Therapeutic advances in multiple system atrophy and progressive supranuclear palsy

@article{Poewe2015TherapeuticAI,
  title={Therapeutic advances in multiple system atrophy and progressive supranuclear palsy},
  author={Werner Poewe and Philipp Mahlknecht and Florian Krismer},
  journal={Movement Disorders},
  year={2015},
  volume={30}
}
Multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) are relentlessly progressive neurodegenerative diseases leading to severe disability and ultimately death within less than 10 y. Despite increasing efforts in basic and clinical research, effective therapies for these atypical parkinsonian disorders are lacking. Although earlier small clinical studies in MSA and PSP mainly focused on symptomatic treatment, advances in the understanding of the molecular underpinnings of these… 
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References

SHOWING 1-10 OF 63 REFERENCES
Rational therapeutic approaches to progressive supranuclear palsy.
TLDR
The current pathophysiological concepts driving these exciting therapeutic developments are presented and several hypothesis-driven therapeutic approaches aiming at disease-modification rather than mere symptomatic neurotransmitter-replacement therapy are presented.
Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges
TLDR
The emerging nosology in this field is reviewed and it is emphasised that the pathological events and processes that lead to the accumulation of phosphorylated tau protein in the brain are best considered as dynamic processes that can develop at different rates, leading to different clinical phenomena.
Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial
TLDR
In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes, and a trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem.
Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: The NNIPPS Study
TLDR
Riluzole did not have a significant effect on survival or rate of functional deterioration in PSP or MSA, although the study reached over 80% power to detect the hypothesized drug effect within strata, and the NNIPPS diagnostic criteria were consistent and valid.
Clinical trials: past, current, and future for atypical Parkinsonian syndromes.
TLDR
Randomized, placebo-controlled clinical trials of atypical parkinsonian disorders such as progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, or multiple system atrophy are reviewed.
Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2/3 trial
TLDR
Davunetide is not an effective treatment for PSP and clinical trials of disease-modifying treatment are feasible in patients with PSP and should be pursued with other promising tau-directed treatments.
Autologous mesenchymal stem cell therapy for progressive supranuclear palsy: translation into a phase I controlled, randomized clinical study
TLDR
This is the first clinical trial to be applied in a no-option parkinsonism that aims to test the safety and to exploit the properties of autologous mesenchymal stem cells in reducing disease progression and to preliminarily explore its efficacy by excluding the placebo effect.
Short‐term effects of coenzyme Q10 in progressive supranuclear palsy: A randomized, placebo‐controlled trial
TLDR
Clinically, the PSP rating scale and the Frontal Assessment Battery improved slightly, but significantly, upon CoQ10 treatment compared to placebo, and long‐term treatment might have a disease‐modifying, neuroprotective effect.
Efficacy of rasagiline in patients with the parkinsonian variant of multiple system atrophy: a randomised, placebo-controlled trial
TLDR
Treatment with rasagiline 1 mg per day did not show a significant benefit as assessed by UMSARS, and the study confirms the sensitivity of clinical outcomes for multiple system atrophy to detect clinically significant decline, even in individuals with early disease.
Premotor signs and symptoms of multiple system atrophy
TLDR
Non-motor symptoms and signs of multiple system atrophy often precede the onset of classic motor manifestations, and this prodromal phase is estimated to last from several months to years.
...
1
2
3
4
5
...