NON-PHARMACEUTICAL TREATMENT PIPELINE

** Previous clinical biomarker work funded by the MSA Coalition **

Grant: “Inside the gait – a new era on the horizon for atypical parkinsonian disorders”
Awardee: Gregor Wenning, MD, PhD
MSA Coalition Grant #2016-09-008 – $50,000

Mobility in Atypical Parkinsonism: a Trial of Physiotherapy (Mobility_APP)

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04608604

Patients with atypical parkinsonism often show gait and mobility impairment manifesting in early disease stages.

In order to maintain mobility and physical autonomy as long as possible for these patients, we will examine the effect of two types of physiotherapy in patients with multiple system atrophy (MSA), progressive supranuclear gaze palsy (PSP) and idiopathic Parkinson’s disease (IPD).

The study is divided into an ambulant daily in-patient physiotherapy phase, followed by a home-based training phase. At the beginning and the end of the study, the patients daily activity will be recorded for one week using Physical Activity Monitoring (PAM) sensors.

The aim of this double-blind, randomized-controlled study is to determine effective physiotherapy in patients with atypical parkinsonian syndromes in order to maintain mobility for as long as possible.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

Comprehensive Swallowing Rehabilitation in Patients With MSA

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04782284

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease characterized by parkinsonism, cerebellar syndrome, and autonomic failure. Dysphagia is a clinically significant symptom leading to pneumonia that causes death in patients with MSA. Although the symptoms of dysphagia in the two subtypes of MSA-the parkinsonian variant and the cerebellar variant- are different, there is no significant difference in the latency to onset of tube feeding. Therefore, effective intervention is needed to improve the safety and efficiency of swallowing regardless of the subtypes of MSA.

Although swallowing rehabilitation has been widely applied for swallowing disorders in patients with MSA, few studies have reported the clinical effect of applying swallowing therapy. Comprehensive swallowing rehabilitation has focused on functional muscle training, compensatory swallowing maneuvers, and thermal-tactile stimulation, which is used to treat dysphagia from stroke, Parkinson’s disease, and head and neck cancer. Therefore, this study aims to investigate the effect of comprehensive swallowing rehabilitation in patients with MSA.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

** This Clinical Study is partially funded by the MSA Coalition **

Grant: “Abdominal Binders to treat Orthostatic Hypotension in Multiple System Atrophy”
Awardees: Gregor Wenning, MD, PhD & Alessandra Fanciulli MD, PhD & Cecilia Raccagni MD
MSA Coalition Grant #2020-05-002 – $50,000

Abdominal Binders to Treat Orthostatic Hypotension in Parkinsonian Syndromes (ABOH-PS)

The purpose of the present clinical trial is to determine whether the use of an elastic abdominal binder is effective in the non-pharmacological management of symptomatic, neurogenic orthostatic hypotension (OH) in individuals suffering from Parkinson’s disease (PD) or Parkinson variant multiple system atrophy (MSA-P).

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04920552

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

Optimizing BCI-FIT: Brain Computer Interface – Functional Implementation Toolkit (BCI-FIT)

For study details See: https://clinicaltrials.gov/ct2/show/NCT04468919

This project adds to non-invasive BCIs for communication for adults with severe speech and physical impairments due to neurodegenerative diseases. Researchers will optimize & adapt BCI signal acquisition, signal processing, natural language processing, & clinical implementation. BCI-FIT relies on active inference and transfer learning to customize a completely adaptive intent estimation classifier to each user’s multi-modality signals simultaneously. 3 specific aims are: 1. develop & evaluate methods for on-line & robust adaptation of multi-modal signal models to infer user intent; 2. develop & evaluate methods for efficient user intent inference through active querying, and 3. integrate partner & environment-supported language interaction & letter/word supplementation as input modality. The same 4 dependent variables are measured in each SA: typing speed, typing accuracy, information transfer rate (ITR), & user experience (UX) feedback. Four alternating-treatments single case experimental research designs will test hypotheses about optimizing user performance and technology performance for each aim.Tasks include copy-spelling with BCI-FIT to explore the effects of multi-modal access method configurations (SA1.4a), adaptive signal modeling (SA1.4b), & active querying (SA2.2), and story retell to examine the effects of language model enhancements. Five people with SSPI will be recruited for each study. Healthy control participants will be recruited for experiments in SA2.2 and SA3.4. Study hypotheses are: (SA1.4a) A customized BCI-FIT configuration based on multi-modal input and personal metadata will improve typing accuracy on a copy-spelling task compared to a user’s existing AAC access method. (SA1.4b) Adaptive signal modeling will mitigate the effects of changes in user state on typing accuracy during a copy-spelling task with BCI-FIT. (SA2.2) Either of two methods of adaptive querying will improve BCI-FIT typing accuracy for users with mediocre AUC scores. (SA3.4) Language model enhancements, including a combination of partner and environmental input and word completion during typing, will improve typing performance with BCI-FIT, as measured by ITR during a story-retell task. Optimized recommendations for a multi-modal BCI for each end user will be established, based on an innovative combination of clinical expertise, user feedback, customized multi-modal sensor fusion, and reinforcement learning.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

** Previous biomarker work funded by the MSA Coalition **

Grant: “Biomarker Development in MSA”
Awardee: Roy Freeman, MD
MSA Coalition Grant #2013-12-005 – $25,000

Synuclein-One Study

stem Atrophy (IRAMS)

Misfolded Proteins in the Skin of People With Parkinson’s Disease and Other Parkinsonism

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04518059

The purpose of this study is to determine whether identification of misfolded proteins in the skin will help to determine what sort of parkinsonism someone has. We seek to demonstrate whether someone has a synucleinopathy such as Parkinson’s disease (PD), multiple system atrophy (MSA), or dementia with Lewy bodies(DLB), as opposed to a tauopathy such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) or no parkinsonism at all (control).

This is a clinical research study for patients with parkinsonism, including Parkinson’s disease, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies. Parkinsonism can be difficult to diagnose, especially in the early stages of the disease. Skin punch biopsy could be a useful and way to diagnose and measure the severity of these conditions. Given that there currently is no proven way to determine that someone has a synucleinopathy such as PD and not a tauopathy, this is a novel study that may lead to better ways to diagnose people with parkinsonism. The purpose of the study is to identify changes on a skin punch biopsy, in which small samples of skin are removed and sent to the laboratory for examination. We are seeking to measure the amount of misfolded alpha-synuclein in someone’s skin. Participation will last between 1 and 2 years and will involve between 2 and 4 visits. Visits will include a physical examination, questionnaires, a memory test, blood draws, and a single visit for skin punch biopsies. We will also be looking to enroll volunteers to serve as “controls,” who do not have any neurological illness.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

** Previous biomarker work funded by the MSA Coalition **

Grant: “Plasma exosomal IRS-1pS312 as biomarker for MSA”
Awardee: Wassilios Meissner, MD, PhD
MSA Coalition Grant #2017-10-005 – $50,000

Insulin Resistance in Multiple System Atrophy (IRAMS)

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04250493

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder. The pathologic hallmark is the accumulation of aggregated alpha-synuclein in oligodendrocytes forming glial cytoplasmic inclusions. Some symptomatic treatments are available while disease-modification remains an unmet treatment need. Post-mortem findings suggest insulin resistance, i.e. reduced insulin signaling, in the brains of MSA patients.

The aim of this study is to further characterize peripheral and central insulin resistance in MSA patients, thereby validating this target for future treatment trials. For this purpose, fasting blood glucose and insulin levels will be determined in samples of MSA patients and healthy controls for a homeostatic model assessment of insulin resistance (HOMA). Additionally, IRS-1pS312 will be measured in neural-derived plasma exosomes of MSA patients and healthy controls.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

A Pilot Biomarker Study Assessing Alpha-synuclein Aggregates Across Biofluid Reservoirs in Patients With Synucleinopathies

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04020198

This will be an observational study looking at clinical and biomarker characteristics in patients with Parkinson’s Disease (PD), Multiple System Atrophy (MSA), Rapid Eye Movement Sleep Behavior Disorder (RBD), Normal Pressure Hydrocephalus and matched controls. Saliva, plasma, serum, urine, and cerebrospinal fluid (CSF) samples will be collected from participants.

Misfolded alpha-synuclein aggregates have the potential to serve as an early biomarker for PD and MSA, increasing the ability to diagnose and treat individuals with these diseases earlier. This study examines the effectiveness of using a novel technique for distinguishing between different parkinsonian disorders by measuring small misfolded α-synuclein aggregates in different biofluids.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

TMS Treatment in Multiple System Atrophy With Fatigue (TMSMSAF)

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04313530

Transcranial magnetic stimulation (TMS) is a procedure that has been shown to improve fatigue in chronic sufferers. It uses a plastic covered coil that sends a magnetic pulse through the skull into the brain and by targeting particular areas in the brain it can be used to help modulate the perception of fatigue.

The study intends to use this technique to treat such a disabling symptom in patients who suffer from Multiple System Atrophy (MSA). Initially the aim is to study this technique in 22 MSA patients who are suffering from fatigue . These patients would require an resting-state funtional MRI before and after the stimulation. The stimulation would be performed ten sessions and the patients would be assessed by a clinician using well recognized clinical tools.

It is anticipated that there will be a meaningful improvement in fatigue. It is also anticipated that TMS is a safety technique to use in MSA patients . Our findings will revealed that fatigue may be associated with an altered default mode network and sensorimotor network connectivity in MSA patients. We hypothesize that these divergent motor and cognitive networks connectivity changes and their adaptive or maladaptive functional outcome may play a prominent role in the pathophysiology of fatigue in MSA.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

Deep Brain Stimulation for Autonomic and Gait Symptoms in Multiple System Atrophy (STAG-MSA)

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT03593512

Patients referred to neurosurgery routinely and safely undergo deep brain stimulation (DBS) for treatment of symptoms related to neurodegenerative conditions, most commonly Parkinson’s disease.

In the investigators experience, and published evidence shows, that stimulation has effects on the autonomic nervous system. In patients undergoing therapeutic DBS for a particular subtype of Parkinsonism, Multiple System Atrophy, the further effects on autonomic parameters such as blood pressure and bladder symptoms as well as the originally intended indications (gait and movement disorder) will be investigated. The mechanisms of any effects will also be studied by using a number of techniques such as magnetoencephalography (MEG) and Muscle Sympathetic Nerve Activity (MSNA) recording.

Key goals are to:

1. Demonstrate that stimulation of the peduculopontine nucleus (PPN) improves autonomic function and has an attendant improvement on patients’ quality of life
2. Investigate the role of the PPN and how it interacts with other brain areas.

This translational strategy will lead to a larger efficacy study of DBS for MSA as well as revolutionizing neural-based treatments in other autonomic disorders such as orthostatic hypotension and pure autonomic failure.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

** Previous clinical work partially funded by the MSA Coalition **

Grant: “Global MSA Registry (Glomsar) Case Fees”
Awardee: Lucy Norcliffe-Kaufmann, PhD
MSA Coalition Grant #MSAC 2018-12-001 – $38,600

*** VIDEO: What is a Natural History Study https://vimeo.com/465621605#t=21m30s

Natural History Study of Synucleinopathies

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT01799915

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.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

*** Video: Announcing Track-MSA Study https://vimeo.com/465621605#t=29m21s

TRACK-MSA: A Longitudinal Study to Define Outcome Measures in Multiple System Atrophy

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04450992

TRACK-MSA is an observational, non-interventional, longitudinal natural history study to define changes in clinical, neurological, blood, CSF, and neuroimaging biomarkers in patients with multiple system atrophy (MSA) comparing baseline to 6-month and 1-year assessments. The study will enroll 50 patients with MSA-P or MSA-C at 2 or more participating sites.

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.

*** VIDEO: What is a Natural History Study https://vimeo.com/465621605#t=21m30s

Natural History and Disease Progression Biomarkers of Multiple System Atrophy (ASPIRE-MSA)

For study information see: https://www.clinicaltrials.gov/ct2/show/NCT04229173

Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disease characterised by a variable combination of parkinsonism, cerebellar impairment and autonomic dysfunction. The neuropathological hallmark is the accumulation of alpha-synuclein in oligodendrocytes. While some symptomatic treatments exist, neuroprotective treatments for MSA remain an urgent, unmet need. Moreover, at present there is not a single surrogate biomarker of MSA which could be used to inform clinical trials.

This study seeks to characterise the natural history of MSA on a panel of candidate biomarkers, pre-selected for being putative surrogates of the underlying neurodegenerative process

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NOTE: All of the above information is intended to assist MSA patients and their families in having a conversation with doctors, none of it should be considered medical advice or endorsements of any particular drugs or therapies. Always consult a licensed medical practitioner for expert care.