Enzyme replacement therapy is currently the only approved treatment for Pompe disease, due to acid α-glucosidase deficiency. Clinical efficacy of this approach is variable, and more effective therapies are needed. We showed in preclinical studies that chaperones stabilize the recombinant enzyme used for enzyme replacement therapy. Here, we evaluated the effects of a combination of enzyme therapy and a chaperone on α-glucosidase activity in Pompe disease patients. α-Glucosidase activity was analyzed by tandem-mass spectrometry in dried blood spots from patients treated with enzyme replacement therapy, either alone or in combination with the chaperone N-butyldeoxynojirimycin given at the time of the enzyme infusion. Thirteen patients with different presentations (3 infantile-onset, 10 late-onset) were enrolled. In 11 patients, the combination treatment resulted in α-glucosidase activities greater than 1.85-fold the activities with enzyme replacement therapy alone. In the whole patient population, α-glucosidase activity was significantly increased at 12 hours (2.19-fold, P = 0.002), 24 hours (6.07-fold, P = 0.001), and 36 hours (3.95-fold, P = 0.003). The areas under the curve were also significantly increased (6.78-fold, P = 0.002). These results suggest improved stability of recombinant α-glucosidase in blood in the presence of the chaperone.

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Post-marketing surveillance studies are needed to assess the long-term safety, compliance and clinical efficacy of interferon beta-1a (IFNbeta-1a) therapy in multiple sclerosis (MS) patients. The goals of this study were to (i) assess the safety, compliance and clinical efficacy of long-term intramuscular (i.m.) IFNbeta-1a therapy in a large cohort of patients, and (ii) suggest possible predictors of therapeutic response. A total of 255 patients were included in the study. Mean time on therapy was 31.7 +/- 19.3 months. Within 3 years, 31% of patients discontinued treatment, mainly for disease activity. No significant sustained blood analysis alteration was observed over time, apart from a decrease of cholesterol levels. After 3 years of treatment, mean Expanded Disability Status Scale (EDSS) scores increased by 0.4 points compared with baseline. The mean annual relapse rate was reduced compared with baseline. Patients with < or = 2 relapses in the previous 2 years and with baseline EDSS scores of < or = 2 had a longer estimated time to first relapse and to progression and first relapse, respectively. These results confirm the safety and suggest a sustained effectiveness of i.m. IFNbeta-1a, extending the reported follow-up period to 6.3 years, and hypothesize the presence of possible predictors of clinical outcome.

Objectives The enforcement of complete lockdown with home confinement has been necessary to limit SARS-CoV-2 contagions in Italy, one the most affected countries worldwide. Simultaneously, in several Emergency Departments, a reduction in cardio- and cerebrovascular presentations was noticed. This study analyses the impact of Covid-19 pandemic and lockdown measures on the incidence of stroke, in Campania, the most densely-populated region in Italy. Materials and Methods We retrospectively analyzed data regarding acute stroke patients presenting at 5 Campania stroke hubs, before and after the issue of lockdown in Italy on March 9th, 2020. Results Compared to the pre-lockdown, we observed a significant reduction in the number of acute reperfusion treatments in stroke (P for interact 0.001); however the global number of patients presenting with acute stroke did not significantly differ. The time to reach medical attention was significantly longer in the lockdown phase (230 versus 154 min, P 0.016). For patients who underwent acute reperfusion treatment we also observed significantly longer time-to-imaging (30 versus 40 min, P 0.0005) and a trend to longer time-to-needle (75 versus 90 min P 0.23), but not time-to-groin. Conclusions This study showed the reduction in acute reperfusion treatments for acute ischemic stroke and the slowdown of stroke pathways, during the lockdown phase of Covid-19 pandemic, in Campania, the third-most-populous and the most-densely populated Italian Region. In the next future, the risk for high-grade disability and death, due to delayed or even avoided hospital presentation due to fear of contagion, may be high.

AimDysphagia is a known complication in Pompe Disease (PD), a severe metabolic myopathy due to alpha-glucosidase deficiency. Enzyme replacement therapy (ERT) with alglucosidase alfa is the only approved therapy for PD. Presently no data are available on the effects of ERT on dysphagia in PD patients. The aim of this work is to evaluate the course of this complication in a 6 years old boy affected by PD after treatment with ERT.MethodsDysphagia was assessed by Videofluoroscopic Swallowing Study (VFSS) at baseline, before the start of ERT and after 36 months of therapy. We used the Dysphagia Severity Rating Scale (DSS) to define the severity grade of dysphagia.ResultsVFSS performed at baseline revealed complete incoordination of oral stage swallowing which was classified as a grade 1 dysphagia according to DSS. After 36 months of treatment VFSS revealed normal swallowing, classified as grade 0 by DSS.ConclusionOur results suggest that ERT is effective in improving dysphagia. VFSS may be a useful tool to investigate and monitor swallowing disorders in patients affected by PD.