Article
Biochemistry & Molecular Biology
Alon M. Douek, Mitra Amiri Khabooshan, Jason Henry, Sebastian-Alexander Stamatis, Florian Kreuder, Georg Ramm, Minna-Liisa Anko, Donald Wlodkowic, Jan Kaslin
Summary: MPS IIIA, a pediatric neurological lysosomal storage disease, lacks effective therapy. By creating a zebrafish model of MPS IIIA, researchers found that the sgsh(Delta ex5-6) zebrafish mutant faithfully recapitulates various features of MPS IIIA, providing a valuable resource for gaining insight into MPS IIIA pathobiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Michael Hocquemiller, Laura Giersch, Xin Mei, Amanda L. Gross, Ashley N. Randle, Heather L. Gray-Edwards, Judith A. Hudson, Sophia Todeasa, Lorelei Stoica, Douglas R. Martin, Miguel Sena-Esteves, Karen Aiach, Ralph Laufer
Summary: GM1 gangliosidosis is a rare neurodegenerative disorder caused by GLB1 gene mutations. LYS-GM101 gene therapy has shown potential in preclinical studies and supports further clinical research for the treatment of GM1 gangliosidosis.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Clinical Neurology
Marianna Bugiani, Truus E. M. Abbink, Arthur W. D. Edridge, Lia van der Hoek, Anne E. J. Hillen, Niek P. van Til, Gino V. Hu-A-Ng, Marjolein Breur, Karen Aiach, Philippe Drevot, Michael Hocquemiller, Ralph Laufer, Frits A. Wijburg, Marjo S. van der Knaap
Summary: The AAVance gene therapy trial investigated the intracerebral injection of AAVrh.10 overexpressing human sulfamidase in children with MPSIIIA. Post-treatment MRI monitoring revealed lesions around injection sites. Investigations showed dysfunction of transduced cells close to the injection sites, leading to altered extracellular matrix composition and cystic white matter degeneration. The potential benefit-risk ratio of this therapy will be revealed by the trial results.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Neurosciences
Miguel Gama A. Sosa, Rita De Gasperi, Dylan Pryor, Georgina S. Perez S. Garcia, Gissel M. Perez, Rania Abutarboush, Usmah Kawoos, Seth Hogg, Benjamin Ache, Allison Sowa, Timothy Tetreault, Merina Varghese, David G. Cook, Carolyn W. Zhu, Susan J. Tappan, William G. M. Janssen, Patrick R. Hof, Stephen T. Ahlers, Gregory A. Elder
Summary: In the context of modern war theaters, blast exposures in military operations can lead to the development of various mental health disorders associated with post-traumatic stress disorder symptoms. This study focuses on investigating the late neuropathological events associated with cerebrovascular changes induced by repetitive low-level blast-exposures. The findings suggest that the cerebral vasculature is a major target for blast-induced damage, leading to neurovascular degenerative processes.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Chemistry, Analytical
Jake B. White, Paul J. Trim, Thalia Salagaras, Aaron Long, Peter J. Psaltis, Johan W. Verjans, Marten F. Snel
Summary: Chromatography is commonly used to simplify samples before mass spectrometry analysis, and the use of retention time (RT) for lipid identification is gaining popularity. This study demonstrates a strong correlation in chromatographic separation of lipids with different headgroups but the same fatty acid motive. The correlation is used for interclass RT conversion (IC-RTC), allowing the prediction of RT of one lipid subclass based on another. A glycerophospholipid RT library is built using ECN modeling and IC-RTC, and successfully applied to identify lipid species in a patient cohort undergoing surgery.
ANALYTICAL CHEMISTRY
(2022)
Meeting Abstract
Endocrinology & Metabolism
Nidal Boulos, Zhuchun Wu, Yoonjin Cho, Caroline Mulatya, Maria Fuller, Jerome Ausseil, Luigi M. Pavone, Roberto Giugliani, Michele Fiscella, Marie-Laure Nevoret
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Biochemistry & Molecular Biology
Raed Daher, Nicolas Ducrot, Thibaud Lefebvre, Sofia Zineeddine, Jerome Ausseil, Herve Puy, Zoubida Karim
Summary: This study investigated the relationship between acidosis and iron metabolism in vivo and found evidence of a link between the two. Metabolic acidosis may contribute to the pathologic elevation of serum hepcidin levels in patients with chronic kidney disease. The regulation of ATP4 by iron metabolism is also important for patients with hemochromatosis.
Article
Medicine, Research & Experimental
Karima Habbas, Oktay Cakil, Boglarka Zambo, Ricardos Tabet, Fabrice Riet, Doulaye Dembele, Jean-Louis Mandel, Michael Hocquemiller, Ralph Laufer, Francoise Piguet, Herve Moine
Summary: Fragile X syndrome (FXS) is a common form of familial intellectual disability caused by the lack of RNA-binding protein FMRP. This study demonstrates that DGKk, an mRNA target of FMRP and a regulator of lipid signaling, plays an important role in FXS pathogenesis, and the delivery of modified and FMRP-independent DGKk can correct abnormal lipid signaling and behavioral phenotypes in FXS mice.
EMBO MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Linda Yaker, Abdellah Tebani, Celine Lesueur, Chloe Dias, Vincent Jung, Soumeya Bekri, Ida Chiara Guerrera, Said Kamel, Jerome Ausseil, Agnes Boullier
Summary: This study found that extracellular vesicles (EVs) secreted by macrophages during vascular calcification (VC) can induce inflammatory and oxidative stress responses, exacerbating the calcification of vascular smooth muscle cells (VSMCs).
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Lauren S. Whyte, Celia Fourrier, Sofia Hassiotis, Adeline A. Lau, Paul J. Trim, Leanne K. Hein, Kathryn J. Hattersley, Julien Bensalem, John J. Hopwood, Kim M. Hemsley, Timothy J. Sargeant
Summary: Lysosomal network abnormalities are a significant feature of Alzheimer's disease, and reduced expression of the Hexb gene may lead to related pathological changes and behavioral alterations in an AD model mouse.
IBRO NEUROSCIENCE REPORTS
(2022)
Article
Medicine, Research & Experimental
Michael Hocquemiller, Laura Giersch, Xin Mei, Amanda L. Gross, Ashley N. Randle, Heather L. Gray-Edwards, Judith A. Hudson, Sophia Todeasa, Lorelei Stoica, Douglas R. Martin, Miguel Sena-Esteves, Karen Aiach, Ralph Laufer
Summary: GM1 gangliosidosis is a rare neurodegenerative disorder caused by GLB1 gene mutations. LYS-GM101 gene therapy has shown potential in preclinical studies and supports further clinical research for the treatment of GM1 gangliosidosis.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Leanne K. Winner, Helen Beard, Litsa Karageorgos, Nicholas J. Smith, John J. Hopwood, Kim M. Hemsley
Summary: Acute neuronopathic Gaucher disease is a devastating neurological disorder caused by mutations in the glucocerebrosidase gene, leading to the accumulation of specific lipids. In this study, the pathological changes in GD lamb brain were examined and compared to those in GD patient tissue, confirming the validity of the ovine model.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Sarka Pokorna, Olga Khersonsky, Rosalie Lipsh-Sokolik, Adi Goldenzweig, Rebekka Nielsen, Yacov Ashani, Yoav Peleg, Tamar Unger, Shira Albeck, Orly Dym, Asa Tirosh, Rana Tarayra, Michael Hocquemiller, Ralph Laufer, Shifra Ben-Dor, Israel Silman, Joel L. L. Sussman, Sarel J. J. Fleishman, Anthony H. H. Futerman
Summary: In this study, GCase variants with enhanced stability were generated using the PROSS stability-design algorithm. These variants showed improved enzymatic activity and could be used as an alternative to the recombinant human enzymes for treating Gaucher disease. Additionally, a machine learning-based approach was developed to predict the enzymatic activity of GBA1 gene variants, which could be used to determine disease risk factors in patients carrying rare mutations.
Article
Veterinary Sciences
R. D. Jolly, M. R. Perrott, M. R. Alley, S. A. Hunter, A. Pas, H. Beard, K. M. Hemsley, G. Greaves
Summary: This study investigated the pathogenesis of a disease in takahe (Porphyrio hochstetteri) characterized by intracytoplasmic inclusion bodies in lower motor neurons. Four takahe birds from different wildlife sanctuaries in New Zealand were examined, and two types of inclusion bodies were found in the motor neurons of the spinal cord and brain stem. The larger globoid bodies were found to be endoplasmic reticulum storage disease, while the smaller granular bodies showed misfolded protein entering the lysosomal system via endoplasmic reticulum autophagy. The cause of the disease is likely genetic or predisposed, and has clinical relevance.
NEW ZEALAND VETERINARY JOURNAL
(2023)
Article
Clinical Neurology
Marianna Bugiani, Truus E. M. Abbink, Arthur W. D. Edridge, Lia van der Hoek, Anne E. J. Hillen, Niek P. van Til, Gino V. Hu-A-Ng, Marjolein Breur, Karen Aiach, Philippe Drevot, Michael Hocquemiller, Ralph Laufer, Frits A. Wijburg, Marjo S. van der Knaap
Summary: The AAVance gene therapy trial investigated the intracerebral injection of AAVrh.10 overexpressing human sulfamidase in children with MPSIIIA. Post-treatment MRI monitoring revealed lesions around injection sites. Investigations showed dysfunction of transduced cells close to the injection sites, leading to altered extracellular matrix composition and cystic white matter degeneration. The potential benefit-risk ratio of this therapy will be revealed by the trial results.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Leanne K. Winner, Mary-Louise Rogers, Marten F. Snel, Kim M. Hemsley
Summary: Sanfilippo syndrome is an autosomal recessive inherited disorder that causes dementia in children. Early symptoms include delayed language development, hyperactivity, and insomnia, followed by the loss of acquired skills. There are no approved treatments, and the disease usually leads to death by age 18. Newborn screening for Sanfilippo syndrome would allow for early diagnosis and treatment, but there is a need for tools and biomarkers to provide pre-symptomatic prognosis. This review discusses the development of biomarker assays for Sanfilippo syndrome based on known neuropathological pathways.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Neurosciences
Kim M. Hemsley, Helen Beard, Glyn Chidlow, Teresa Mammone, Leanne K. Winner, Daniel Neumann, Barbara King, Marten F. Snel, Paul J. Trim, Robert J. Casson
Summary: Optical coherence tomography (OCT) is a non-invasive method that can be used to rapidly and quantitatively examine the integrity of the neuroretina. It has been shown that OCT can be used to observe retinal thinning in patients with childhood dementia, and to assess the improvement of retinal structure after treatment. Furthermore, OCT can provide insights into other childhood dementias based on the correlation between retinal and brain degeneration in Sanfilippo syndrome.
EXPERIMENTAL NEUROLOGY
(2024)