Patient 1. Patient 1 was a 67-year-old woman. When she was 62, right-sided blindness developed over 4 days, but the vision was restored in a year. At age 65, she became quadriplegic and felt numb below the neck. After 3 months of rehabilitation, she could walk using a cane. At age 67, she developed bilateral blurred vision, paraplegia, and dysuria subacutely, …

Objectives: This placebo‐controlled, randomized study evaluated the efficacy and safety of opicapone 25‐mg and 50‐mg tablets in Japanese levodopa‐treated patients with Parkinson's disease and motor fluctuations.Methods: Japanese adults (n = 437, age 39–83 years) with Parkinson's disease (United Kingdom Parkinson's Disease Society criteria) received opicapone 25‐mg (n = 145), opicapone 50‐mg (n = 145), or placebo (n = 147) tablets over the double‐blind treatment period (14–15 weeks). The primary efficacy assessment was change in OFF‐time; secondary efficacy assessments included OFF/ON‐time responders (≥1 hour change from baseline), total ON‐time, ON‐time with and without troublesome dyskinesia, and Unified Parkinson's Disease Rating Scale.Results: The least squares mean (standard error) change in OFF‐time from baseline to the last visit was −0.42 (0.21) hour for the placebo group, −1.16 (0.22) hour for the opicapone 25 mg group, and −1.04 (0.21) hour for the opicapone 50 mg group. The percentage of ON‐time responders, changes in total ON‐time/ON‐time without troublesome dyskinesia, and Unified Parkinson's Disease Rating Scale II (at OFF) all showed statistically significant improvements versus placebo for both opicapone tablet doses (P < 0.05). Unified Parkinson's Disease Rating Scale III (at ON) was improved versus placebo in patients who received opicapone 50 mg (P < 0.05). Adverse events were more common in patients treated with opicapone 25 mg (60.0%) or opicapone 50 mg (54.5%) versus placebo (48.3%). The most commonly reported adverse event was dyskinesia (placebo, 2.7%; opicapone 25 mg, 9.0%; opicapone 50 mg, 12.4%).Conclusions: In Japanese patients, both opicapone 25 and 50 mg were significantly more effective than placebo with no dose‐dependent difference in efficacy, and both doses were well tolerated. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: In recent years, there has been increasing evidence that several lipid metabolism abnormalities play an important role in the pathogenesis of neurodegenerative diseases. However, it is still unclear which lipid metabolism abnormalities play the most important role in neurodegenerative diseases. Plasma lipid metabolomics (lipidomics) has been shown to be an unbiased method that can be used to explore lipid metabolism abnormalities in neurodegenerative diseases. Plasma lipidomics in neurodegenerative diseases has been performed only in idiopathic Parkinson’s disease (IPD) and Alzheimer’s disease (AD), and comprehensive studies are needed to clarify the pathogenesis. Methods: In this study, we investigated plasma lipids using lipidomics in individuals with neurodegenerative diseases and healthy controls (CNs). Plasma lipidomics was evaluated by liquid chromatography-tandem mass spectrometry (LC–MS/MS) in those with IPD, dementia with Lewy bodies (DLB), multiple system atrophy (MSA), AD, and progressive supranuclear palsy (PSP) and CNs. Results: The results showed that (1) plasma sphingosine-1-phosphate (S1P) was significantly lower in all neurodegenerative disease groups (IPD, DLB, MSA, AD, and PSP) than in the CN group. (2) Plasma monohexylceramide (MonCer) and lactosylceramide (LacCer) were significantly higher in all neurodegenerative disease groups (IPD, DLB, MSA, AD, and PSP) than in the CN group. (3) Plasma MonCer levels were significantly positively correlated with plasma LacCer levels in all enrolled groups. Conclusion: S1P, Glucosylceramide (GlcCer), the main component of MonCer, and LacCer are sphingolipids that are biosynthesized from ceramide. Recent studies have suggested that elevated GlcCer and decreased S1P levels in neurons are related to neuronal cell death and that elevated LacCer levels induce neurodegeneration by neuroinflammation. In the present study, we found decreased plasma S1P levels and elevated plasma MonCer and LacCer levels in those with neurodegenerative diseases, which is a new finding indicating the importance of abnormal sphingolipid metabolism in neurodegeneration.

We studied the processing of amyloid β-peptides (Aβs) including Aβ1-40, Aβ1-42 and pAβ3-42 by rat neutral cysteine protease bleomycin hydrolase (BH) according to the methods of SDS-PAGE, HPLC and matrix-assisted laser desorption/inonization time-of-flight mass spectrometry (MALDI-TOF MS). BH significantly processed them by novel features of its diverse activities. It initially cleaved at two sites, His14-Gln15 and Phe19-Phe20 bonds, in Aβ1-40 and Aβ1-42 by endopeptidase activity. The resultant peptides were degraded to short intermediates then to amino acids by aminopeptidase and/or carboxypeptidase activities. Also, full-length Aβs were clipped at the carboxyl(C)-terminal region. On the other hand, BH cleaved at only the His14-Gln15 bond in pβA3-42 within A short period of the reaction by endopeptidase activity, and processed the intermediates in order by carboxypeptidase activity. On processing by BH, it found that both fibrillar Aβ1-40 and Aβ1-42 were more resistant than non-fibrillar peptides. These results indicate that the processing specificity of BH depends upon the structure and sequence of Aβs.