Multiple System Atrophy

The primary objective of the trial is to describe the long-term safety and tolerability of TEV-56286 administered orally for the treatment of adult participants with Multiple System Atrophy (MSA). A secondary objective of the trial is to further describe the safety and tolerability of TEV-56286. The planned total duration of the trial is approximately 100 weeks.

This research is studying a supplement called tributyrin in people with Progressive Supranuclear Palsy (PSP) to learn about its safety and tolerability as a potential treatment. The goal of this research study is to see if a similar supplementation regimen and virtual testing is feasible for people with PSP.

With 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.

VISMEMO-PD is an observational pilot study aimed at investigating visuospatial memory in reaching space and topographical memory in navigational space in patients with Parkinson's disease and Parkinsonism. The protocol is based on the hypothesis that topographical memory may deteriorate before visuospatial memory, suggesting that navigational memory impairment could represent an early indicator of disease progression. The study will include 80 participants stratified into four groups: patients with mild Parkinson's disease, patients with moderate-advanced Parkinson's disease, patients with Parkinsonism, and healthy participants. Visuospatial memory will be assessed using the Corsi Block-tapping Test, while topographical memory will be assessed using the Walking Corsi Test. Walking motor patterns will be recorded using wearable inertial sensors from the MOVIT system, and visual exploration strategies will be assessed using a wearable Pupil Labs eye-tracking system. The integration of cognitive, motor, and eye-tracking measures may support the identification of early neuropsychological markers and the development of tailored neurorehabilitation pathways for individuals with Parkinson's disease and Parkinsonism.

This is an open-label, single-center, prospective, single-arm clinical study. The primary objective of this study is to evaluate the safety, tolerability, and preliminary efficacy of ALT001 in the treatment of patients with multiple system atrophy (MSA) in a real-world setting.

This goal of this observational study is to clarify the variations in the natural course of atypical parkinsonian syndromes (APS, including MSA, DLB, PSP, and CBD), such as the progression rate of motor and non-motor symptoms and characteristic imaging evolution patterns. Establish a comprehensive assessment framework for APS, and develop clinical and biological databases to identify biomarkers with early predictive value.

MARKERS-NDD is a prospective, observational, longitudinal study, which aims to collect data from patients affected by neurodegenerative diseases (NDD) followed longitudinally for routine examinations performed as part of normal clinical practice. Data collected from clinical evaluations, movement analysis, brain imaging, neuropsychological and electroencephalographic assessments, blood chemistry tests will be analysed to carry out statistical investigations and predictive analyses, also using artificial intelligence systems, which allow the identification of new early markers of diagnosis and prognosis of neurodegenerative diseases.

This phase I double-blind study focuses on the safety and feasibility of implanting autologous peripheral nerve tissue (PNT) into the substantia nigra area of the brain in persons who have been diagnosed with either Parkinson's disease (PD) or Multiple System Atrophy (MSA). 7 participants will be enrolled, with 4 participants receiving the graft and 3 receiving a sham surgery. Eligible participants will be early in their diagnosis with a lower burden of symptoms. Participants will be followed initially for one year after surgery.

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder characterized by autonomic dysfunction, parkinsonism, and cerebellar ataxia. Abnormal aggregation of alpha-synuclein is believed to play an important role in disease progression. The α-Syn H21 monoclonal antibody is designed to selectively bind pathological alpha-synuclein aggregates and may reduce their spread and related neuroinflammation. This single-center, prospective, exploratory study will evaluate the safety, tolerability, and preliminary efficacy of the α-Syn H21 monoclonal antibody in patients with MSA. Participants will receive intravenous infusions of H21 every 4 weeks for 3 doses and will be followed for 12 weeks. Clinical symptoms, laboratory tests, imaging findings, and adverse events will be assessed to determine whether H21 may provide clinical benefit and support future larger studies.

The objective of this study is to find a more objective and accurate way to assess the efficacy of the treatment for neurogenic orthostatic hypotension. For this purpose, the investigators will use an activity monitor to determine the amount of time patients spend in the upright position (standing and walking; upright time) during 1 week of placebo (a pill with no active ingredients) and 1 week of their regular medication for orthostatic hypotension (midodrine or atomoxetine at their usual doses). Total upright time (i.e. tolerance to standing and walking) will be compared between placebo and active treatment to test the hypothesis that it can be used to assess the efficacy of the treatment for orthostatic hypotension and whether this outcome is superior to the assessment of symptoms using validated questionnaires.

This clinical trial aims to evaluate whether individualized targeted repetitive transcranial magnetic stimulation (rTMS) can improve motor and non-motor symptoms in patients with parkinsonian disorders. The main question it aims to answer is: * Does individualized targeted rTMS alleviate symptoms of parkinsonian disorders? * Which clinical manifestations of parkinsonian syndromes are responsive to individualized targeted rTMS, and to what degree? Procedures: * Preparation (Screening) Participants will undergo clinical assessments, MRI, and EEG before the treatment. * Treatment (2 Weeks) Participants will receive a 10-day TMS treatment (once daily, Monday-Friday). Each treatment day takes approximately 3-4 hours. Participants need to keep stable medications and rehabilitation routines during this time. * Follow-up (10 Weeks) Participants will undergo follow-up assessments at the end of treatment and 10 weeks after treatment. Assessments include clinical scales, MRI, and EEG.

Synucleinopathies are a group of rare diseases associated with worsening neurological deficits and the abnormal accumulation of the protein α-synuclein in the nervous system. Onset is usually in late adulthood at age 50 or older. Usually, synucleinopathies present clinically with slowness of movement, coordination difficulties or mild cognitive impairment. Development of these features indicates that abnormal alpha-synuclein deposits have destroyed key areas of the brain involved in the control of movement or cognition. Patients with synucleinopathies and signs of CNS-deficits are frequently diagnosed with Parkinson disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA). However, accumulation of alpha-synuclein and death of nerve cells can also begin outside the brain in the autonomic nerves. In such cases, syncucleinopathies present first with symptoms of autonomic impairment (unexplained constipation, urinary difficulties, and sexual dysfunction). In rare cases, hypotension on standing (a disorder known as orthostatic hypotension) may be the only clinical finding. This "pre-motor" autonomic stage suggests that the disease process may not yet have spread to the brain. After a variable period of time, but usually within 5-years, most patients with abnormally low blood pressure on standing develop cognitive or motor abnormalities. This stepwise evolution indicates that the disease spreads from the body to the brain. Another indication of this spread is that acting out dreams (i.e., REM sleep behavior disorder, RBD) a problem that occurs when the lower part of the brain is affected, may also be the first noticeable sign of Parkinson disease. The purpose of this study is to document the clinical features and biological markers of patients with synucleinopathies and better understand how these disorders evolve over time. The study will involve following patients diagnosed with a synucleinopathy (PD/DLB and MSA) and those believed to be in the "pre-motor" stage (with isolated autonomic impairment and/or RBD). Through a careful series of follow-up visits to participating Centers, we will focus on finding biological clues that predict which patients will develop motor/cognitive problems and which ones have the resilience to keep the disease at bay preventing spread to the brain. We will also define the natural history of MSA - the most aggressive of the synucleinopathies.

Multiple system atrophy is a rare, rapidly progressive neurodegenerative disease characterized by variable combinations of parkinsonism, cerebellar ataxia, and autonomic dysfunction. Existing natural history studies from North America, Europe, and Japan suggest that clinical phenotypes and disease progression may differ across populations. However, comprehensive multicenter prospective data from Chinese patients with multiple system atrophy remain limited. This prospective multicenter registry study aims to describe the clinical characteristics, longitudinal progression, and outcomes of Chinese patients with multiple system atrophy, to identify factors associated with disease progression and prognosis, and to establish a longitudinal cohort for future biomarker validation and clinical trial design.

A Phase 2a Study of Foralumab Nasal in Patients with Multiple System Atrophy (MSA)

This prospective observational study aims to identify and preliminarily validate molecular biomarkers, including microRNAs and metabolites, for the early differentiation of Parkinson's disease (PD) from atypical parkinsonian syndromes (APS). The study will enroll up to 100 patients with PD, 50 patients with suspected APS, and 50 healthy controls. Participants will undergo clinical assessments and provide blood, urine, and stool samples at baseline and after 12-18 months of follow-up. Molecular analyses, including microRNA profiling, metabolomics, RNA sequencing (RNA-seq), and microbiome analysis, will be performed to identify disease-specific diagnostic signatures. The primary objective is to detect differences in molecular profiles among patients with PD, patients with APS, and healthy controls. Secondary objectives include evaluating the diagnostic accuracy of biomarker panels and assessing longitudinal changes in these biomarkers over time. Although participants will not receive direct therapeutic benefits, the study may contribute to the development of non-invasive tools for the early diagnosis and improved differentiation of parkinsonian disorders.

The primary objectives are to evaluate the safety and tolerability of multiple doses of ION464 administered via intrathecal (IT) injection (Part 1) and to evaluate the long-term safety and tolerability of ION464 (Part 2) in participants with multiple system atrophy (MSA). The secondary objectives are to evaluate the pharmacodynamic (PD) effect of ION464 on the level of a potential biomarker of target engagement (Parts 1 and 2) and to evaluate the pharmacokinetic (PK) profile of ION464 in serum (Part 1).

The purpose of this study is to investigate the effect of comprehensive swallowing rehabilitation in patients with multiple system atrophy.

This expanded access protocol is part of IND 32226 to evaluate efficacy and safety of multiple intravenous administrations of allogeneic HB-adMSCs for the treatment of Multiple System Atrophy for up to 7 adult patients who pass pre-screening and a completed screening. The subjects will receive 12 intravenous infusions of HB-adMSCs and 6 intrathecal injections of HB-adMSCs over the course of 44 weeks (1 infusion each month and 1 injection every other month).

The 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.

This multicenter post-trial access program is designed to provide ATH434 orally BID to eligible patients who completed Phase 2 studies ATH434-201 or ATH434-202, and who may benefit from this treatment according to the evaluation by their treating physicians.

The present study aims to conduct a randomized controlled trial to evaluate the efficacy and safety of 3-n-Butylphthalide (NBP) in improving symptoms in patients with Multiple System Atrophy (MSA). The main questions it aims to answer are: 1. To evaluate whether NBP soft capsules, compared with placebo, alleviates the major clinical symptoms in patients with MSA. 2. Whether NBP application is safe to treat patients with MSA. In this trial, NBP will be compared with placebo (similar soft capsule without effective component of NBP) to demonstrate if NBP can alleviates MSA symptoms Participants of ENMSA will: 1. Take NBP or Placebo three times a day for 6 months 2. Be served with clinical visit four times for follow-up and tests 3. Keep a diary of drug application and symptom changes

The Swedish BioFINDER 2 study is a new study that will launch in 2017 and extends the previous cohorts of BioFINDER 1 study (www.biofinder.se). BioFINDER 1 is used e.g. to characterize the role of beta-amyloid pathology in early diagnosis of Alzheimer's disease (AD) using amyloid-PET (18F-Flutemetamol) and Aβ analysis in cerebrospinal fluid samples. The BioFINDER 1 study has resulted in more than 40 publications during the last three years, many in high impact journals, and some the of the results have already had important implications for the diagnostic work-up patients with AD in the clinical routine practice. The original BioFINDER 1 cohort started to include participants in 2008. Since then there has been a rapid development of biochemical and neuroimaging technologies which enable novel ways to the study biological processes involved in Alzheimer's disease in living people. There has also been a growing interest in the earliest stages of AD and other neurodegenerative diseases. With the advent of new tau-PET tracers there is now an opportunity to elucidate the role of tau pathology in the pathogenesis of AD and other tauopathies. The Swedish BioFINDER 2 study has been designed to complement the BioFINDER 1 study and to e.g. address issues regarding the role of tau pathology in different dementias and in preclinical stages of different dementia diseases. Further, the clinical assessments and MRI methods have been further optimized compared to BioFINDER 1. Detailed assessments of motor aspects and dual task performance, which is part of a sub-study named Motor-ACT: "Motor aspects and activities in relation to cognitive decline and brain pathologies, has been added to further optimize assessment of motor function.

This study aims to learn about the effects of continuous positive airway pressure (CPAP) on people with autonomic failure and high blood pressure when lying down (supine hypertension) to determine if it can be used to treat their high blood pressure during the night. CPAP (a widely used treatment for sleep apnea) involves using a machine that blows air into a tube connected to a mask covering the nose, or nose and mouth, to apply a low air pressure in the airways. The study includes 3-5 days spent in the Vanderbilt Clinical Research Center (CRC): at least one day of screening tests, followed by up to 3 study days. Subjects may be able to participate in daytime and/or overnight studies. The Daytime study consists of 2 study days: one with active CPAP and one with sham CPAP applied for up to 2 hours. The Overnight study consists of 3 study nights: one with active CPAP, one with sham CPAP, both applied for up to 9 hours and one night sleeping with the bed tilted head-up.

Alpha-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.

The goal of this observational cohort studyis to establish a high-quality clinical cohort of Parkinson's disease (PD) and multiple system atrophy (MSA) patients in Shanghai, in order to improve early diagnosis, precise subtyping, disease monitoring, and to provide a resource for translational research and novel therapy development. The main questions it aims to answer are: * Can multimodal data (clinical, imaging, electrophysiology, biospecimens, and genetics) help identify early biomarkers for PD and MSA? * Can precise subtyping and long-term monitoring predict disease progression and therapeutic response? Researchers will compare 600 PD patients and 100 MSA patients to evaluate differences in clinical features, biomarkers, imaging, and prognosis. Participants will: * Provide informed consent and complete baseline demographic and medical history collection. * Undergo standardized clinical evaluations, including motor and non-motor symptom scales, cognitive and quality-of-life assessments. * Provide biological samples (blood, saliva, optional CSF). * Receive brain imaging (MRI, optional PET/SPECT) and electrophysiological recordings (EEG, fNIRS). * Participate in longitudinal follow-up visits every 6 months for repeat assessments. This study will create a sustainable, multicenter, and sharable cohort platform to support early identification, personalized intervention, and therapeutic development for neurodegenerative diseases