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 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.

scholarly journals Methodological Issues in Randomized Clinical Trials for Prodromal Alzheimer's and Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Camila Henriques de Aquino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Clinical Symptoms ◽  
Clinical Stage ◽  
Protein Accumulation ◽  
Clinical Endpoints ◽  
Definition Of ◽  
Biomarker Research

Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative disorders, respectively. Both are proteinopathies with inexorable courses and no approved disease-modifying therapies. A substantial effort has been made to identify interventions that could slow down the progression of AD and PD; to date, with no success. The advances in biomarker research improved the identification of individuals at risk for these disorders before symptom onset, recognizing the pre-clinical stage, in which there is abnormal protein accumulation but no clinical symptoms of the disease, and the prodromal stage, in which mild symptoms are present but the clinical diagnostic criteria for disease cannot be fulfilled. The ability to detect pre-clinical and prodromal stages of these diseases has encouraged clinical trials for disease-modification at earlier phases, seeking to slow or prevent phenoconversion into clinical disease. Clinical trials at these stages have several challenges, such as the identification of the eligible population, the appropriate choice of biomarkers, the definition of clinical endpoints, the duration of follow-up, and the statistical analysis. This article aims to discuss some of the methodological challenges in the design of trials for pre-clinical and prodromal phases of AD and PD, to critically review the recent studies, and to discuss methodological approaches to mitigate these challenges in trial design.

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.

Parkinson’s puzzle

2012 ◽  
Vol 153 (52) ◽  
pp. 2060-2069 ◽  
Author(s):  
András Guseo
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Symptoms ◽  
Critical Factor ◽  
Unknown Origin ◽  
Symptomatic Improvement ◽  
Blue Green Algae ◽  
Clinical Observations ◽  
Degenerative Disorders ◽  
Local Cell

Parkinson’s disease is one of the most frequent progressive degenerative disorders with unknown origin of the nervous system. The commutation of the disease on Guam led to the discovery of a neurotoxin which was also found in other continents. This neurotoxin was identified in the common cyanobacteria (blue-green algae). Early clinical observations suggested some loose correlations with gastric and duodenal ulcer and Parkinson’s disease, while recent studies revealed a toxin, almost identical to that found in cyanobacteria in one strain of Helicobacter pylori, which proved to cause Parkinson like symptoms in animals. Therefore, it cannot be ruled out that there is a slowly progressive poisoning in Parkinson’s disease. The disease specific alpha-sinuclein inclusions can be found in nerve cells of the intestinal mucosa far before the appearance of clinical symptoms indicating that the disease may start in the intestines. These results are strengthened by the results of Borody’s fecal transplants, after which in Parkinson patients showed a symptomatic improvement. Based on these observations the Parkinson puzzle is getting complete. Although these observations are not evidence based, they may indicate a new way for basic clinical research, as well as a new way of thinking for clinicians. These new observations in psycho-neuro-immunology strengthen the fact that immunological factors may also play a critical factor facilitating local cell necrosis which may be influenced easily. Orv. Hetil., 2012, 153, 2060–2069.

scholarly journals The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 371
Author(s):  
Patrycja Pawlik ◽  
Katarzyna Błochowiak
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Diseases ◽  
Diagnostic Tool ◽  
Clinical Symptoms ◽  
Early Screening ◽  
Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

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.

Neuroprotective agents for clinical trials in Parkinson's disease: A systematic assessment

Neurology ◽  
2003 ◽  
Vol 60 (8) ◽  
pp. 1234-1240 ◽  
Author(s):  
B.M. Ravina ◽  
S.C. Fagan ◽  
R.G. Hart ◽  
C.A. Hovinga ◽  
D.D. Murphy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Neuroprotective Agents ◽  
Systematic Assessment

Parkinson's disease and convergence insufficiency: a mini-review

2021 ◽  
Vol 1 (3) ◽  
pp. 108-111
Author(s):  
Mashael Al-Namaeh
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Control Group ◽  
Healthy Controls ◽  
Inclusion Criteria ◽  
Medline Search ◽  
Convergence Insufficiency ◽  
Eye Examination ◽  
The Relationship

Background: A key manifestation of Parkinson’s disease (PD) is visual impairment. Cognitive impairment has been found to overlap with convergence insufficiency (CI) in patients with PD and is associated with significantly greater near point convergence (NPC) distance. Difficulty in reading and diplopia were the most common symptoms of CI in PD. The prevalence of CI is greater among patients with PD. Therefore, this study aimed to assess the relationship between PD and CI. Methods: Studies that had included data on CI, NPC, or both were selected by searching PubMed/MEDLINE and clinicaltrails.gov, without any timeline or language limitation. The following terms were used in PubMed/MEDLINE search: ‘Clinical Trials’, ‘Parkinson’s Disease’, and ‘Convergence Insufficiency’. For clinical trials.gov database, the terms ‘Parkinson’s Disease’, ‘Convergence Insufficiency’, and ‘Completed Studies’ were used. Only those studies with control subjects were included. PubMed/MEDLINE search yielded 1,563 articles, but no article was found in the clinical trails.gov search. Twelve articles met the inclusion criteria, among which nine articles were selected as they had data on CI or NPC distance (cm), and PD.   Results: Overall, there were 1,563 articles; among them, 12 articles met the inclusion criteria. Nine articles were selected based on their data concerning CI or NPC distance (cm) and PD. Relative to the control group, the PD group had high CI. In addition, PD group showed increase in NPC distance than the control group. Conclusions: These data suggest that the patients with PD had an increased likelihood of developing CI visual symptoms, and increased NPC distance than healthy controls. These findings indicate that regular eye examination is very important for patients with PD.

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