The authors propose that axonal damage markers in CSF may discriminate between subtypes of ALS and that they could be used as markers for therapeutic trials. CSF NfH was superior to tau in these discriminations.

Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment. Using the two-dimensional difference gel electrophoresis (2-D-DIGE) technology for comparative analysis, we compared CSF samples from patients with MS of the relapse-remitting type (RRMS, n = 12) and from patients with clinically isolated syndrome (CIS, n = 12) suggestive of a first demyelinating attack with neurologically normal controls. Protein spots that showed more than two-fold difference between patients and controls were selected for further analysis with MALDI-TOF mass spectrometry. Immunoblot analysis was performed to confirm the validity of individual candidate proteins. In RRMS, we identified 1 up-regulated and 10 down-regulated proteins. In CIS, 2 up-regulated and 11 down-regulated proteins were identified. One of these proteins (Apolipoprotein A1) was confirmed by immunoblot. Though the pathophysiological role of these proteins still remains to be elucidated in detail and further validation is needed, these findings may have a relevant impact on the identification of disease-specific markers.

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BackgroundSiena Biotech SpA is developing selisistat (SEN0014196) as a potentially disease-modifying therapy for HD. Selsistat is a potent and selective SirT1 inhibitor (IC50 98 nM) that has shown benefit across a range of preclinical models for HD, from cells and neurons transfected with mutant huntingtin to transgenic Drosophila and R6/2 mice. The compound has shown to be safe and well tolerated in healthy volunteers and has a favourable pharmacokinetic profile.AimThe current study was designed to provide biophase samples for analysis of a series of potential target engagement and disease-modification read-outs, helping to establish a proof-of-principle and aid in dose selection for future safety and efficacy studies.MethodsA total of 63 HD patients with a wide range of CAG repeats and disease burden scores were screened across six sites in Germany (Bochum, Ulm), Poland (Krakow, Warsaw) and the UK (London, Manchester). Patients were randomised to receive either 10 or 100 mg of selisistat or placebo for 2 weeks. Safety data collected included vital signs, ECGs, clinical laboratory parameters and type and frequency of adverse events. Clinical assessments included UHDRS and a cognitive battery. Serial blood sampling for pharmacokinetics and pharmacodynamics was performed on days 1 and 14 and at follow-up after a washout phase of 14 days.Results and ConclusionsA total of 55 patients completed the treatment as per protocol; there were four screening failures and four patients withdrew consent. No Serious Adverse Events were reported and no patient withdrew from the study as a result of an adverse event. We will present full data on safety, tolerability, pharmacokinetics and clinical assessments, while pharmacodynamic data will be reported elsewhere.

Purpose Instrumental assessments to visualize the structure and functions of the different stages of swallowing and to identify the risk of aspiration include Videofluoroscopic evaluation (VFSS) and Fiberoptic Endoscopic Evaluation of Swallowing (FEES). However, there are only a few studies on dysphagia in Huntington‘s Disease (HD). Recently, a guideline paper was published by the EHDN Standards of Care Speech and Language Therapy Working Group (Hamilton, Heemskerk et al. 2012), but there is no report on the evaluation of dysphagia by FEES so far. Therefore, the aim of the study was to determine the dysphagic symptoms spilling, residuals, penetration and aspiration of puree, liquids and solid food by FEES according to HD-stage. Furthermore, this study is a pilot project to establish predictors for dysphagia in clinical assessment in HD. Method This study investigated 29 HD patients with the Clinical Swallowing Assessment NOD-Stepwise Concept by GUT-Team 2009 (NOD) (Ickenstein, Hofmayer et al. 2009) followed by Fiberendoscopic Evaluation of Swallowing (FEES) (Langmore 2006) and compared morphological with functional data to determine the dysphagic symptoms spilling, residuals, penetration and aspiration in the different HD-Stages as well as predictors in clinical swallowing assessment for dysphagia (Daniels, McAdam et al. 1997) in HD. The consistencies used in FEES have been puree, water, thickened liquid, bread, apple and pill. Results There were no statistical significance in spilling between HD-stages. Residuals of puree, penetration and aspiration as well as PEG-Recommendation showed significant differences between HD-stages. Conclusions FEES allows clinicians not only to characterise dysphagia precisely but also to find out an appropriate compensatory method and verifies its effectiveness by correlating morphological with functional data in HD-Patients. There is a higher risk for penetration and aspiration in later stages of HD inducing recommendation for Percutaneous Endoscopic Gastrostomy (PEG). Dysarthria, dysphonia and abnormal gag reflex show a high sensitivity to predict dysphagia. Dysarthria, dysphonia, gag refelx and voluntary cough distinguished Dysphagia in sence of a worst PAS-Score of all tested consistencies in FEES higher than 2 (p < 0.05). The 90 ml water test is not a sufficient diagnostic instrument to exclude dysphagia in HD. Due to lack of specificity of dysphagia, it is useful to initiate an imaging diagnosis of dysphagia. This study is a pilot project and further studies with larger groups of HD patients must be performed.

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