scholarly journals Is It Possible to Conduct a Multi-Arm Multi-Stage Platform Trial in Parkinson’s Disease: Lessons Learned from Other Neurodegenerative Disorders and Cancer

2020 ◽  
Vol 10 (2) ◽  
pp. 413-428 ◽  
Author(s):  
Marie-Louise Zeissler ◽  
Vivien Li ◽  
Mahesh K.B. Parmar ◽  
Camille Buchholz Carroll
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Lessons Learned ◽  
Multi Stage

scholarly journals Imaging Familial and Sporadic Neurodegenerative Disorders Associated with Parkinsonism

2021 ◽  
Author(s):  
David J. Brooks
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Lewy Body Dementia ◽  
Imaging Biomarkers ◽  
Imaging Findings ◽  
Subclinical Disease ◽  
Similarities And Differences ◽  
Potential Use

AbstractIn this paper, the structural and functional imaging changes associated with sporadic and genetic Parkinson’s disease and atypical Parkinsonian variants are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed, and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression is debated. Imaging changes associated with nonmotor complications of PD are presented. The similarities and differences in imaging findings in Lewy body dementia, Parkinson’s disease dementia, and Alzheimer’s disease are discussed.

scholarly journals Identification of sixteen novel candidate genes for late onset Parkinson’s disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Alessandro Gialluisi ◽  
Mafalda Giovanna Reccia ◽  
Nicola Modugno ◽  
Teresa Nutile ◽  
Alessia Lombardi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Candidate Genes ◽  
Rare Variants ◽  
Late Onset ◽  
High Specificity ◽  
Diagnostic Tools ◽  
Multi Stage ◽  
Whole Exome ◽  
Family Based

Abstract Background Parkinson’s disease (PD) is a neurodegenerative movement disorder affecting 1–5% of the general population for which neither effective cure nor early diagnostic tools are available that could tackle the pathology in the early phase. Here we report a multi-stage procedure to identify candidate genes likely involved in the etiopathogenesis of PD. Methods The study includes a discovery stage based on the analysis of whole exome data from 26 dominant late onset PD families, a validation analysis performed on 1542 independent PD patients and 706 controls from different cohorts and the assessment of polygenic variants load in the Italian cohort (394 unrelated patients and 203 controls). Results Family-based approach identified 28 disrupting variants in 26 candidate genes for PD including PARK2, PINK1, DJ-1(PARK7), LRRK2, HTRA2, FBXO7, EIF4G1, DNAJC6, DNAJC13, SNCAIP, AIMP2, CHMP1A, GIPC1, HMOX2, HSPA8, IMMT, KIF21B, KIF24, MAN2C1, RHOT2, SLC25A39, SPTBN1, TMEM175, TOMM22, TVP23A and ZSCAN21. Sixteen of them have not been associated to PD before, were expressed in mesencephalon and were involved in pathways potentially deregulated in PD. Mutation analysis in independent cohorts disclosed a significant excess of highly deleterious variants in cases (p = 0.0001), supporting their role in PD. Moreover, we demonstrated that the co-inheritance of multiple rare variants (≥ 2) in the 26 genes may predict PD occurrence in about 20% of patients, both familial and sporadic cases, with high specificity (> 93%; p = 4.4 × 10− 5). Moreover, our data highlight the fact that the genetic landmarks of late onset PD does not systematically differ between sporadic and familial forms, especially in the case of small nuclear families and underline the importance of rare variants in the genetics of sporadic PD. Furthermore, patients carrying multiple rare variants showed higher risk of manifesting dyskinesia induced by levodopa treatment. Conclusions Besides confirming the extreme genetic heterogeneity of PD, these data provide novel insights into the genetic of the disease and may be relevant for its prediction, diagnosis and treatment.

scholarly journals Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen Gasca-Salas ◽  
Beatriz Fernández-Rodríguez ◽  
José A. Pineda-Pardo ◽  
Rafael Rodríguez-Rojas ◽  
Ignacio Obeso ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Drug Delivery ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Neurodegenerative Disorders ◽  
Focused Ultrasound ◽  
Temporal Cortex ◽  
Clinical State ◽  
Cognitive Improvement ◽  
Bbb Opening

AbstractMR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.

scholarly journals Response to Telemedicine Visits From Patients With Parkinsonism During the COVID-19 Pandemic on Postvisit Surveys

2021 ◽  
Vol 8 ◽  
pp. 237437352199722
Author(s):  
Wissam Deeb ◽  
Christopher W Hess ◽  
Noheli Gamez ◽  
Bhavana Patel ◽  
Kathryn Moore ◽  
...  
Keyword(s):  
Older Adults ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorders ◽  
Tertiary Care ◽  
Specialty Clinic ◽  
Cognitive Limitations ◽  
Time Savings ◽  
Ease Of Access ◽  
Almost All

Parkinson’s disease and parkinsonism are common chronic neurodegenerative disorders that tend to affect older adults and cause physical and sometimes cognitive limitations. Given that these limitations could impact successful telemedicine use, we aimed to investigate the experiences of patients with parkinsonism using telemedicine during the COVID-19 pandemic. A 19-item survey was emailed to patients with parkinsonism following telemedicine visits at a single US tertiary care parkinsonism specialty clinic. Seventy-four individuals responded, out of 270 invitations sent. Almost two-thirds (61.6%) of the respondents were comfortable with using technology in general, and almost all were very satisfied with their telemedicine experience. The most commonly reported benefits included cost and travel savings, ease of access to a specialist, and time savings. Issues with technology and previsit instructions were the most commonly identified challenges (28%). Urgent implementation, due to the pandemic, of telemedicine care for patients with parkinsonism was feasible and well received. The challenges most commonly reported by patients could be potentially alleviated by better education and support.

scholarly journals The role of dopamine in the brain - lessons learned from Parkinson's disease

NeuroImage ◽  
2019 ◽  
Vol 190 ◽  
pp. 79-93 ◽  
Author(s):  
David Meder ◽  
Damian Marc Herz ◽  
James Benedict Rowe ◽  
Stéphane Lehéricy ◽  
Hartwig Roman Siebner
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lessons Learned ◽  
The Brain
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