Promising disease-modifying therapies for Parkinson’s disease

2019 ◽  
Vol 11 (520) ◽  
pp. eaba1659 ◽  
Author(s):  
Valina L. Dawson ◽  
Ted M. Dawson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
New Agents ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Disease Modifying

To date, there is no disease-modifying therapy for Parkinson’s disease; however, promising new agents have advanced into clinical trials.

scholarly journals Nigral Iron Elevation Is an Invariable Feature of Parkinson’s Disease and Is a Sufficient Cause of Neurodegeneration

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Scott Ayton ◽  
Peng Lei
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Neurodegenerative Disorder ◽  
Motor Deficits ◽  
Disease Mechanism ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Sufficient Cause ◽  
Disease Modifying

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor deficits accompanying degeneration of substantia nigra pars compactor (SNc) neurons. Although familial forms of the disease exist, the cause of sporadic PD is unknown. Symptomatic treatments are available for PD, but there are no disease modifying therapies. While the neurodegenerative processes in PD may be multifactorial, this paper will review the evidence that prooxidant iron elevation in the SNc is an invariable feature of sporadic and familial PD forms, participates in the disease mechanism, and presents as a tractable target for a disease modifying therapy.

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 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.

Multitarget disease-modifying therapy in Parkinson's disease?

2015 ◽  
Vol 14 (10) ◽  
pp. 975-976 ◽  
Author(s):  
Paolo Calabresi ◽  
Massimiliano Di Filippo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Modifying Therapy ◽  
Disease Modifying

Immune system and new avenues in Parkinson’s disease research and treatment

2019 ◽  
Vol 30 (7) ◽  
pp. 709-727 ◽  
Author(s):  
Ava Nasrolahi ◽  
Fatemeh Safari ◽  
Mehdi Farhoudi ◽  
Afra Khosravi ◽  
Fereshteh Farajdokht ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Loss ◽  
Disease Research ◽  
Disease Modifying Therapies ◽  
Progressive Neurodegeneration ◽  
Disease Modifying ◽  
Clinical Description ◽  
Genetic And Environmental Factors

Abstract Parkinson’s disease (PD) is a progressive neurological disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. However, although 200 years have now passed since the primary clinical description of PD by James Parkinson, the etiology and mechanisms of neuronal loss in this disease are still not fully understood. In addition to genetic and environmental factors, activation of immunologic responses seems to have a crucial role in PD pathology. Intraneuronal accumulation of α-synuclein (α-Syn), as the main pathological hallmark of PD, potentially mediates initiation of the autoimmune and inflammatory events through, possibly, auto-reactive T cells. While current therapeutic regimens are mainly used to symptomatically suppress PD signs, application of the disease-modifying therapies including immunomodulatory strategies may slow down the progressive neurodegeneration process of PD. The aim of this review is to summarize knowledge regarding previous studies on the relationships between autoimmune reactions and PD pathology as well as to discuss current opportunities for immunomodulatory therapy.

scholarly journals Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease

Science ◽  
2018 ◽  
Vol 362 (6414) ◽  
pp. eaat8407 ◽  
Author(s):  
Tae-In Kam ◽  
Xiaobo Mao ◽  
Hyejin Park ◽  
Shih-Ching Chou ◽  
Senthilkumar S. Karuppagounder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Parp Inhibitors ◽  
Dopamine Neurons ◽  
Parp Activation ◽  
Disease Modifying Therapy ◽  
Genetic Deletion ◽  
Disease Modifying ◽  
Parp 1

The pathologic accumulation and aggregation of α-synuclein (α-syn) underlies Parkinson’s disease (PD). The molecular mechanisms by which pathologic α-syn causes neurodegeneration in PD are not known. Here, we found that pathologic α-syn activates poly(adenosine 5′-diphosphate–ribose) (PAR) polymerase-1 (PARP-1), and PAR generation accelerates the formation of pathologic α-syn, resulting in cell death via parthanatos. PARP inhibitors or genetic deletion of PARP-1 prevented pathologic α-syn toxicity. In a feed-forward loop, PAR converted pathologic α-syn to a more toxic strain. PAR levels were increased in the cerebrospinal fluid and brains of patients with PD, suggesting that PARP activation plays a role in PD pathogenesis. Thus, strategies aimed at inhibiting PARP-1 activation could hold promise as a disease-modifying therapy to prevent the loss of dopamine neurons in PD.

Sign in / Sign up

Export Citation Format

Share Document