[18F]F-DOPA Imaging in Patients With Autonomic Failure
Autonomic FailurePure Autonomic Failure3 moreAlpha-synucleinopathies refer to age-related neurodegenerative and dementing disorders, characterized by the accumulation of alpha-synuclein in neurons and/or glia. The anatomical location of alpha-synuclein inclusions (Lewy Bodies) and the pattern of progressive neuronal death (e.g. caudal to rostral brainstem) give rise to distinct neurological phenotypes, including Parkinson's disease (PD), Multiple System Atrophy (MSA), Dementia with Lewy Bodies (DLB). Common to these disorders are the involvement of the central and peripheral autonomic nervous system, where Pure Autonomic Failure (PAF) is thought (a) to be restricted to the peripheral autonomic system, and (b) a clinical risk factor for the development of a central synucleinopathy, and (c) an ideal model to assess biomarkers that predict phenoconversion to PD, MSA, or DLB. Such biomarkers would aid in clinical trial inclusion criteria to ensure assessments of disease- modifying strategies to, delay, or halt, the neurodegenerative process. One of these biomarkers may be related to the neurotransmitter dopamine (DA) and related changes in the substantia nigra (SN) and brainstem. [18F]F-DOPA is a radiolabeled substrate for aromatic amino acid decarboxylase (AAADC), an enzyme involved in the production of dopamine. Use of this radiolabeled substrate in positron emission tomography (PET) may provide insight to changes in monoamine production and how they relate to specific phenoconversions in PAF patients. Overall, this study aims to identify changes in dopamine production in key regions including the SN, locus coeruleus, and brainstem to distinguish between patients with PD, MSA, and DLB, which may provide vital information to predict conversion from peripheral to central nervous system disease.
A Phase 2 Study of ONO-2808 in Patients With Multiple System Atrophy
Multiple System Atrophy (MSA)This is a Phase 2, double-blind, parallel-group, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of multiple doses of ONO-2808 in patients with MSA. This is the first study of ONO-2808 in patients with MSA.
Pre-Gene Therapy Study in Parkinson's Disease and Multiple System Atrophy
Parkinson's DiseaseMultiple System Atrophy2 moreThe objective of this study is to describe disease progression in study participants diagnosed with early Parkinson's Disease or Multiple System Atrophy - Parkinsonian Type up to 18 months as delineated by clinical and biochemical parameters.
Pain and Autonomic Symptoms in Parkinson's Disease and Atypical Parkinsonisms
Parkinson DiseaseMultiple System AtrophyThe goal of this observational study is to learn about the impact of the different types of pain and of the domains involved in the autonomic disorders of inpatients and outpatients diagnosed with Parkinson disease (PD) and multiple system atrophy (MSA) admitted to Istituti Clinici Scientifici Maugeri Centers. The main aims are: Evaluate the prevalence of pain and characterize it in Parkinson's disease and atypical parkinsonisms (MSA) Evaluate the effect of rehabilitation on pain and autonomic symptoms Evaluate the prevalence of autonomic symptoms in Parkinson's disease and atypical parkinsonisms (MSA) Assess the impact of pain and autonomic symptoms on quality of life. Participants will perform neurological examination, rehabilitation program and clinical scales. Researchers will compare the two groups of patients (PD and MSA) and the effect of the rehabilitation on pain, autonomic symptoms and quality of life.
Facilitating Diagnostics and Prognostics of Parkinsonian Syndromes Using Neuroimaging
Parkinson DiseaseMultiple System Atrophy1 moreThe goals of this study are: 1) to identify biomarkers using neuroimaging that are associated with progression rate using statistical methods, and 2) to identify biomarkers that are associated with the differential diagnosis of Parkinson's disease and atypical parkinsonism.
Longitudinal Tracking of Patients Diagnosed With Neurodegenerative Movement Disorders
Neurodegenerative Diseasessca33 moreThe purpose of this protocol is to create an active natural history cohort of patients with degenerative movement disorders, tracked in a clinical setting with clinical rating scales and neuroimaging. The overarching rationale is that neurodegenerative diseases may be heterogeneous, complex disorders. A new way of performing clinical trials in these patients may be in order and this protocol aims to build a longitudinally tracked clinical trial-ready cohort of patients. The purpose of this protocol is to establish an active natural history cohort of patients with neurodegenerative movement disorders who are deeply phenotyped and "clinical trial ready" across Mass General Brigham. After a thorough clinical diagnostic evaluation (this may include clinically indicated testing, for example MRI, FDG-PET, MIBG scan, polysomnography, genetic testing, autonomic function tests, inflammatory tests, skin biopsy) the investigators aim to achieve this through: Longitudinal tracking of clinical progression through use of clinical scales including at the present time: UMSARS, BARS, MoCA and UPSIT, PROM, MDS-NMS, UPDRS, and SARA Longitudinal tracking of disease progression through use of neuroimaging including at the present time: TSPO-PET and 3D MRI (see section 1.3) This is a pilot study designed to track patients with neurodegenerative movement disorders across Mass General Brigham through MRI and PET imaging modalities and clinical measures. Figure 5 represents the study design in detail. In short, subjects will be asked to visit Mass General Brigham every 6-9 months over the course of 18 months for imaging and clinical evaluation.
Modifiable Variables in Parkinsonism (MVP)
Parkinson's DiseaseParkinsonism7 moreWe are trying to identify factors associated with improved quality of life and fewer PD symptoms. We are attempting to identify practices, beliefs, and therapies used by individuals who report excellent quality of life, few PD symptoms, and reduced rates of progression. After agreeing to participate, we will ask participants to fill our questionnaires about their experience with PD, their health in general, along with their food intake every six months for five years.
Neurodegenerative Diseases Registry
Neurodegenerative DiseasesParkinson Disease2 moreWith the increase in life expectancy of our population due to advancement of medical diagnosis and treatments, the incidence of age dependent neurodegenerative diseases increased, including Alzheimer's disease (AD), parkinsonian syndromes (PS), small vessel disease (SVD) and motor neuron disease (MND). In spite of the progress of knowing the pathogenesis of various neurodegenerative diseases at molecular and genetic level, they are still very incompletely understood and often cause diagnostic and therapeutic challenges to physicians. Due to the overlapping presentation and similar brain pathology, especially in the early stage of the diseases, it is difficult to differentiate idiopathic Parkinson's disease (iPD) from atypical parkinsonian syndromes, such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Similarly, distinguishing AD from other dementia syndromes including frontotemporal dementia (FTD), dementia with Lewy Bodies (DLB), corticobasal degeneration (CBD) and vascular dementia can be difficult. It is necessary to develop accurate and comprehensive diagnostic tests to properly prognosticate the diseases, start treatments in early stage of the diseases and maximize the accuracy of drug trials for more effective preventive and therapeutic measures for these neurodegenerative diseases. Therefore, the registry aims to generate a large database of cognitive, behavioral, lifestyle and psychological information of the subjects who suffered from neurodegenerative diseases, as well as to examine the genetic basis of neurodegenerative diseases to help decode the pathogenic mechanisms of the diseases. The registry may provide important information to understand symptom development of the neurodegenerative diseases, in which may help physicians to diagnose the diseases more accurately and provide better treatment plans.
Treatment of Transcranial Alternating Current Stimulation(tACS)on Cerebellar Ataxia
Spinocerebellar Ataxia Type 3Multiple System Atrophy-cerebellar TypeThis is a longitudinal, triple-blind, randomized-controlled, prospective observational study assessing patients with cerebellar ataxia, including spinocerebellar ataxia type 3 (SCA3) and multiple system atrophy-cerebellar type (MSA-C), to examine the efficacy, safety, and tolerability of transcranial alternating current stimulation (tACS) for up to 3 months.
Biomarkers in Parkinsonian Syndromes
Parkinsonian SyndromesParkinson's Disease2 moreParkinson disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are neurodegenerative disorders. PD and MSA are alpha-synucleinopathies, which are characterized by the abnormal accumulation of alpha-synuclein, while tau protein accumulates in PSP. The development of biological markers for the diagnosis and prognosis in PD, MSA and PSP remains an unmet need. Such biological markers are crucial for future disease-modification and neuroprotection trials. Alpha-synuclein has a high potential for biomarker development since it constitutes the pathological hallmark feature in PD and MSA. The oligomeric alpha-synuclein seems to be particularly involved in abnormal protein aggregation in alpha-synucleinopathies. The main objective is to compare oligomeric alpha-synuclein CSF levels between PD, MSA and PSP patients. PD and MSA patients will receive Cerebrospinal Fluid (CSF) and blood sampling at two study visits (baseline and after 12 months). Major secondary objectives are (i) to assess potential associations between the biomarker and clinical measures of disease severity and progression in MSA and PSP, and (ii) to assess the variation of the biomarker and its correlation to disease severity and progression in PD, MSA and PSP.