Therefore, we aim to present a critical review of pharmacogenetic aspects of levodopa, dopamine agonists (DAs), and catecol-O-methyltransferase (COMT) inhibitors and describe gene polymorphism of interest for future research. Methods:The PubMed database was searched using the keywords "parkinsonism," "antiparkinsonian drugs," "levodopa," "DAs," "COMT inhibitors," "pharmacogenomics," and "polymorphism." Abstracts and review articles were included for the study. Results and Conclusion:Studies conducted in different settings suggest that pharmacogenomics plays a significant role in Parkinsonism drug therapy. The gene/drug pairings with the strongest potential for pharmacogenetic recommendations include COMT allele/levodopa and entacapone, dopamine D2 receptor (DRD2)/ropinirole, pramipexole, and DRD3/ropinirole and pramipexole. It can be concluded that with the rapid development of genotyping platforms, genome-wide association study can be performed to analyze polymorphism associated with inefficient treatment or adverse effects. Hence, individualized therapy of PD for better patient care can be achieved by targeted genetic testing.

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Promise of Pharmacogenomics for Drug Discovery, Treatment and Prevention of Parkinson's Disease. A Perspective

Cited by 15 publications

References 58 publications

Commonalities in Biological Pathways, Genetics, and Cellular Mechanism between Alzheimer Disease and Other Neurodegenerative Diseases: An In Silico-Updated Overview

Commonalities in Biological Pathways, Genetics, and Cellular Mechanism between Alzheimer Disease and Other Neurodegenerative Diseases: An In Silico-Updated Overview

The emerging science of precision medicine and pharmacogenomics for Parkinson's disease

Critical Review of Pharmacogenomics in Antiparkinsonian Drug Therapy: Impact on Clinical Management of Parkinson’s Disease

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