Lancet neurology
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Randomized Controlled Trial Multicenter Study
Pramipexole in patients with early Parkinson's disease (PROUD): a randomised delayed-start trial.
In models of dopaminergic neuronal loss, the dopamine agonist pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). ⋯ Boehringer Ingelheim GmbH.
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Randomized Controlled Trial
Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study.
Siponimod is an oral selective modulator of sphingosine 1-phosphate receptor types 1 and type 5, with an elimination half-life leading to washout in 7 days. We aimed to determine the dose-response relation of siponimod in terms of its effects on brain MRI lesion activity and characterise safety and tolerability in patients with relapsing-remitting multiple sclerosis. ⋯ Novartis Pharma AG.
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Fragile X syndrome, the most common heritable form of cognitive impairment, is caused by epigenetic silencing of the fragile X (FMR1) gene owing to large expansions (>200 repeats) of a non-coding CGG-repeat element. Smaller, so-called premutation expansions (55-200 repeats) can cause a family of neurodevelopmental phenotypes (attention deficit hyperactivity disorder, autism spectrum disorder, seizure disorder) and neurodegenerative (fragile X-associated tremor/ataxia syndrome [FXTAS]) phenotypes through an entirely distinct molecular mechanism involving increased FMR1 mRNA production and toxicity. Results of basic cellular, animal, and human studies have helped to elucidate the underlying RNA toxicity mechanism, while clinical research is providing a more nuanced picture of the range of clinical manifestations. Advances of knowledge on both mechanistic and clinical fronts are driving new approaches to targeted treatment, but two important necessities are emerging: to define the extent to which the mechanisms contributing to FXTAS also contribute to other neurodegenerative and medical disorders, and to redefine FXTAS in view of its differing presentations and associated features.
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Parkinson's disease is a common progressive neurodegenerative disease, of which the main neuropathological hallmark is dopaminergic neuronal loss. Increased attention has been directed towards non-motor symptoms in Parkinson's disease, such as cognitive impairment and behavioural disorders. Clinical and experimental findings support the view that the hippocampus, a temporal lobe structure involved in physiological learning and memory, is also implicated in the cognitive dysfunction seen in some patients with Parkinson's disease. ⋯ This structure is also implicated in the pathophysiology of other non-motor symptoms, such as impulse control disorders, anosmia, and fatigue. Evidence from clinical observations and experimental studies suggest a complex hippocampal cross-talk among the dopaminergic and other transmitter systems. Furthermore, neurotrophic factors might interact with the hippocampal dopaminergic system having possible implications on the non-motor symptoms seen in patients with Parkinson's disease.