Research activity and capability in the European reference network MetabERN

Background: MetabERN is one of the 24 European Reference Networks created according to the European Union directive 2011/24/EU on patient’s rights in cross border healthcare. MetabERN associates 69 centres in 18 countries, which provide care for patients with Hereditary Metabolic Diseases, and have the mission to reinforce research and provide training for health professionals in this field. MetabERN performed a survey in December 2017 with the aim to produce an overview documenting research activities and potentials within the network. As the centres are multidisciplinary, separated questionnaires were sent to the clinical, university and laboratory teams. Answers were received from 52 out of the 69 centres of the network, covering 16 countries. A descriptive analysis of the information collected is presented. Results: The answers indicate a marked interest of the respondents for research, who expressed high motivation and commitment, and estimated that the conditions to do research in their institution were mostly satisfactory. They are active in research, which according to several indicators, is competitive and satisfies standards of excellence, as well as the education programs offered in the respondent’s universities. Research in the centres is primarily performed in genetics, pathophysiology, and epidemiology, and focuses on issues related to diagnosis. Few respondents declared having activity in human and social sciences, including research on patient’s quality of life, patient’s awareness, or methods for social support. Infrastructures offering services for medical research were rarely known and used by respondents, including national and international biobanking platforms. In contrast, respondents often participate to patient registries, even beyond their specific field of interest. Conclusions: Taken as a whole, these results provide an encouraging picture of the research capacities and activities in the MetabERN network, which, with respect to the number and representativeness of the investigated centres, gives a comprehensive picture of research on Hereditary Metabolic Diseases in Europe, as well as the priorities for future actions. Marginal activity in human and social sciences points out the limited multidisciplinary constitution of the responding teams with possible consequences on their current capability to participate to patient’s empowerment programs and efficiently collaborate with patient’s advocacy groups

A generic emergency protocol for patients with inborn errors of metabolism causing fasting intolerance: A retrospective, single-center study and the generation of www.emergencyprotocol.net

Patients with inborn errors of metabolism causing fasting intolerance can experience acute metabolic decompensations. Long-term data on outcomes using emergency letters are lacking. This is a retrospective, observational, single-center study of the use of emergency letters based on a generic emergency protocol in patients with hepatic glycogen storage diseases (GSD) or fatty acid oxidation disorders (FAOD). Data on hospital admissions, initial laboratory results, and serious adverse events were collected. Subsequently, the website www.emergencyprotocol.net was generated in the context of the CONNECT MetabERN eHealth project following multiple meetings, protocol revisions, and translations. Representing 470 emergency protocol years, 127 hospital admissions were documented in 54/128 (42%) patients who made use of emergency letters generated based on the generic emergency protocol. Hypoglycemia (here defined as glucose concentration 5 years. Convulsions, coma, or death was not documented. By providing basic information, emergency letters for individual patients with hepatic GSD or the main FAOD can be generated at www.emergencyprotocol.net, in nine different languages. Generic emergency protocols are safe and easy for home management by the caregivers and the first hour in-hospital management to prevent metabolic emergencies in patients with hepatic GSD and medium-chain Acyl CoA dehydrogenase deficiency. The website www.emergencyprotocol.net is designed to support families and healthcare providers to generate personalized emergency letters for patients with hepatic GSD and the main FAOD

Research activity and capability in the European reference network MetabERN

BACKGROUND: MetabERN is one of the 24 European Reference Networks created according to the European Union directive 2011/24/EU on patient's rights in cross border healthcare. MetabERN associates 69 centres in 18 countries, which provide care for patients with Hereditary Metabolic Diseases, and have the mission to reinforce research and provide training for health professionals in this field. MetabERN performed a survey in December 2017 with the aim to produce an overview documenting research activities and potentials within the network. As the centres are multidisciplinary, separated questionnaires were sent to the clinical, university and laboratory teams. Answers were received from 52 out of the 69 centres of the network, covering 16 countries. A descriptive analysis of the information collected is presented. RESULTS: The answers indicate a marked interest of the respondents for research, who expressed high motivation and commitment, and estimated that the conditions to do research in their institution were mostly satisfactory. They are active in research, which according to several indicators, is competitive and satisfies standards of excellence, as well as the education programs offered in the respondent's universities. Research in the centres is primarily performed in genetics, pathophysiology, and epidemiology, and focuses on issues related to diagnosis. Few respondents declared having activity in human and social sciences, including research on patient's quality of life, patient's awareness, or methods for social support. Infrastructures offering services for medical research were rarely known and used by respondents, including national and international biobanking platforms. In contrast, respondents often participate to patient registries, even beyond their specific field of interest. CONCLUSIONS: Taken as a whole, these results provide an encouraging picture of the research capacities and activities in the MetabERN network, which, with respect to the number and representativeness of the investigated centres, gives a comprehensive picture of research on Hereditary Metabolic Diseases in Europe, as well as the priorities for future actions. Marginal activity in human and social sciences points out the limited multidisciplinary constitution of the responding teams with possible consequences on their current capability to participate to patient's empowerment programs and efficiently collaborate with patient's advocacy groups

Iminosugar-Based Inhibitors of Glucosylceramide Synthase Increase Brain Glycosphingolipids and Survival in a Mouse Model of Sandhoff Disease

The neuropathic glycosphingolipidoses are a subgroup of lysosomal storage disorders for which there are no effective therapies. A potential approach is substrate reduction therapy using inhibitors of glucosylceramide synthase (GCS) to decrease the synthesis of glucosylceramide and related glycosphingolipids that accumulate in the lysosomes. Genz-529468, a blood-brain barrier-permeant iminosugar-based GCS inhibitor, was used to evaluate this concept in a mouse model of Sandhoff disease, which accumulates the glycosphingolipid GM2 in the visceral organs and CNS. As expected, oral administration of the drug inhibited hepatic GM2 accumulation. Paradoxically, in the brain, treatment resulted in a slight increase in GM2 levels and a 20-fold increase in glucosylceramide levels. The increase in brain glucosylceramide levels might be due to concurrent inhibition of the non-lysosomal glucosylceramidase, Gba2. Similar results were observed with NB-DNJ, another iminosugar-based GCS inhibitor. Despite these unanticipated increases in glycosphingolipids in the CNS, treatment nevertheless delayed the loss of motor function and coordination and extended the lifespan of the Sandhoff mice. These results suggest that the CNS benefits observed in the Sandhoff mice might not necessarily be due to substrate reduction therapy but rather to off-target effects

Acqua virtuale nella dieta, nella spesa, nello spreco alimentare

L\u2019atto del cibarsi, nei paesi sviluppati, \ue8 un\u2019azione che mediamente ognuno di noi compie almeno tre volte al giorno ed \ue8 diventato un atto talmente abituale e scontato che non gli si attribuisce pi\uf9 il valore e il peso che meriterebbe, sebbene sia essenziale per la nostra sopravvivenza. Nutrirsi sembra quindi un atto che per molti di noi ha perso valore, e non solo quello economico, ma anche e soprattutto quello etico, sociale, culturale, ambientale e biologico. Questo \ue8 dimostrato dal fatto che a livello europeo il 43% dello spreco alimentare ha luogo a livello domestico. Se tutti noi considerassimo il cibo un bene essenziale per la vita, sicuramente non lo sprecheremmo. Lo spreco viene perpetrato, senza la consapevolezza delle sue conseguenze, anche in termini di spreco di risorse utilizzate per la sua produzione. Forse, al fine di ridurre tale fenomeno, potrebbe essere utile quantificare le ingenti risorse che vengo impiegate. Con questo contributo cercheremo quindi di dare una nuova chiave di lettura dei nostri modelli alimentari, ponendo in risalto che impatto idrico possono avere a seconda degli stili di consumo adottati. Prendendo come riferimento il lavoro di Loius Malassis, che, alla fine degli anni \u201980, classific\uf2 le diete in base al loro modello agronutrizionale (Man), riclassificando i diversi modelli alimentari con dati aggiornati, si cercher\ue0 di fornire una quantificazione dell\u2019impatto idrico delle diete, avvalendoci principalmente dei risultati delle ricerche di Allan e Hoekstra in termini di consumi idrici degli alimenti. In definitiva il contributo ha come obiettivi quello di evidenziare i consumi di acqua virtuale dei differenti modelli agronutrizionali, alla base dei differenti stili di vita e di consumo, ma anche di porre in evidenza come piccole modifiche di questi possono determinare variazioni in termini di impatto idrico e una conseguente riduzione sulla pressione delle risorse idriche mondiali