scholarly journals Genotype-driven therapeutic developments in Parkinson’s disease

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jannik Prasuhn ◽  
Norbert Brüggemann
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Molecular Mechanisms ◽  
New Drugs ◽  
Main Body ◽  
Disease Development ◽  
Increased Risk ◽  
The Future ◽  
Challenges And Opportunities

Abstract Background Remarkable advances have been reached in the understanding of the genetic basis of Parkinson’s disease (PD), with the identification of monogenic causes (mPD) and a plethora of gene loci leading to an increased risk for idiopathic PD. The expanding knowledge and subsequent identification of genetic contributions fosters the understanding of molecular mechanisms leading to disease development and progression. Distinct pathways involved in mitochondrial dysfunction, oxidative stress, and lysosomal function have been identified and open a unique window of opportunity for individualized treatment approaches. These genetic findings have led to an imminent progress towards pathophysiology-targeted clinical trials and potentially disease-modifying treatments in the future. Main body of the manuscript In this review article we will summarize known genetic contributors to the pathophysiology of Parkinson’s disease, the molecular mechanisms leading to disease development, and discuss challenges and opportunities in clinical trial designs. Conclusions The future success of clinical trials in PD is mainly dependent on reliable biomarker development and extensive genetic testing to identify genetic cases. Whether genotype-dependent stratification of study participants will extend the potential application of new drugs will be one major challenge in conceptualizing clinical trials. However, the latest developments in genotype-driven treatments will pave the road to individualized pathophysiology-based therapies in the future.

New drugs in the future treatment of Parkinson's disease

2002 ◽  
Vol 249 (0) ◽  
pp. 1-1 ◽  
Author(s):  
Ruth Djaldetti ◽  
Eldad Melamed
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
New Drugs ◽  
Future Treatment ◽  
The Future

scholarly journals The Phenomenon of Brain World : Neuroculture in the Making by Patients with Parkinson’s Disease

2018 ◽  
Vol 10 (1) ◽  
pp. 102-114
Author(s):  
Markus Idvall
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Biomedical Research ◽  
Daily Life ◽  
Chronically Ill ◽  
Main Body ◽  
Embodied Experience ◽  
Clinical Neuroscience ◽  
The Brain

The aim of this article is to explore how the phenomenon of brain world, as a symptom of a possible emerging neuroculture, is perceived and enacted by patients with Parkinson’s disease, who, in their daily life, are subjected to neuroscience, most often as chronically ill individuals hoping for a cure, but also in some instances as participants in clinical trials. The article is based on a multifaceted ethnographic material that maps the experiences of biomedical research among patients with Parkinson’s. The main body of material consists of interviews carried out in 2012 and 2015, and comprises 19 transcripts of recorded conversations, conducted in groups as well as individually. The article argues that the exposure of the patients to clinical neuroscience gives birth to neuroculture. A materialist-discursive phenomenon called brain world—perceptions and enactments of the brain—is problematized on the basis of how patients cope with and reflect on their chronic illness in everyday life situations and in confrontation with clinical neuroscience. The embodied experience of the illness operates as the route into the brain world and also becomes the ground for how this world is featured with specific properties. Brain world is in this respect a contradictory entity: both plastic and fragile, both accessible and too complex, both strange and known. Most of all, brain world, in the eyes of the patients, relates to a territory still dominated by neuroscientists.

scholarly journals Association of Tooth Loss with New-Onset Parkinson’s Disease: A Nationwide Population-Based Cohort Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ho Geol Woo ◽  
Yoonkyung Chang ◽  
Ji Sung Lee ◽  
Tae-Jin Song
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Tooth Loss ◽  
Multivariable Analysis ◽  
Dopamine Neurons ◽  
Risk Indicator ◽  
Disease Development ◽  
National Health Insurance System ◽  
Increased Risk ◽  
New Onset

Introduction. Tooth loss is associated with poor oral hygiene. During insufficient oral sanitation, focal infection and inflammation can occur and these reactions may induce systemic inflammation. Systemic inflammatory reaction may be related to the degeneration of dopamine neurons in the substantia nigra. We hypothesized that tooth loss is related to increased risk of new-onset Parkinson’s disease. Methods. Between 2003 and 2006, we included 153,165 participants from the national health insurance system-health screening cohort in Korea. The incidence of new-onset Parkinson’s disease was defined as International Classification of Diseases-10 code “G20,” accompanying the prescription records for any anti-Parkinson’s disease medication. Results. Approximately 19.9% of the included participants had periodontal disease. After a median duration of 10.4 years, 1,227 (0.8%) cases of new-onset Parkinson’s disease were noted. The number of tooth loss was positively related to an increased risk of new-onset Parkinson’s disease. Contrastingly, the frequency of tooth brushings and dental clinic visits for any causes as well as competent dental care were negatively related to the development of new-onset Parkinson’s disease. In multivariable analysis, the number of tooth loss (≥15) was positively related to new-onset Parkinson’s disease development (hazard ratio: 1.38, 95% confidence interval (1.03–1.85), p=0.029, p for trend = 0.043) after adjusting variables. Conclusion. Our study demonstrated that the number of tooth loss was positively correlated with a higher risk of new-onset Parkinson’s disease development in a longitudinal study setting. Increased number of tooth loss may be an important risk indicator of new-onset Parkinson’s disease.

scholarly journals Parkinson’s Disease-Induced Zebrafish Models: Focussing on Oxidative Stress Implications and Sleep Processes

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Madalina-Andreea Robea ◽  
Ioana-Miruna Balmus ◽  
Alin Ciobica ◽  
Stefan Strungaru ◽  
Gabriel Plavan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Sleep Disturbances ◽  
Molecular Mechanisms ◽  
Disease Development ◽  
Scientific Database ◽  
Model Studies ◽  
Advantages And Disadvantages

The complex yet not fully understood pathophysiology of Parkinson’s disease includes an important molecular component consisting of oxidative status changes, thus leading to oxidative stress occurrence. While no particular evidence has been reported that describes the relationship between oxidative stress and the molecular mechanisms behind Parkinson’s disease development, animal model studies has shown that oxidative stress induction could modulate Parkinson’s disease symptomatology. Despite the inability to perfectly replicate human disease in animals and despite that Parkinson’s disease has not been reported in any animal species, animal modeling is one of the most important tools in understanding the complex mechanisms of human disorders. In this way, this study is aimed at detailing this particular relationship and describing the molecular mechanisms underlying Parkinson’s disease in animal models, focusing on the potential advantages and disadvantages of zebrafish in this context. The information relevant to this topic was gathered using major scientific database research (PubMed, Google Scholar, Web of Science, and Scopus) based on related keywords and inclusion criteria. Thus, it was observed that oxidative stress possesses an important role in Parkinson’s disease as shown by numerous animal model studies, many of which are based on rodent experimental models. However, an emerging impact of the zebrafish model was observed in the research of Parkinson’s disease pathological mechanisms with regard to disease development factors and the cause-effect relationship between oxidative stress and comorbidities (such as depression, hyposmia, fatigue, sleep disturbances, and cognitive deficits) and also with regard to the pharmacological potential of antioxidant molecules in Parkinson’s disease treatment.

scholarly journals Stem Derived Dopamine Neurons: Will They Replace DBS as the Leading Neurosurgical Treatment for Parkinson’s Disease?

2021 ◽  
pp. 1-9
Author(s):  
Roger A. Barker ◽  
Anders Björklund ◽  
Steven J. Frucht ◽  
Clive N. Svendsen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Stem Cell ◽  
Dopamine Neurons ◽  
Positive Outcomes ◽  
Critical Pathway ◽  
The Future ◽  
Neurosurgical Treatment

The use of stem cell derived dopamine neurons for treating patients with Parkinson’s disease has now evolved to the first in human clinical trials. In this debate, we argue that assuming these trials give positive outcomes that this therapy will supercede DBS as the neurosurgical treatment of choice for PD patients in the future given it is a one-off therapy that repairs a critical pathway in the parkinsonian brain.

scholarly journals Antioxidant Therapeutics in Parkinson’s Disease: Current Challenges and Opportunities

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 453
Author(s):  
Ana Patricia Duarte-Jurado ◽  
Yareth Gopar-Cuevas ◽  
Odila Saucedo-Cardenas ◽  
Maria de Jesus Loera-Arias ◽  
Roberto Montes-de-Oca-Luna ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Translational Medicine ◽  
Clinical Symptoms ◽  
Preclinical Studies ◽  
Enzymatic Antioxidants ◽  
Potential Treatment ◽  
Challenges And Opportunities ◽  
Therapeutic Molecules

Oxidative stress is considered one of the pathological mechanisms that cause Parkinson’s disease (PD), which has led to the investigation of several antioxidants molecules as a potential therapeutic treatment against the disease. Although preclinical studies have demonstrated the efficacy of these compounds to maintain neuronal survival and activity in PD models, these results have not been reflected in clinical trials, antioxidants have not been able to act as disease modifiers in terms of clinical symptoms. Translational medicine currently faces the challenge of redesigning clinical trials to standardize criteria when testing molecules to reduce responses’ variability. Herein, we discuss current challenges and opportunities regarding several non-enzymatic antioxidants’ therapeutic molecules for PD patients’ potential treatment.

scholarly journals GLP-1 and GIP receptor agonists in the treatment of Parkinson’s disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255726
Author(s):  
Carolina Vaccari ◽  
Denise Grotto ◽  
Tiago da V. Pereira ◽  
João Lauro V. de Camargo ◽  
Luciane C. Lopes
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Studies ◽  
Rating Scale ◽  
Cochrane Central Register ◽  
Preclinical Studies ◽  
Increased Risk

Background Parkinson’s disease (PD) is a progressive multifactorial neurodegenerative condition. Epidemiological studies have shown that patients with type 2 diabetes mellitus (T2DM2) are at increased risk for developing PD, indicating a possible insulin-modulating role in this latter condition. We hypothesized that drugs similar to glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP), used in the treatment of T2DM2, may play a role in PD. Objectives The purpose of this study is to systematically review and meta-analyze data of preclinical and clinical studies evaluating the efficacy and safety of GLP-1 and GIP drugs in the treatment of PD. Methods Two reviewers will independently evaluate the studies available in the Ovid Medline, Ovid Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cinahl, and Lilacs databases. Preclinical rodent or non-human primate studies and randomized controlled human clinical trials will be included, without language or publication period restrictions. Outcomes of interest in preclinical studies will be primarily locomotor improvements and adverse effects in animal models of PD. For clinical trials, we will evaluate clinical improvements rated by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale–parts I, II, III, and IV, and adverse effects. The risk of bias of preclinical studies will be assessed by the SYRCLE tool and CAMARADES checklist and the clinical studies by the Cochrane tool; the certainty of the evidence will be rated by GRADE. Discussion and conclusion There is an urge for new PD treatments that may slow the progression of the disease rather than just restoring dopamine levels. This study will comprehensively review and update the state of the art of what is known about incretin hormones and PD and highlight the strengths and limitations of translating preclinical data to the clinic whenever possible. Systematic review registration PROSPERO registration number CRD42020223435.

Molecular imaging of gene therapy. The future in Parkinson's disease therapy?

2005 ◽  
Vol 32 (S 4) ◽  
Author(s):  
A.H Jacobs ◽  
R Hilker ◽  
L Burghaus ◽  
W.D Heiss
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Molecular Imaging ◽  
Disease Therapy ◽  
The Future

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

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