Article
Biochemistry & Molecular Biology
Owen Daly, Azita Josefine Mahiny, Sara Majeski, Kevin McClintock, Julia Reichert, Gabor Boros, Gabor Tamas Szabo, Jonas Reinholz, Petra Schreiner, Steve Reid, Kieu Lam, Marlen Lepper, Melanie Adler, Tracy Meffen, James Heyes, Katalin Kariko, Pete Lutwyche, Irena Vlatkovic
Summary: This study describes a novel therapeutic approach for the treatment of argininosuccinic aciduria (ASA), using nucleoside-modified messenger RNA (modRNA) formulated in lipid nanoparticles (LNP). Multiple modifications of ASL mRNA were tested and resulted in robust ASL protein expression in vitro and in vivo. The lead therapeutic candidate, LNP-ASL CDS2, significantly improved the survival of mice in an ASL-deficient mouse model. These findings demonstrate the considerable potential of LNP-formulated modified ASL-encoding mRNA as a treatment for ASA.
Review
Clinical Neurology
Michael Benatar, Joanne Wuu, Caroline McHutchison, Ronald B. Postuma, Bradley F. Boeve, Ronald Petersen, Christopher A. Ross, Howard Rosen, Jalayne J. Arias, Stephanie Fradette, Michael P. McDermott, Jeremy Shefner, Christine Stanislaw, Sharon Abrahams, Stephanie Cosentino, Peter M. Andersen, Richard S. Finkel, Volkan Granit, Anne-Laure Grignon, Jonathan D. Rohrer, Corey T. McMillan, Murray Grossman, Ammar Al-Chalabi, Martin R. Turner
Summary: Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. Advances in other neurodegenerative diseases provide valuable insights and highlight opportunities for discovery in ALS. Biomarkers play a critical role in studying pre-symptomatic ALS and are essential for early therapeutic intervention and disease prevention.
Article
Clinical Neurology
Nour Elkhateeb, Giorgia Olivieri, Barbara Siri, Stewart Boyd, Karolina M. Stepien, Reena Sharma, Andrew A. M. Morris, Thomas Hartley, Laura Crowther, Stephanie Grunewald, Maureen Cleary, Helen Mundy, Anupam Chakrapani, Robin Lachmann, Elaine Murphy, Saikat Santra, Mari-Liis Uudelepp, Mildrid Yeo, Isaac Bernhardt, Sniya Sudakhar, Alicia Chan, Philippa Mills, Debora Ridout, Paul Gissen, Carlo Dionisi-Vici, Julien Baruteau
Summary: This study aims to characterize epilepsy in argininosuccinic aciduria and correlate it with clinical, biochemical, radiological, and electroencephalographic data. It found that epilepsy is frequent and polymorphic in argininosuccinic aciduria, and is associated with neurodevelopmental comorbidities. Prognostic factors for pharmacoresistance in epilepsy were also identified.
Article
Computer Science, Interdisciplinary Applications
Anna Zan, Zhong-Ru Xie, Yi-Chen Hsu, Yu-Hao Chen, Tsung-Hsien Lin, Yong-Shan Chang, Kuan Y. Chang
Summary: This study demonstrated the possibility of predicting flu infection based on gene expression, with gene expression reflecting host immunity strength. DeepFlu, a prognostic tool, can moderately recognize individuals susceptible to the flu and may help prevent the spread of influenza.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2022)
Article
Endocrinology & Metabolism
Naiara G. Bediaga, Connie S. N. Li-Wai-Suen, Michael J. Haller, Stephen E. Gitelman, Carmella Evans-Molina, Peter A. Gottlieb, Markus Hippich, Anette-Gabriele Ziegler, Ake Lernmark, Linda A. DiMeglio, Diane K. Wherrett, Peter G. Colman, Leonard C. Harrison, John M. Wentworth
Summary: The study developed a simplified prediction tool that accurately predicts disease progression in individuals with type 1 diabetes based on a single blood draw. The tool showed good validity across different high-risk populations.
Article
Endocrinology & Metabolism
Sonam Gurung, Saketh Karamched, Dany Perocheau, Kiran K. Seunarine, Tom Baldwin, Haya Al-Rashidi, Loukia Touramanidou, Claire Duff, Nour Elkhateeb, Karolina M. Stepien, Reena Sharma, Andrew Morris, Thomas Hartley, Laura Crowther, Stephanie Grunewald, Maureen Cleary, Helen Mundy, Anupam Chakrapani, Spyros Batzios, James Davison, Emma Footitt, Karin Tuschl, Robin Lachmann, Elaine Murphy, Saikat Santra, Mari-Liis Uudelepp, Mildrid Yeo, Patrick F. Finn, Alex Cavedon, Summar Siddiqui, Lisa Rice, Paolo G. V. Martini, Andrea Frassetto, Simon Heales, Philippa B. Mills, Paul Gissen, Jonathan D. Clayden, Christopher A. Clark, Simon Eaton, Tammy L. Kalber, Julien Baruteau
Summary: Argininosuccinate lyase (ASL) is an important enzyme involved in the urea cycle and NO biosynthesis. Deficiency of ASL can lead to a rare disease called argininosuccinic aciduria (ASA), which is characterized by hyperammonemia and NO deficiency. In a retrospective study conducted in the UK, researchers identified 60 patients with ASA and investigated the neurodegenerative phenotype associated with the disease. The study found that movement disorders and abnormal behavior were prevalent in ASA patients, and neuroimaging showed abnormal features in the basal ganglia. However, further research is needed to fully understand the pathophysiology of ASA-related neurodegeneration.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Oncology
Ian S. Miller, Sonja Khan, Liam P. Shiels, Sudipto Das, Alice C. O' Farrell, Kate Connor, Adam Lafferty, Bruce Moran, Claudio Isella, Paul Loadman, Emer Conroy, Susan Cohrs, Roger Schibli, Robert S. Kerbel, William M. Gallagher, Elisabetta Marangoni, Kathleen Bennett, Darran P. O' Connor, Roisin M. Dwyer, Annette T. Byrne
Summary: The study showed that aspirin could delay metastasis in HER2+ breast cancer and reduce the growth of primary tumors in HER2+/TNBC. However, no survival benefit was observed in aspirin pre-treated animals that also received standard of care chemotherapy. Aspirin altered breast tumor biology through various mechanisms but may not be an effective chemopreventive agent in HER2+ or TNBC setting.
Article
Radiology, Nuclear Medicine & Medical Imaging
Haishan Qiu, Chao Wu, Jiahui Liang, Manshi Hu, Yingqian Chen, Zihuan Huang, Zhiyun Yang, Jing Zhao, Jianping Chu
Summary: This study aims to investigate the structural alterations in the brain of SCA3 patients and their correlations with ATXN3 expression and disease severity. The findings suggest that white matter damage occurs before the onset of ataxia in pre-symptomatic patients, mainly in the cerebellar peduncles. In the advanced stage, the damage follows a caudal-rostral pattern. The study also reveals brainstem volumetric reduction and cerebellar and basal ganglia atrophy, which are partially explained by ATXN3 overexpression. The bilateral pallidum, brainstem, and cerebellar peduncles show significant effect sizes. These alterations are correlated with the severity of the disease and the volume of the pons appears to be a promising imaging biomarker for longitudinal study.
EUROPEAN RADIOLOGY
(2023)
Article
Pediatrics
Maria P. Zuza, Genaro Gerbaudo, Sergio O. Molina, Marcela Pereyra
Summary: Urea cycle defects are inborn errors of metabolism caused by enzyme deficiencies, leading to ammonia accumulation. Clinical manifestations can be early or late onset, with clinical suspicion often lacking in neonates. Increased plasma ammonia levels can indicate a urea cycle defect, and early diagnosis is crucial for effective treatment, with disorders like argininosuccinic aciduria being common and requiring early detection.
ARCHIVOS ARGENTINOS DE PEDIATRIA
(2021)
Article
Endocrinology & Metabolism
Sarah C. Shuck, Peter Achenbach, Bart O. Roep, John S. Termini, Carlos Hernandez-Castillo, Christiane Winkler, Andreas Weiss, Anette-Gabriele Ziegler
Summary: The study found that serum levels of MG-AGEs were associated with the rate of progression to stage 3 type 1 diabetes, with lower levels increasing the risk of progression. This provides a potential new clinical biomarker for determining the rate of disease progression and points to contributing metabolic pathways.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Editorial Material
Clinical Neurology
Richard S. Finkel, Michael Benatar
Summary: Finkel and Benatar discuss the ambiguity of the term 'pre-symptomatic' in characterizing infants at genetic risk for spinal muscular atrophy, and propose a new conceptual framework.
Article
Medicine, General & Internal
Chalotte W. Nicolajsen, Mette Sogaard, Martin Jensen, Nikolaj Eldrup, Torben B. Larsen, Samuel Z. Goldhaber, Christian-Alexander Behrendt, Peter B. Nielsen
Summary: This study aims to evaluate the effect of antiplatelet therapy on the risk of ischemic events and bleeding in patients with abdominal aortic aneurysms without symptomatic atherosclerotic vascular disease.
Article
Biochemistry & Molecular Biology
Madalena Barroso, Marcus Gertzen, Alexandra F. Puchwein-Schwepcke, Heike Preisler, Andreas Sturm, Dunja D. Reiss, Marta K. Danecka, Ania C. Muntau, Soren W. Gersting
Summary: By using different biochemical and biophysical methods, we conducted a parallel analysis on 13 GCDH missense variants and found that these variants could lead to conformational changes in the protein, which would affect the biochemical phenotype. This study reveals the classification of GA1 as a protein-misfolding disorder and supports research on new therapeutic strategies targeting this molecular disease phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Marina Makri, Mara Gkioka, Despina Moraitou, Liana Fidani, Thomas Tegos, Magdalini Tsolaki
Summary: The goal of this study was to examine the psychometric properties of a questionnaire for assessing attitudes, barriers, and motivations to pre-symptomatic AD screening. The study found four factors, including perceived harms of testing, acceptance of testing, perceived benefits of testing, and the need for knowledge. The overall questionnaire demonstrated good internal consistency.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
D. Molina-Mateo, B. P. Valderrama, R. V. Zarate, S. Hidalgo, J. Tamayo-Leiva, A. Soto-Gonzalez, S. Guerra-Ayala, V. Arriagada-Vera, C. Oliva, B. Diez, J. M. Campusano
Summary: Parkinson's disease is a neurodegenerative disorder characterized by motor alterations. Recent studies have shown that this disorder involves other organs like the gut, and the gut microbiota plays a key role in the communication between these organs. In a Drosophila model for Parkinson's disease, it has been found that alterations in the gut microbiota can have beneficial effects on the progression of the disease and age-dependent motor impairments.
Article
Endocrinology & Metabolism
Julien Baruteau, Carmen Diez-Fernandez, Shaul Lerner, Giusy Ranucci, Paul Gissen, Carlo Dionisi-Vici, Sandesh Nagamani, Ayelet Erez, Johannes Haberle
JOURNAL OF INHERITED METABOLIC DISEASE
(2019)
Article
Endocrinology & Metabolism
Femke Molema, Florian Gleich, Peter Burgard, Ans T. van der Ploeg, Marshall L. Summar, Kimberly A. Chapman, Ivo Baric, Allan M. Lund, Stefan Koelker, Monique Williams, F. Hoerster, A. M. Jelsig, P. de Lonlay, F. A. Wijburg, A. Bosch, P. Freisinger, R. Posset, P. Augoustides-Savvopoulou, P. Avram, C. Deleanu, M. R. Baumgartner, J. Haberle, J. Blasco-Alonso, A. B. Burlina, L. Rubert, A. Garcia Cazorla, E. Cortes i Saladelafont, C. Dionisi-Vici, D. Martinelli, D. Dobbelaere, K. Mention, S. Grunewald, A. Chakrapani, W. -L. Hwu, Y. -H. Chien, N. -C. Lee, D. Karall, S. Scholl-Buergi, R. Lachmann, C. De Laet, S. Matsumoto, L. de Meirleir, C. Muehlhausen, M. Schiff, L. Pena-Quintana, M. Djordjevic, A. Sarajlija, J. Sykut-Cegielska, A. Wisniewska, E. Leao-Teles, S. Alves, R. Vara, I. Vives-Pinera, D. G. Ortega, A. Morris, J. Zeman, T. Honzik, B. Chabrol, F. Arnaudo, A. Cano, N. Thompson, F. Eyskens, M. Lindner, N. Luesebrink, A. Jalan, E. Sokal, V. Legros, M. C. Nassogne
JOURNAL OF INHERITED METABOLIC DISEASE
(2019)
Article
Endocrinology & Metabolism
Gabriella Allegri, Sereina Deplazes, Nicole Rimann, Benjamin Causton, Tanja Scherer, Jonathan W. Leff, Carmen Diez-Fernandez, Anna Klimovskaia, Ralph Fingerhut, Jakub Krijt, Viktor Kozich, Jean-Marc Nuoffer, Hiu M. Grisch-Chan, Beat Thony, Johannes Haberle
JOURNAL OF INHERITED METABOLIC DISEASE
(2019)
Article
Endocrinology & Metabolism
Suhail Khoja, Matthew Nitzahn, Brian Truong, Jenna Lambert, Brandon Willis, Gabriella Allegri, Veronique Rufenacht, Johannes Haberle, Gerald S. Lipshutz
JOURNAL OF INHERITED METABOLIC DISEASE
(2019)
Article
Endocrinology & Metabolism
Raghuraman C. Srinivasan, Mihaela Zabulica, Christina Hammarstedt, Tingting Wu, Roberto Gramignoli, Kristina Kannisto, Ewa Ellis, Ahmad Karadagi, Ralph Fingerhut, Gabriella Allegri, Veronique Rufenacht, Beat Thony, Johannes Haberle, Jean-Marc Nuoffer, Stephen C. Strom
JOURNAL OF INHERITED METABOLIC DISEASE
(2019)
Article
Genetics & Heredity
M. E. Rubio-Gozalbo, M. Haskovic, A. M. Bosch, B. Burnyte, A. I. Coelho, D. Cassiman, M. L. Couce, C. Dawson, D. Demirbas, T. Derks, F. Eyskens, M. T. Forga, S. Grunewald, J. Haberle, M. Hochuli, A. Hubert, H. H. Huidekoper, P. Janeiro, J. Kotzka, I. Knerr, P. Labrune, Y. E. Landau, J. G. Langendonk, D. Moeslinger, D. Mueller-Wieland, E. Murphy, K. Ounap, D. Ramadza, I. A. Rivera, S. Scholl-Buergi, K. M. Stepien, A. Thijs, C. Tran, R. Vara, G. Visser, R. Vos, M. de Vries, S. E. Waisbren, M. M. Welsink-Karssies, S. B. Wortmann, M. Gautschi, E. P. Treacy, G. T. Berry
ORPHANET JOURNAL OF RARE DISEASES
(2019)
Article
Endocrinology & Metabolism
Sapna Gupta, Lorena Gallego-Villar, Liqun Wang, Hyung-Ok Lee, Gheyath Nasrallah, Nader Al-Dewik, Johannes Haberle, Beat Thony, Henk J. Blom, Tawfeg Ben-Omran, Warren D. Kruger
JOURNAL OF INHERITED METABOLIC DISEASE
(2019)
Article
Multidisciplinary Sciences
Brian Truong, Gabriella Allegri, Xiao-Bo Liu, Kristine E. Burke, Xuling Zhu, Stephen D. Cederbaum, Johannes Haberle, Paolo G. V. Martini, Gerald S. Lipshutz
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Editorial Material
Medicine, General & Internal
S. Arora, M. V. Padma Srivastava, M. B. Singh, V. Goyal, J. Haberle, Shalimar, N. Gupta, A. Prabhakar, B. Aggarwal, A. Agarwal, V. Y. Vishnu
QJM-AN INTERNATIONAL JOURNAL OF MEDICINE
(2020)
Article
Pediatrics
Tim R. J. Aeppli, Daisy Rymen, Gabriella Allegri, Peter K. Bode, Johannes Haeberle
EUROPEAN JOURNAL OF PEDIATRICS
(2020)
Letter
Genetics & Heredity
Johannes Haeberle, Veronique Ruefenacht
GENETICS IN MEDICINE
(2020)
Article
Multidisciplinary Sciences
Michael Dietachmayr, Abirami Rathakrishnan, Oleksandra Karpiuk, Felix von Zweydorf, Thomas Engleitner, Vanesa Fernandez-Saiz, Petra Schenk, Marius Ueffing, Roland Rad, Martin Eilers, Christian Johannes Gloeckner, Katharina Clemm von Hohenberg, Florian Bassermann
NATURE COMMUNICATIONS
(2020)
Article
Genetics & Heredity
Johannes Haeberle, Marvin B. Moore, Nantaporn Haskins, Veronique Rufenacht, Dariusz Rokicki, Estela Rubio-Gozalbo, Mendel Tuchman, Nicola Longo, Mark Yandell, Ashley Andrews, Nicholas AhMew, Ljubica Caldovic
Summary: N-acetylglutamate synthase deficiency is an autosomal recessive urea cycle disorder that can be effectively treated with N-carbamylglutamate. Research suggests that analyzing noncoding regions of NAGS and other urea cycle genes could reveal molecular causes of disease and identify novel regulators of ureagenesis.
Article
Obstetrics & Gynecology
Shruti Bajaj, Uday Joglekar, Anil Jalan, Johannes Haberle, Veronique Ruefenacht
Summary: This case highlights the importance of genetic counseling for couples who have lost a child to a genetic disorder, and the significance of post-mortem genetic analysis for confirming diagnoses in future pregnancies. It also underscores the necessity of prenatal testing and DNA banking in fatal genetic disorders to enable effective genetic counseling for future pregnancies.
JOURNAL OF FETAL MEDICINE
(2021)
Article
Nutrition & Dietetics
Bigna K. Bolsterli, Eugen Boltshauser, Luigi Palmieri, Johannes Spenger, Michaela Brunner-Krainz, Felix Distelmaier, Peter Freisinger, Tobias Geis, Andrea L. Gropman, Johannes Haberle, Julia Hentschel, Bruno Jeandidier, Daniela Karall, Boris Keren, Annick Klabunde-Cherwon, Vassiliki Konstantopoulou, Raimund Kottke, Francesco M. Lasorsa, Christine Makowski, Cyril Mignot, Ruth O'Gorman Tuura, Vito Porcelli, Rene Santer, Kuntal Sen, Katja Steinbruecker, Steffen Syrbe, Matias Wagner, Andreas Ziegler, Thomas Zoeggeler, Johannes A. Mayr, Holger Prokisch, Saskia B. Wortmann
Summary: Defects in the mitochondrial malate aspartate shuttle system and mitochondrial pyruvate carrier 1 are associated with neurological phenotypes and hepatopathic-neuropsychiatric phenotypes. Ketogenic diets and carbohydrate-restricted/fat-enriched diets are effective interventions. Early (genetic) diagnosis is crucial for initiating proper treatment.