28 research outputs found
Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis
No full textVarious forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough.LMN
Research Priorities on the Role of α‐ Synuclein in Parkinson's Disease Pathogenesis
No full textAbstract Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α‐synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease‐modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Impact of the COVID-19 Pandemic on Parkinson's Disease and Movement Disorders
No full textHuman coronaviruses have classically caused mild respiratory infections. Two previous outbreaks caused by newly identified coronaviruses, SARS-CoV in 2002 and MERS-CoV in 2012, caused serious respiratory disease with increased mortality. The current coronavirus disease 2019 (COVID-19) pandemic is caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).The infection originated late 2019 in China, and in a few months disseminated to reach almost 200 countries, now affecting over 500,000 people with an overall estimated mortality of 4% (World Health Organization; March 27, 2020)
Ethical Issues in Scientific Research in Developing Countries
No full textEthics is a cornerstone of dental research, and, for that matter, any research. Authorship in scientific research is an important issue which requires considerable discussion and debate. The pressure to publish is well-established in the university community. Faculty member’s performance and promotion are judged by the number of published articles in academic or scholarly journals. Most of the dental schools or universities in India do not have an ethics committee. Ethical issues like informed consent and ethics committee clearance are being taken for granted. That is, these words are mentioned in the manuscript or research paper, without the actual consent or clearance being given. The authors submit that these infringements may be made knowingly and/or unknowingly. The misconduct in research and publication not only affects other authors, but reviewers and editors, as well. However, the worst sufferer is the patient
Research Priorities on the Role of α‐Synuclein in Parkinson's Disease Pathogenesis
No full textInternational audienceVarious forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Deep brain stimulation: preoperative issues.
No full textInternational audienceNumerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making
Research Priorities on the Role of α-Synuclein in Parkinson\u27s Disease Pathogenesis
No full text\ua9 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Various forms of Parkinson\u27s disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, despite vast research efforts of more than a quarter century. A better understanding of the role of αSyn, either primary or secondary, is critical for developing disease-modifying therapies. Previous attempts to hone this research have been challenged by experimental limitations, but recent technological advances may facilitate progress. The Scientific Issues Committee of the International Parkinson and Movement Disorder Society (MDS) charged a panel of experts in the field to discuss current scientific priorities and identify research strategies with potential for a breakthrough. \ua9 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
The Management of Parkinson's Disease Before, during and after Pregnancy - an MDS Scientific Issues Committee Review
No full textTreatment Selection and Prioritization for the EJS ACT-PD MAMS Trial Platform
No full textBackgroundThere are currently no disease-modifying therapies (DMTs) registered for Parkinson's disease (PD). The Edmond J. Safra Accelerating Clinical Trials in Parkinson Disease (EJS ACT-PD) initiative will expedite clinical assessment of putative DMTs through a multi-arm multistage (MAMS) trial, testing several treatments against a common placebo arm and replacing unsuccessful therapies early. ObjectiveThe objective of this study was to describe the treatment selection process for the EJS ACT-PD clinical trial platform. MethodsA Treatment Selection Working Group (TSWG) identified compounds using complementary strategies, such as literature search, related initiatives (Cure Parkinson's International Linked Clinical Trials [iLCT] initiative), and expert suggestions. Compounds were classified into five mechanistic subgroups (mitochondrial, lysosomal, protein, inflammation, “other”). “Go/No-Go” criteria and a scoring system covering preclinical, pharmacological, and clinical evidence were devised. Experts scored the candidates for quantitative rankings. Dossiers adapted from iLCT documents were produced for the top-ranked compounds and in turn prioritized by the TSWG. Practical and logistical considerations from the Steering Committee (SC) guided the final decision. Patient and Public Involvement and Engagement representatives provided feedback throughout the process. ResultsA total of 293 interventions were identified, 52 of which passed the “Go/No-Go” criteria and were scored. Dossiers of the 14 top-ranked compounds were submitted to the SC. Telmisartan, terazosin, and ursodeoxycholic acid were selected as the initial interventions. ConclusionsDrug selection in DMT PD MAMS trials requires consideration of scientific and practical issues. We present a robust system that can inform similar initiatives.</p
RESTORATION OF MOTOR AND NON-MOTOR FUNCTIONS BY NEUROTROPHIC FACTORS IN NONHUMAN PRIMATES WITH DOPAMINE DEPLETION
No full textParkinson’s disease (PD) is a progressive debilitating neurodegenerative disorder characterized by resting tremor, rigidity, bradykinesia and postural instability. As the disease progresses there is a loss of dopamine (DA) neurons in the substantia nigra projecting to the various forebrain and sub-cortical regions. Current treatments for PD are unable to prevent or curtail the neurodegenerative process; so rescuing remaining dopamine in the mid-brain has been the recent focus of research examining the effectiveness of neurotrophic factors (NTFs) in the treatment of PD. In this dissertation, the ability of three novel, recently discovered NTFs to restore DA neurons and motor function in a nonhuman primate model of PD was examined. The NTFs were Cerebral Dopamine Neurotrophic Factor (CDNF) and two variants of Neurturin (NRTN), N2 and N4, that have mutations that prevent binding to heparin sulfate binding sites in the brain. These studies used the unilateral low dose (0.15 ± 0.001 mg/kg) monkey 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD to cause loss of DA neurons. Six groups of monkeys were studied: vehicle-treated (negative control), Glial Cell-line Derived Neurotropic Factor (GDNF, positive control), two groups of CDNF-treated monkeys (450 μg and 150 μg), and N2 and N4-treated groups. After MPTP, monkeys developed moderate symptoms of PD (PD rating scale score=7.9±0.5 on a scale of 0-22, p<0.001), motor dysfunction and increased daytime sleepiness. After three months of infusions, all three NTFs (150 μg CDNF, N2 and N4) significantly increased the number of DA neurons in the substantia nigra, p=0.03, and improved parkinsonian symptoms measured by rating scale, p<0.001. Most motor functions were significantly correlated with the number of DA neurons in the substantia nigra. N4 significantly improved daytime sleep duration, bouts and wake-latency (p=0.02, p=0.06 and p=0.02, respectively). In summary, CDNF, N2 and N4 trophic factors are neurorestorative to DA neurons, motor function is tightly correlated with DA neuronal number, and N4 improved the non-motor symptom of increased daytime sleepiness in this monkey PD model. These factors hold promise for clinical therapy for PD patients
