Understanding the Potential of Genome Editing in Parkinson’s Disease

CRISPR is a simple and cost-efficient gene-editing technique that has become increasingly popular over the last decades. Various CRISPR/Cas-based applications have been developed to introduce changes in the genome and alter gene expression in diverse systems and tissues. These novel gene-editing techniques are particularly promising for investigating and treating neurodegenerative diseases, including Parkinson’s disease, for which we currently lack efficient disease-modifying treatment options. Gene therapy could thus provide treatment alternatives, revolutionizing our ability to treat this disease. Here, we review our current knowledge on the genetic basis of Parkinson’s disease to highlight the main biological pathways that become disrupted in Parkinson’s disease and their potential as gene therapy targets. Next, we perform a comprehensive review of novel delivery vehicles available for gene-editing applications, critical for their successful application in both innovative research and potential therapies. Finally, we review the latest developments in CRISPR-based applications and gene therapies to understand and treat Parkinson’s disease. We carefully examine their advantages and shortcomings for diverse gene-editing applications in the brain, highlighting promising avenues for future research.

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Adult Hippocampal Neurogenesis in Parkinson’s Disease: Impact on Neuronal Survival and Plasticity

Neural Plasticity ◽

10.1155/2014/454696 ◽

2014 ◽

Vol 2014 ◽

pp. 1-12 ◽

Cited By ~ 34

Author(s):

Martin Regensburger ◽

Iryna Prots ◽

Beate Winner

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Current Knowledge ◽

Treatment Options ◽

Hippocampal Neurogenesis ◽

Adult Brain ◽

Adult Hippocampal Neurogenesis ◽

Future Research ◽

Disease Mechanisms ◽

Newborn Neurons

In Parkinson’s disease (PD) and other synucleinopathies, chronic neurodegeneration occurs within different areas of the central nervous system leading to progressive motor and nonmotor symptoms. The symptomatic treatment options that are currently available do not slow or halt disease progression. This highlights the need of a better understanding of disease mechanisms and disease models. The generation of newborn neurons in the adult hippocampus and in the subventricular zone/olfactory bulb system is affected by many different regulators and possibly involved in memory processing, depression, and olfaction, symptoms which commonly occur in PD. The pathology of the adult neurogenic niches in human PD patients is still mostly elusive, but different preclinical models have shown profound alterations of adult neurogenesis. Alterations in stem cell proliferation, differentiation, and survival as well as neurite outgrowth and spine formation have been related to different aspects in PD pathogenesis. Therefore, neurogenesis in the adult brain provides an ideal model to study disease mechanisms and compounds. In addition, adult newborn neurons have been proposed as a source of endogenous repair. Herein, we review current knowledge about the adult neurogenic niches in PD and highlight areas of future research.

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Diagnosis, treatment and management of apathy in Parkinson’s disease: a scoping review

BMJ Open ◽

10.1136/bmjopen-2020-037632 ◽

2020 ◽

Vol 10 (9) ◽

pp. e037632

Author(s):

Bria Mele ◽

Shinia Van ◽

Jayna Holroyd-Leduc ◽

Zahinoor Ismail ◽

Tamara Pringsheim ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Scoping Review ◽

Current Knowledge ◽

Treatment Options ◽

Grey Literature ◽

Large Body ◽

Screening Tools ◽

Future Research ◽

Cochrane Central Register

ObjectiveTo conduct a scoping review of the literature on apathy in Parkinson’s disease (PD), to better understand how apathy in Parkinson’s disease is diagnosed, treated and managed.MethodsMEDLINE, Embase, PsycINFO, CINAHL, Cochrane Central Register of Control Trials and Cochrane Database of Systematic Reviews were searched to 17 May 2017. An updated review was run from 17 May 2017 to 28 January 2019. The grey literature was searched using the CADTH Grey Matters tool. Original peer-reviewed research was included if it included individuals with PD and apathy. Non-original data was only included if it was in the form of meta-analysis. All information regarding diagnosis, treatment and management of PD was extracted. Citation screening and extraction were performed in duplicate.ResultsFrom 11 375 citations, 362 articles were included in the final review. The majority of included studies focussed on prevalence, with few studies examining treatment. Twenty screening tools for apathy were identified. Fifty per cent of treatment studies were randomised control trials (RCTs). RCTs applied treatment methods including: exercise, mindfulness, rotigotine (Neupro) transdermal patch and rivastigmine (Exelon).ConclusionsThis review identified a large body of literature describing current knowledge on diagnosing, treating and managing apathy in PD. Future research should aim to detect an ideal screening tool for apathy in PD, to identify the best treatment options for apathy and the variety of comorbidities it may present with and finally aim to better understand postoperative apathy in those with deep brain stimulation.

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Gene therapy for Parkinson's disease: current knowledge and future perspective

Gene Therapy ◽

10.1038/sj.gt.3300449 ◽

1997 ◽

Vol 4 (6) ◽

pp. 504-506 ◽

Cited By ~ 2

Author(s):

MM Mouradian ◽

TN Chase

Keyword(s):

Parkinson’S Disease ◽

Gene Therapy ◽

Parkinson's Disease ◽

Current Knowledge ◽

Future Perspective

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Disorders of the Oral Cavity in Parkinson’s Disease and Parkinsonian Syndromes

Parkinson s Disease ◽

10.1155/2015/379482 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 18

Author(s):

Yair Zlotnik ◽

Yacov Balash ◽

Amos D. Korczyn ◽

Nir Giladi ◽

Tanya Gurevich

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Oral Cavity ◽

Orofacial Pain ◽

Current Knowledge ◽

Treatment Options ◽

The Body ◽

Controlled Trials ◽

Nonmotor Symptoms ◽

Parkinsonian Syndromes

Awareness of nonmotor symptoms of Parkinson’s disease is growing during the last decade. Among these, oral cavity disorders are, although prevalent, often neglected by the patients, their caregivers, and physicians. Some of these disorders include increased prevalence of caries and periodontal disease, sialorrhea and drooling, xerostomia, orofacial pain, bruxism, and taste impairment. Though many of these disorders are not fully understood yet and relatively few controlled trials have been published regarding their treatment, physicians should be aware of the body of evidence that does exist on these topics. This paper reviews current knowledge regarding the epidemiology, pathophysiology, and treatment options of disorders of the oral cavity in Parkinson’s disease patients.

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Evolving AAV-delivered therapeutics towards ultimate cures

Journal of Molecular Medicine ◽

10.1007/s00109-020-02034-2 ◽

2021 ◽

Author(s):

Xiangjun He ◽

Brian Anugerah Urip ◽

Zhenjie Zhang ◽

Chun Christopher Ngan ◽

Bo Feng

Keyword(s):

Gene Therapy ◽

Gene Editing ◽

Treatment Options ◽

Genetic Diseases ◽

The United States ◽

European Medicines Agency ◽

Gene Therapies ◽

Therapeutic Modalities ◽

United States Food

AbstractGene therapy has entered a new era after decades-long efforts, where the recombinant adeno-associated virus (AAV) has stood out as the most potent vector for in vivo gene transfer and demonstrated excellent efficacy and safety profiles in numerous preclinical and clinical studies. Since the first AAV-derived therapeutics Glybera was approved by the European Medicines Agency (EMA) in 2012, there is an increasing number of AAV-based gene augmentation therapies that have been developed and tested for treating incurable genetic diseases. In the subsequent years, the United States Food and Drug Administration (FDA) approved two additional AAV gene therapy products, Luxturna and Zolgensma, to be launched into the market. Recent breakthroughs in genome editing tools and the combined use with AAV vectors have introduced new therapeutic modalities using somatic gene editing strategies. The promising outcomes from preclinical studies have prompted the continuous evolution of AAV-delivered therapeutics and broadened the scope of treatment options for untreatable diseases. Here, we describe the clinical updates of AAV gene therapies and the latest development using AAV to deliver the CRISPR components as gene editing therapeutics. We also discuss the major challenges and safety concerns associated with AAV delivery and CRISPR therapeutics, and highlight the recent achievement and toxicity issues reported from clinical applications.

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The Past, Present, and Future of Parkinson's Disease Treatment

Open Science Journal ◽

10.23954/osj.v5i4.2622 ◽

2020 ◽

Vol 5 (4) ◽

Author(s):

Soyeon Park

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Viral Vectors ◽

Motor Fluctuation ◽

Alpha Synuclein ◽

Future Research ◽

Late 20Th Century ◽

Internal Globus Pallidus ◽

Gene Therapies ◽

Neuroprotective Therapies

Parkinson’s Disease was first introduced by James Parkinson in 1817. Since then, major strides have been made in the development of its treatment. Early treatments were dominated by traditional and complementary therapies, which were largely serendipitous and observation-based. Especially, the use of anticholinergics by Jean-Martin Charcot and his student Ordenstein prevailed in the late 20th century. Current drug-based therapies manifest in the form of levodopa accompanied by dopamine agonist, COMT inhibitor, or MAO-B inhibitor, for the purpose of reducing the levodopa-induced symptom fluctuation. In terms of surgical treatment, while ablative surgeries in the brain have been abandoned due to high mortality rate in the late 1900s, Deep Brain Stimulation in the subthalamic nucleus or internal globus pallidus has mostly replaced ablative surgeries since its introduction in 1987. Current research topics include non-dopaminergic agents for motor fluctuation reduction, transplantation of dopaminergic neurons, gene therapies using viral vectors, reduction of alpha-synuclein neurotoxicity, and neuroprotective therapies. Especially, due to the fact that the etiology of the disease is yet to be elucidated, neuroprotective therapies aimed at slowing or stopping disease progression are of particular interest. It is suggested that future research should aim towards clarifying the cause of the disease, for the development of a treatment that can permanently halt or reverse Parkinson’s Disease-related neurodegeneration.

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Current treatment options for Parkinson’s disease and the existing status of nanotechnology

International Journal of Research in Pharmaceutical Sciences ◽

10.26452/ijrps.v11i2.2232 ◽

2020 ◽

Vol 11 (2) ◽

pp. 2410-2423

Author(s):

Kannekanti Teja ◽

Asha Spandana K M ◽

Amit B Patil1 ◽

Vishakante Gowda D ◽

Narahari Rishitha

Keyword(s):

Parkinson’S Disease ◽

Drug Delivery ◽

Gene Therapy ◽

Central Nervous System ◽

Parkinson's Disease ◽

Nervous System ◽

Neurodegenerative Disorder ◽

Treatment Options ◽

Nano Particles ◽

The Central Nervous System

Parkinson's disease (PD) is a neurodegenerative disorder associated with dopaminergic neuron degeneration and/or loss of neuronal activity. Current idiopathic PD treatments focus primarily on the use of pharmacological agents to improve PD patients ' motor symptoms. PD remains to be an incurable disease so far. Therefore, the development of new therapeutic approaches for PD therapy is of utmost significance. Several molecular and gene therapy methods have been established over the past 20 years to counteract or retard the development of PD. Severe side effects are found in many native therapies. Therefore, novel therapeutic strategies remain in demand for development. Nanomedicine seems to be a significant medical application in nanotechnology that demonstrates promising future in drug delivery to the central nervous system. BBB stands throughout the central nervous system as a gateway to drug targeting. Drug delivery, based on nano-particles that always avoids Blood-Brain Barrier protection, Different potential therapies based on nanoparticles and nanosystems are explored various benefits. The scope of this review is to provide an overview of this field of PD-related therapies and significant breakthroughs. To do so, this review will begin by concentrating on PD characterization, pathophysiology, etiology and present therapy choices that subsequently cover molecular, gene therapy, and nanotechnology formulations that are currently being studied in animal PD models or lately tested in clinical trials.

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