Initial and disease-modifying strategies in Parkinson’s disease

2013 ◽  
pp. 23-41
Author(s):  
Lawrence W Elmer ◽  
Robert A Hauser
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Modifying

Phosphodiesterase 10 Inhibitors: New Disease Modifying Drugs for Parkinson’s Disease?

2014 ◽  
Vol 21 (10) ◽  
pp. 1171-1187 ◽  
Author(s):  
A.M. Garcia ◽  
M. Redondo ◽  
A. Martinez ◽  
C. Gil
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
New Disease ◽  
Disease Modifying Drugs ◽  
Disease Modifying

scholarly journals Exenatide once weekly over 2 years as a potential disease-modifying treatment for Parkinson’s disease: protocol for a multicentre, randomised, double blind, parallel group, placebo controlled, phase 3 trial: The ‘Exenatide-PD3’ study

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e047993
Author(s):  
Nirosen Vijiaratnam ◽  
Christine Girges ◽  
Grace Auld ◽  
Marisa Chau ◽  
Kate Maclagan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Outcome ◽  
Phase 3 ◽  
Double Blind ◽  
Treatment Groups ◽  
Link Type ◽  
South Central ◽  
Disease Modifying ◽  
Secondary Outcomes

IntroductionParkinson’s disease (PD) is a common neurodegenerative disorder with substantial morbidity. No disease-modifying treatments currently exist. The glucagon like peptide-1 receptor agonist exenatide has been associated in single-centre studies with reduced motor deterioration over 1 year. The aim of this multicentre UK trial is to confirm whether these previous positive results are maintained in a larger number of participants over 2 years and if effects accumulate with prolonged drug exposure.Methods and analysisThis is a phase 3, multicentre, double-blind, randomised, placebo-controlled trial of exenatide at a dose of 2 mg weekly in 200 participants with mild to moderate PD. Treatment duration is 96 weeks. Randomisation is 1:1, drug to placebo. Assessments are performed at baseline, week 12, 24, 36, 48, 60, 72, 84 and 96 weeks.The primary outcome is the comparison of Movement Disorders Society Unified Parkinson’s Disease Rating Scale part 3 motor subscore in the practically defined OFF medication state at 96 weeks between participants according to treatment allocation. Secondary outcomes will compare the change between groups among other motor, non-motor and cognitive scores. The primary outcome will be reported using descriptive statistics and comparisons between treatment groups using a mixed model, adjusting for baseline scores. Secondary outcomes will be summarised between treatment groups using summary statistics and appropriate statistical tests to assess for significant differences.Ethics and disseminationThis trial has been approved by the South Central-Berkshire Research Ethics Committee and the Health Research Authority. Results will be disseminated in peer-reviewed journals, presented at scientific meetings and to patients in lay-summary format.Trial registration numbersNCT04232969, ISRCTN14552789.

Identifying drugs with disease‐modifying potential in Parkinson's disease using artificial intelligence and pharmacoepidemiology

2020 ◽  
Vol 29 (8) ◽  
pp. 864-872
Author(s):  
Laura C. Maclagan ◽  
Naomi P. Visanji ◽  
Yi Cheng ◽  
Mina Tadrous ◽  
Alix M. B. Lacoste ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Modifying

scholarly journals A Preclinical Systematic Review of Ginsenoside-Rg1 in Experimental Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Liang Song ◽  
Meng-Bei Xu ◽  
Xiao-Li Zhou ◽  
Dao-pei Zhang ◽  
Shu-ling Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Quality Score ◽  
Control Group ◽  
Rotarod Test ◽  
Neuroprotective Effects ◽  
Disease Modifying ◽  
Antioxidant Stress ◽  
Th Mrna

To date, no drug has been proven to be neuroprotective or disease-modifying for Parkinson’s disease (PD) in clinical trials. Here, we aimed to assess preclinical evidence of Ginsenosides-Rg1 (G-Rg1), a potential neuroprotectant, for experimental PD and its possible mechanisms. Eligible studies were identified by searching six electronic databases from their inception to August 2016. Twenty-five eligible studies involving 516 animals were identified. The quality score of these studies ranged from 3 to 7. Compared with the control group, two out of the 12 studies of MPTP-induced PD showed significant effects of G-Rg1 for improving the rotarod test (P<0.01), two studies for improving the swim-score values (P<0.01), six studies for improving the level of TH protein expression (P<0.01), and two studies for increasing the expression of TH mRNA in the substantia nigra of mice (P<0.01). The studies reported that G-Rg1 exerted potential neuroprotective effects on PD model through different mechanisms as antineuroinflammatory activities (n=10), antioxidant stress (n=3), and antiapoptosis (n=11). In conclusion, G-Rg1 exerted potential neuroprotective functions against PD largely by antineuroinflammatory, antioxidative, and antiapoptotic effects. G-Rg1 as a promising neuroprotectant for PD needs further confirmation by clinical trials.

scholarly journals Current disease modifying approaches to treat Parkinson’s disease

2015 ◽  
Vol 73 (7) ◽  
pp. 1365-1379 ◽  
Author(s):  
Dan Lindholm ◽  
Johanna Mäkelä ◽  
Valentina Di Liberto ◽  
Giuseppa Mudò ◽  
Natale Belluardo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Modifying

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 Emerging disease-modifying strategies targeting α-synuclein for the treatment of Parkinson's disease

2018 ◽  
Vol 175 (15) ◽  
pp. 3080-3089 ◽  
Author(s):  
Darren M O'Hara ◽  
Suneil K Kalia ◽  
Lorraine V Kalia
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Emerging Disease ◽  
Disease Modifying

Parkinson's Disease Genetics and Pathophysiology

2021 ◽  
Vol 44 (1) ◽  
pp. 87-108
Author(s):  
Gabriel E. Vázquez-Vélez ◽  
Huda Y. Zoghbi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Genetic Variants ◽  
Neurodegenerative Disorder ◽  
Disease Risk ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Disease Modifying ◽  
Common Neurodegenerative Disorder

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by degeneration of the substantia nigra pars compacta and by accumulation of α-synuclein in Lewy bodies. PD is caused by a combination of environmental factors and genetic variants. These variants range from highly penetrant Mendelian alleles to alleles that only modestly increase disease risk. Here, we review what is known about the genetics of PD. We also describe how PD genetics have solidified the role of endosomal, lysosomal, and mitochondrial dysfunction in PD pathophysiology. Finally, we highlight how all three pathways are affected by α-synuclein and how this knowledge may be harnessed for the development of disease-modifying therapeutics.

Selected natural and synthetic agents effective against Parkinson’s disease with diverse mechanisms

2021 ◽  
Vol 21 ◽  
Author(s):  
Hayrettin Ozan Gulcan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Dopamine Metabolism ◽  
Dopaminergic Agonists ◽  
Alternative Drug ◽  
Synthetic Agents ◽  
Disease Modifying

: Similar to other neurodegenerative diseases, Parkinson’s disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strategies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug discovery studies focus on targets involved in the progressive neurodegenerative character of PD. This study has aimed to present the pathophysiology of PD concomitant to the representation of drugs and promising molecules displaying activity against the validated and non-validated targets of PD.

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