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.

scholarly journals Implications of dopaminergic medication withdrawal in Parkinson’s disease

2021 ◽  
Author(s):  
J. Koschel ◽  
K. Ray Chaudhuri ◽  
L. Tönges ◽  
M. Thiel ◽  
V. Raeder ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Medication ◽  
Medication Withdrawal

scholarly journals Restoration of Noradrenergic Function in Parkinson’s Disease Model Mice

ASN NEURO ◽  
2021 ◽  
Vol 13 ◽  
pp. 175909142110097
Author(s):  
Kui Cui ◽  
Fan Yang ◽  
Turan Tufan ◽  
Muhammad U. Raza ◽  
Yanqiang Zhan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factors ◽  
Disease Model ◽  
Neuronal Loss ◽  
Mrna Levels ◽  
Gene Therapies ◽  
Protein Levels ◽  
Dopaminergic Systems ◽  
And Function

Dysfunction of the central noradrenergic and dopaminergic systems is the primary neurobiological characteristic of Parkinson’s disease (PD). Importantly, neuronal loss in the locus coeruleus (LC) that occurs in early stages of PD may accelerate progressive loss of dopaminergic neurons. Therefore, restoring the activity and function of the deficient noradrenergic system may be an important therapeutic strategy for early PD. In the present study, the lentiviral constructions of transcription factors Phox2a/2b, Hand2 and Gata3, either alone or in combination, were microinjected into the LC region of the PD model VMAT2 Lo mice at 12 and 18 month age. Biochemical analysis showed that microinjection of lentiviral expression cassettes into the LC significantly increased mRNA levels of Phox2a, and Phox2b, which were accompanied by parallel increases of mRNA and proteins of dopamine β-hydroxylase (DBH) and tyrosine hydroxylase (TH) in the LC. Furthermore, there was considerable enhancement of DBH protein levels in the frontal cortex and hippocampus, as well as enhanced TH protein levels in the striatum and substantia nigra. Moreover, these manipulations profoundly increased norepinephrine and dopamine concentrations in the striatum, which was followed by a remarkable improvement of the spatial memory and locomotor behavior. These results reveal that over-expression of these transcription factors in the LC improves noradrenergic and dopaminergic activities and functions in this rodent model of PD. It provides the necessary groundwork for the development of gene therapies of PD, and expands our understanding of the link between the LC-norepinephrine and dopamine systems during the progression of PD.

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

scholarly journals Influence of Dopaminergic Medication on Conditioned Pain Modulation in Parkinson's Disease Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0135287 ◽  
Author(s):  
Wiebke Grashorn ◽  
Odette Schunke ◽  
Carsten Buhmann ◽  
Katarina Forkmann ◽  
Sabrina Diedrich ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pain Modulation ◽  
Conditioned Pain Modulation ◽  
Dopaminergic Medication

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.

Longitudinal Change and Progression Indicators Using the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale in Two Independent Cohorts with Early Parkinson’s Disease

2021 ◽  
pp. 1-16
Author(s):  
Michael Bartl ◽  
Mohammed Dakna ◽  
Sebastian Schade ◽  
Tamara Wicke ◽  
Elisabeth Lang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Rating Scale ◽  
De Novo ◽  
Longitudinal Change ◽  
Single Center ◽  
Square Roots ◽  
Disease Rating

Background: The MDS-Unified Parkinson’s disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items. Objective: To systematically dissect MDS-UPDRS to predict PD progression. Methods: 574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling. Results: Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values. Conclusion: Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials.

scholarly journals The Qualification of an Enrichment Biomarker for Clinical Trials Targeting Early Stages of Parkinson’s Disease

2019 ◽  
Vol 9 (3) ◽  
pp. 553-563 ◽  
Author(s):  
Diane Stephenson ◽  
Derek Hill ◽  
Jesse M. Cedarbaum ◽  
Maria Tome ◽  
Spiros Vamvakas ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Trials ◽  
Early Stages
Sign in / Sign up

Export Citation Format

Share Document