scholarly journals The Universal Prescription for Parkinson’s Disease: Exercise

2020 ◽  
Vol 10 (s1) ◽  
pp. S21-S27
Author(s):  
Jay L. Alberts ◽  
Anson B. Rosenfeldt
Keyword(s):  
Parkinson’S Disease ◽  
Heart Rate ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Aerobic Exercise ◽  
Animal Studies ◽  
Clinical Findings ◽  
Patient Specific ◽  
Functional Changes ◽  
Beneficial Effects

Over the past two decades, aerobic exercise has emerged as a mainstream recommendation to aid in treating Parkinson’s disease (PD). Despite the acknowledgement of the benefits of exercise for people with PD (PwPD), frequently, exercise recommendations lack specificity in terms of frequency, intensity and duration. Additionally, conflating physical activity with exercise has contributed to providing vague exercise recommendations to PwPD. Therefore, the beneficial effects of exercise may not be fully realized in PwPD. Data provided by animal studies and select human trials indicate aerobic exercise may facilitate structural and functional changes in the brain. Recently, several large human clinical trials have been completed and collectively support the use of aerobic exercise, specifically high-intensity aerobic exercise, in improving PD motor symptoms. Data from these and other studies provide the basis to include aerobic exercise as an integral component in treating PD. Based on positive clinical findings and trials, it is advised that PwPD perform aerobic exercise in the following dose: 3x/week, 30–40-minute main exercise set, 60–80% of heart rate reserve or 70–85% of heart rate max. In lieu of heart rate, individuals can achieve an intensity of 14–17 on a 20-point RPE scale. Ongoing clinical trials, SPARX3 and CYCLE-II, have potential to further develop patient-specific exercise recommendations through prognostic modeling.

scholarly journals Emulated Clinical Trials from Longitudinal Real-World Data Efficiently Identify Candidates for Neurological Disease Modification: Examples from Parkinson’s Disease

2020 ◽  
Author(s):  
Daphna Laifenfeld ◽  
Chen Yanover ◽  
Michal Ozery-Flato ◽  
Oded Shaham ◽  
Michal Rozen-Zvi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Real World ◽  
Late Onset ◽  
Real World Data ◽  
World Data ◽  
Healthcare Data ◽  
Beneficial Effects ◽  
Disease Modifying

AbstractReal-world healthcare data hold the potential to identify therapeutic solutions for progressive diseases by efficiently pinpointing safe and efficacious repurposing drug candidates. This approach circumvents key early clinical development challenges, particularly relevant for neurological diseases, concordant with the vision of the 21stCentury Cures Act. However, to-date, these data have been utilized mainly for confirmatory purposes rather than as drug discovery engines. Here, we demonstrate the usefulness of real-world data in identifying drug repurposing candidates for disease-modifying effects, specifically candidate marketed drugs that exhibit beneficial effects on Parkinson’s disease (PD) progression. We performed an observational study in cohorts of ascertained PD patients extracted from two large medical databases, Explorys SuperMart (N=88,867) and IBM MarketScan Research Databases (N=106,395); and applied two conceptually different, well-established causal inference methods to estimate the effect of hundreds of drugs on delaying dementia onset as a proxy for slowing PD progression. Using this approach, we identified two drugs that manifested significant beneficial effects on PD progression in both datasets: rasagiline, narrowly indicated for PD motor symptoms; and zolpidem, a psycholeptic. Each confers its effects through distinct mechanisms, which we explored via a comparison of estimated effects within the drug classification ontology. We conclude that analysis of observational healthcare data, emulating otherwise costly, large, and lengthy clinical trials, can highlight promising repurposing candidates, to be validated in prospective registration trials, for common, late-onset progressive diseases for which disease-modifying therapeutic solutions are scarce.

scholarly journals Aerobic Exercise and Healthy Nutrition as Neuroprotective Agents for Brain Health in Patients with Parkinson’s Disease: A Critical Review of the Literature

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 380
Author(s):  
Davide Maria Cammisuli ◽  
Ubaldo Bonuccelli ◽  
Simona Daniele ◽  
Claudia Martini ◽  
Jonathan Fusi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Aerobic Exercise ◽  
Cognitive Outcomes ◽  
Neuroprotective Agents ◽  
Brain Health ◽  
Beneficial Effects ◽  
Healthy Nutrition ◽  
Different Levels

Parkinson’s disease (PD) is characterized by motor and nonmotor features that have an influence on patients’ quality of life at different levels. To date, some evidences have arisen on the effectiveness of physical trainings and nutrients intake in ameliorating functional and cognitive outcomes in PD patients. Physical activity is effective in improving both motor and nonmotor features and recent epidemiological investigations have revealed the pivotal role that dietary patterns may play in reducing the risk of PD highlighting the pathogenesis of the neurodegeneration. Specifically, aerobic exercise shows beneficial effects in improving motor functions and executive control in PD patients, as well as proper nutrition may help in improving neuroprotective agents counteracting neurodegeneration and allows patients to better interact with the medication. Our narrative review critically focused on aerobic exercise and nutrition in PD in order to point out the best prescriptions for brain health of affected patients. Implications for a therapeutic plan and rehabilitation for these patients are also discussed.

scholarly journals Update on Dopamine Agonists in Parkinson's Disease: “Beyond Bromocriptine”

1987 ◽  
Vol 14 (S3) ◽  
pp. 474-482 ◽  
Author(s):  
Anthony E. Lang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Dopamine Agonists ◽  
Infusion Therapy ◽  
Foreseeable Future ◽  
Phase 3 ◽  
Beneficial Effects ◽  
Elderly Humans ◽  
Ergot Derivative

ABSTRACT:Since the initiation of bromocriptine therapy for Parkinson's disease several newer dopamine agonists have been developed. Pergolide has reached the stage of Phase 3 clinical trials and will probably be available for general use sometime in the foreseeable future. Lisuride shows most promise in its parenteral form for infusion therapy of patients with severe fluctuations. Mesulergine, another ergot-derivative and ciladopa, a new non-ergot agonist, have been withdrawn from further clinical use due to tumorogenesis in rats. It is questionable how applicable these findings are to the use of the drugs in elderly humans with parkinsonism. Recently a small number of drugs have been found to have postsynaptic dopamine agonist properties only in the setting of denervated supersensitive dopamine receptors. These agents may be particularly effective in the early treatment of patients with Parkinson's disease. This paper will review a number of the dopamine agonists which have been developed since the introduction of bromocriptine therapy. Several of these have shown beneficial effects in early clinical trials while others show promise in preclinical studies of animal models of parkinsonism.

scholarly journals Emulated Clinical Trials from Longitudinal Real-World Data Efficiently Identify Candidates for Neurological Disease Modification: Examples from Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Daphna Laifenfeld ◽  
Chen Yanover ◽  
Michal Ozery-Flato ◽  
Oded Shaham ◽  
Michal Rosen-Zvi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Real World ◽  
Late Onset ◽  
Real World Data ◽  
World Data ◽  
Healthcare Data ◽  
Beneficial Effects ◽  
Disease Modifying

Real-world healthcare data hold the potential to identify therapeutic solutions for progressive diseases by efficiently pinpointing safe and efficacious repurposing drug candidates. This approach circumvents key early clinical development challenges, particularly relevant for neurological diseases, concordant with the vision of the 21st Century Cures Act. However, to-date, these data have been utilized mainly for confirmatory purposes rather than as drug discovery engines. Here, we demonstrate the usefulness of real-world data in identifying drug repurposing candidates for disease-modifying effects, specifically candidate marketed drugs that exhibit beneficial effects on Parkinson’s disease (PD) progression. We performed an observational study in cohorts of ascertained PD patients extracted from two large medical databases, Explorys SuperMart (N = 88,867) and IBM MarketScan Research Databases (N = 106,395); and applied two conceptually different, well-established causal inference methods to estimate the effect of hundreds of drugs on delaying dementia onset as a proxy for slowing PD progression. Using this approach, we identified two drugs that manifested significant beneficial effects on PD progression in both datasets: rasagiline, narrowly indicated for PD motor symptoms; and zolpidem, a psycholeptic. Each confers its effects through distinct mechanisms, which we explored via a comparison of estimated effects within the drug classification ontology. We conclude that analysis of observational healthcare data, emulating otherwise costly, large, and lengthy clinical trials, can highlight promising repurposing candidates, to be validated in prospective registration trials, beneficial against common, late-onset progressive diseases for which disease-modifying therapeutic solutions are scarce.

scholarly journals Failure of Glial Cell-Line Derived Neurotrophic Factor (GDNF) in Clinical Trials Orchestrated By Reduced NR4A2 (NURR1) Transcription Factor in Parkinson’s Disease. A Systematic Review

2021 ◽  
Vol 13 ◽  
Author(s):  
Piniel Alphayo Kambey ◽  
Kouminin Kanwore ◽  
Abiola Abdulrahman Ayanlaja ◽  
Iqra Nadeem ◽  
YinZhen Du ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Cell Line ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Clinical Findings ◽  
Related Factor ◽  
Promising Therapeutic Target ◽  
Neuro Protection

Parkinson’s disease (PD) is one of the most common neurodegenerative maladies with unforeseen complex pathologies. While this neurodegenerative disorder’s neuropathology is reasonably well known, its etiology remains a mystery, making it challenging to aim therapy. Glial cell-line derived neurotrophic factor (GDNF) remains an auspicious therapeutic molecule for treating PD. Neurotrophic factor derived from glial cell lines is effective in rodents and nonhuman primates, but clinical findings have been equivocal. Laborious exertions have been made over the past few decades to improve and assess GDNF in treating PD (clinical studies). Definitive clinical trials have, however, failed to demonstrate a survival advantage. Consequently, there seemed to be a doubt as to whether GDNF has merit in the potential treatment of PD. The purpose of this cutting edge review is to speculate as to why the clinical trials have failed to meet the primary endpoint. We introduce a hypothesis, “Failure of GDNF in clinical trials succumbed by nuclear receptor-related factor 1 (Nurr1) shortfall.” We demonstrate how Nurr1 binds to GDNF to induce dopaminergic neuron synthesis. Due to its undisputable neuro-protection aptitude, we display Nurr1 (also called Nr4a2) as a promising therapeutic target for PD.

scholarly journals Personalised Advanced Therapies in Parkinson’s Disease: The Role of Non-Motor Symptoms Profile

2021 ◽  
Vol 11 (8) ◽  
pp. 773
Author(s):  
Valentina Leta ◽  
Haidar S. Dafsari ◽  
Anna Sauerbier ◽  
Vinod Metta ◽  
Nataliya Titova ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Patient Specific ◽  
Motor Symptoms ◽  
Exclusion Criteria ◽  
Subcutaneous Infusion ◽  
Beneficial Effects ◽  
Advanced Therapies ◽  
Non Motor Symptoms

Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson’s disease (PD). Currently, selection of device-aided therapies is mainly focused on patients’ motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications. In this viewpoint, we suggest that specific non-motor symptoms could be used as an additional anchor to motor symptoms and not merely as exclusion criteria to deliver bespoke and patient-specific personalised therapy for advanced PD.

scholarly journals The Effects of Medicinal Plants and Bioactive Natural Compounds on Homocysteine

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3081
Author(s):  
Mohammad Amin Atazadegan ◽  
Mohammad Bagherniya ◽  
Gholamreza Askari ◽  
Aida Tasbandi ◽  
Amirhossein Sahebkar
Keyword(s):  
Clinical Trials ◽  
Medicinal Plants ◽  
Vascular Endothelium ◽  
Animal Studies ◽  
Natural Compounds ◽  
Herbal Products ◽  
Mortality And Morbidity ◽  
Beneficial Effects ◽  
Serum Homocysteine ◽  
Prevention And Treatment

Background: Among non-communicable diseases, cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity in global communities. By 2030, CVD-related deaths are projected to reach a global rise of 25 million. Obesity, smoking, alcohol, hyperlipidemia, hypertension, and hyperhomocysteinemia are several known risk factors for CVDs. Elevated homocysteine is tightly related to CVDs through multiple mechanisms, including inflammation of the vascular endothelium. The strategies for appropriate management of CVDs are constantly evolving; medicinal plants have received remarkable attention in recent researches, since these natural products have promising effects on the prevention and treatment of various chronic diseases. The effects of nutraceuticals and herbal products on CVD/dyslipidemia have been previously studied. However, to our knowledge, the association between herbal bioactive compounds and homocysteine has not been reviewed in details. Thus, the main objective of this study is to review the efficacy of bioactive natural compounds on homocysteine levels according to clinical trials and animal studies. Results: Based on animal studies, black and green tea, cinnamon, resveratrol, curcumin, garlic extract, ginger, and soy significantly reduced the homocysteine levels. According to the clinical trials, curcumin and resveratrol showed favorable effects on serum homocysteine. In conclusion, this review highlighted the beneficial effects of medicinal plants as natural, inexpensive, and accessible agents on homocysteine levels based on animal studies. Nevertheless, the results of the clinical trials were not uniform, suggesting that more well-designed trials are warranted.

scholarly journals Bringing Advanced Therapies for Parkinson’s Disease to the Clinic: The Scientist’s Perspective

2021 ◽  
pp. 1-6
Author(s):  
Mark Tomishima ◽  
Agnete Kirkeby
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Phase I Clinical Trials ◽  
Preclinical Models ◽  
Preclinical Development ◽  
Dopaminergic Medication ◽  
Gene Therapies ◽  
Advanced Therapies ◽  
New Phase

After many years of preclinical development, cell and gene therapies have advanced from research tools in the lab to clinical-grade products for patients, and today they constitute more than a quarter of all new Phase I clinical trials for Parkinson’s disease. Whereas efficacy has been convincingly proven for many of these products in preclinical models, the field is now entering a new phase where the functionality and safety of these products will need to stand the test in clinical trials. If successful, these new products can have the potential to provide patients with a one-time administered treatment which may alleviate them from daily symptomatic dopaminergic medication.

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