Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial

It is believed that glycogen synthase kinase‐3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase‐3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double‐blind, placebo‐controlled trial in patients with mild‐to‐moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52‐week MRI. Automated, observer‐independent, atlas‐based, and mask‐based volumetry was done on high‐resolution, T1‐weighted, three‐dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: ?1.3% ± 1.4% vs. ?3.1% ± 2.3%, respectively), cerebrum (?1.3% ± 1.5% vs. ?3.2% ± 2.1%, respectively), parietal lobe (?1.6% ± 1.9% vs. ?4.1% ± 3.0%, respectively), and occipital lobe (?0.3% ± 1.8% vs. ?2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society     

Gut feelings about smoking and coffee in Parkinson's disease

Strong epidemiologic evidence suggests that smokers and coffee drinkers have a lower risk of Parkinson's disease (PD). The explanation for this finding is still unknown, and the discussion has focused on two main hypotheses. The first suggests that PD patients have premorbid personality traits associated with dislike for coffee‐drinking and smoking. The second posits that caffeine and nicotine are neuroprotective. We propose an alternative third hypothesis, in which both cigarette and coffee consumption change the composition of the microbiota in the gut in a way that mitigates intestinal inflammation. This, in turn, would lead to less misfolding of the protein alpha‐synuclein in enteric nerves, reducing the risk of PD by minimizing propagation of the protein aggregates to the central nervous system, where they otherwise can induce neurodegeneration. © 2014 International Parkinson and Movement Disorder Society