Transportation News

Newsletter published by the Texas Department of Transportation for TxDOT employees including information about the organization, projects throughout the state, and other topics related to transportation in Texas

The hidden Niemann-Pick type C patient:Clinical niches for a rare inherited metabolic disease

Background: Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups (clinical niches) have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. Methods: Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. Findings: Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. Conclusions: Several clinical niches have been identified that harbor patients at increased risk of NP-C

The hidden Niemann-Pick type C patient : clinical niches for a rare inherited metabolic disease

BACKGROUND : Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups (“clinical niches”) have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes. METHODS : Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included. FINDINGS : Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches. CONCLUSIONS : Several clinical niches have been identified that harbor patients at increased risk of NP-C.Actelion Pharmaceuticals Ltd., Allschwil, Switzerland. From Actelion Pharmaceuticals Ltd.: travel expenses AC, AD, AP, CD-V, CJH, CL, HHK, MT, MW, MP, MS, PB, OB, SD, SL; research funding AP, CL, CD-V, CJH, FT-B, J-CC, MW, OB, PB, RI, SD, TD, TdK; consultancy fees AP, CJH, CL, HHK, MT, MW, OB, PB, SL; speaker honoraria CD-V, MP, MS, PB, SD. MA has received speaker honoraria and travel expenses from Abbvie, TEVA, and UCB. J-CC has received speaker honoraria from Abbvie, travel grants from Abbvie, research funding from, Ipsen, and the Michael J Fox Foundation, and consultancy fees from BMS, Zambon, Pfizer, Amarantus, Clevexel, and Abbvie. CD-V has received research grants, investigator fees, speaker honoraria, and travel expenses from Sanofi Genzyme, Orphan Europe, and Nutricia. SD has received research funding from TEVA. CJH is Director of FYMCA Medical Ltd., has received consultancy fees and travel expenses from Alexion, Amicus, Biomarin, Inventiva, Sanofi Genzyme, and Shire, and has undertaken paid research on behalf of Amicus, Biomarin, Sanofi Genzyme and Shire. SL has received consultancy fees and travel expenses from TEVA, Boehringer, Gruenenthal, and UCB6e. AP has received research funding, consultancy fees and travel expenses from Eli-Lilly, GE Health, and Lundbeck. CT has received speaker honoraria and travel expenses from Abbvie, Zambon, TEVA, and UCB. CV and SK are employees of Actelion Pharmaceuticals Ltd.http://www.tandfonline.com/loi/icmo202018-03-02hj2018Paediatrics and Child Healt

LifeTime and improving European healthcare through cell-based interceptive medicine

AUTEURS : LifeTime Community Working GroupsInternational audienceHere we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade

LifeTime and improving European healthcare through cell-based interceptive medicine

LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.We would like to acknowledge all participants that have attended and contributed to LifeTime meetings and workshops through many exciting presentations and discussions. We thank Johannes Richers for artwork. LifeTime has received funding from the European Unionʼs Horizon 2020 research and innovation framework programme under Grant agreement 820431