Present and future of disease-modifying therapies in multiple system atrophy

Lopez-Cuina, Miguel; Foubert‐Samier, Alexandra; Tison, François; Meissner, Wassilios G.

doi:10.1016/j.autneu.2017.12.008

Cited by 6 publications

(10 citation statements)

References 98 publications

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“…Therefore, disease-modifying therapies remain an urgent unmet need. 2,3 The neuropathological hallmark is the accumulation of α-synuclein in oligodendrocytes, forming glial cytoplasmic inclusions, [4][5][6] qualifying MSA as a synucleinopathy together with Parkinson's disease and Lewy body dementia. The origin of α-synuclein in glial cytoplasmic inclusions remains under debate, and the exact mechanisms underlying the pathogenesis are only incompletely understood.…”

Section: Treatmentmentioning

confidence: 99%

A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy

Meissner¹,

Traon

Foubert‐Samier

et al. 2020

Movement Disorders

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Section: Treatmentmentioning

confidence: 99%

A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy

Meissner¹,

Traon

Foubert‐Samier

et al. 2020

Movement Disorders

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“…Multiple system atrophy is an uncommon neurodegenerative disease that is pathologically characterized by a combination of parkinsonism, cerebellar ataxia, and autonomic dysfunction (Lopez-Cuina et al, 2018;Monzio Compagnoni and Di Fonzo, 2019). MSA is divided into two subtypes, MSA with parkinsonism features (MSA-P), which exhibits bradykinesia, rigidity, postural instability, and tremor, or MSA with cerebellar features (MSA-C), which exhibits gait ataxia, ataxic dysarthria, limb ataxia, and sustained gaze-evoked nystagmus (Gilman et al, 1999).…”

Section: Msa (Multiple System Atrophy)mentioning

confidence: 99%

The Role of Glial Mitochondria in α-Synuclein Toxicity

Jeon

Kwon

et al. 2020

Front. Cell Dev. Biol.

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The abnormal accumulation of alpha-synuclein (α-syn) aggregates in neurons and glial cells is widely known to be associated with many neurodegenerative diseases, including Parkinson’s disease (PD), Dementia with Lewy bodies (DLB), and Multiple system atrophy (MSA). Mitochondrial dysfunction in neurons and glia is known as a key feature of α-syn toxicity. Studies aimed at understanding α-syn-induced toxicity and its role in neurodegenerative diseases have primarily focused on neurons. However, a growing body of evidence demonstrates that glial cells such as microglia and astrocytes have been implicated in the initial pathogenesis and the progression of α-Synucleinopathy. Glial cells are important for supporting neuronal survival, synaptic functions, and local immunity. Furthermore, recent studies highlight the role of mitochondrial metabolism in the normal function of glial cells. In this work, we review the complex relationship between glial mitochondria and α-syn-mediated neurodegeneration, which may provide novel insights into the roles of glial cells in α-syn-associated neurodegenerative diseases.

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“…Neuroprotection is an urgent unmet treatment need, with hopes for the future including novel targets and methodological improvements. 2 Preclinical pipeline for neuroprotection in MSA Following the progress in our understanding of the underlying disease mechanisms, α-synuclein is currently the main target for the development of possible neuroprotective treatments. For illustration, the European ARTEMIS consortium is currently testing the efficacy of 4 complementary strategies targeting α-synuclein in preclinical models of MSA (Fig.…”

Section: Treatmentmentioning

confidence: 99%

“…Some symptomatic treatments are available, whereas neuroprotection remains an unmet urgent treatment need. 2,3 In this review, we critically appraise significant developments of the past decade, discuss unsolved questions, and highlight some perspectives. We first focus on the origin and role of α-synuclein in the pathogenesis of MSA.…”

mentioning

confidence: 99%

Multiple System Atrophy: Recent Developments and Future Perspectives

et al. 2019

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Multiple system atrophy (MSA) is a rare and fatal neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar impairment, and autonomic dysfunction. The pathologic hallmark is the accumulation of aggregated α‐synuclein in oligodendrocytes, forming glial cytoplasmic inclusions, which qualifies MSA as a synucleinopathy together with Parkinson's disease and dementia with Lewy bodies. The underlying pathogenesis is still not well understood. Some symptomatic treatments are available, whereas neuroprotection remains an urgent unmet treatment need. In this review, we critically appraise significant developments of the past decade with emphasis on pathogenesis, diagnosis, prognosis, and treatment development. We further discuss unsolved questions and highlight some perspectives. © 2019 International Parkinson and Movement Disorder Society

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Present and future of disease-modifying therapies in multiple system atrophy

Cited by 6 publications

References 98 publications

A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy

A Phase 1 Randomized Trial of Specific Active α‐Synuclein Immunotherapies PD01A and PD03A in Multiple System Atrophy

The Role of Glial Mitochondria in α-Synuclein Toxicity

Multiple System Atrophy: Recent Developments and Future Perspectives

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