Article
Health Care Sciences & Services
Min-Sun Kim, Aram Yang, Eu-Seon Noh, Chiwoo Kim, Ga Young Bae, Han Hyuk Lim, Hyung-Doo Park, Sung Yoon Cho, Dong-Kyu Jin
Summary: This study analyzed the genetic and clinical characteristics of MPS III patients in Korea for the first time, revealing the natural history of the disease. The findings contribute to early diagnosis, timely management, and evaluation of treatment outcomes in future clinical trials for MPS III.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Immunology
Xuefang Pan, Mahsa Taherzadeh, Poulomee Bose, Rachel Heon-Roberts, Annie L. A. Nguyen, TianMeng Xu, Camila Para, Yojiro Yamanaka, David A. Priestman, Frances M. Platt, Shaukat Khan, Nidhi Fnu, Shunji Tomatsu, Carlos R. Morales, Alexey Pshezhetsky
Summary: The majority of MPS IIIC patients have missense variants causing misfolding of HGSNAT, which can be potentially treated with pharmacological chaperones. A novel mouse model expressing a misfolded HGSNAT variant shows deficits in memory and neuroimmune response, which can be rescued by treatment with a chaperone, glucosamine.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Endocrinology & Metabolism
Arunabha Ghosh, Stewart Rust, Kia Langford-Smith, Daniel Weisberg, Maria Canal, Catherine Breen, Michelle Hepburn, Karen Tylee, Frederic M. Vaz, Andy Vail, Frits Wijburg, Claire O'Leary, Helen Parker, J. Ed Wraith, Brian W. Bigger, Simon A. Jones
Summary: This study found that high doses of genistein aglycone therapy did not lead to clinically meaningful reductions in cerebrospinal fluid heparan sulfate concentrations in Sanfilippo syndrome (mucopolysaccharidosis type III), but there was a statistically significant reduction in urinary glycosaminoglycan levels. Other biochemical and clinical parameters showed no significant differences between the two study groups.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Medical Laboratory Technology
Hsuan-Chieh Liao, Rhona Jack, Anna I. Scott
Summary: The developed LC-MS/MS assay for measuring residual GALC activity in leukocytes provides a valuable tool for diagnosing Krabbe disease. With excellent stability and linear detection capabilities, the assay can effectively differentiate between different cases and carriers of the disease.
CLINICA CHIMICA ACTA
(2021)
Article
Endocrinology & Metabolism
Yingjun Liang, Xiaolan Gao, Deyun Lu, Huiwen Zhang, Zhang
Summary: This study analyzed the clinical, biochemical, and genetic characteristics of ten Chinese MPS IIIC patients from eight families. The mean age at symptom onset was 4.2 years old, and the mean age at diagnosis was 7.6 years old, suggesting a delay in diagnosis. The most common presenting symptoms were speech deterioration, followed by mental deterioration, hyperactivity, and hepatomegaly. All mutant alleles of the patients were identified, including eleven different HGSNAT variants, with the most common one being a previously reported variant.
METABOLIC BRAIN DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Patryk Lipinski, Krzysztof Szczaluba, Piotr Buda, Ekaterina Y. Zakharova, Galina Baydakova, Agnieszka Lugowska, Agnieszka Rozdzynska-Swiatkowska, Zuzanna Cyske, Grzegorz Wegrzyn, Agnieszka Pollak, Rafal Ploski, Anna Tylki-Szymanska
Summary: This article reports a Polish MPS-PS patient with a novel VPS33A gene variant and new clinical features. Functional analysis revealed some related biomarkers, and comparison with other cases helped broaden understanding of the disease phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Rutaba Gul, Sabika Firasat, Mikkel Schubert, Asmat Ullah, Elionora Pena, Anne C. B. Thuesen, Mulazim Hussain, Frederik F. Staeger, Anette P. Gjesing, Anders Albrechtsen, Torben Hansen
Summary: The aim of this study was to identify novel genes and pathogenic variants in families from diverse regions of Pakistan with clinically diagnosed mucopolysaccharidosis type I and mucopolysaccharidosis type II. Whole genome sequencing revealed ten novel and six previously reported variants in lysosomal storage disorders-associated genes, as well as a novel candidate gene for lysosomal storage disorder-like phenotypes. The presence of multigenic inheritance in several families highlights the importance of searching for homozygous pathogenic variants in multiple genes, especially in consanguineous families.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
Wei Huang, Yu-Shan Cheng, Shu Yang, Manju Swaroop, Miao Xu, Wenwei Huang, Wei Zheng
Summary: MPS IIIB is a lysosomal disease caused by mutations in the NAGLU gene, with no effective treatment currently available. The study showed that MPS IIIB neural stem cells and neurons can serve as a disease model system for evaluating drug efficacy and compound screening for drug development.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Jennifer T. Saville, Ainslie L. K. Derrick-Roberts, Chantelle McIntyre, Maria Fuller
Summary: The study shows that gene therapy for MPS IIIA in mice can alleviate some symptoms, but cognitive impairments persist in older individuals, likely due to downstream consequences of heparan sulfate affecting neurological functions.
HUMAN GENE THERAPY
(2021)
Article
Neurosciences
Malabendu Jana, Debashis Dutta, Jit Poddar, Kalipada Pahan
Summary: In this study, gemfibrozil was found to alleviate disease pathology, reduce neuroinflammation, restore the level of TFEB, and decrease the accumulation of SCMAS in an animal model of JNCL. Gemfibrozil treatment also improved locomotor activities. These findings suggest that PPARa activation may be beneficial for JNCL and gemfibrozil may be repurposed for its treatment.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Kleopatra Pericleous, Chantelle McIntyre, Maria Fuller
Summary: In this study, a set of behavior tests were evaluated for their reliability in assessing disease progression in the MPS IIIA mouse model. The results showed that the water cross-maze, hind-limb gait, nest building, and burrowing tests are promising assessments that accurately reflect the disease progression in MPS IIIA mice and mimic the human disease.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2023)
Article
Genetics & Heredity
Erin T. Strovel, Kristina Cusmano-Ozog, Tim Wood, Chunli Yu
Summary: Assays that measure lysosomal enzyme activity are crucial for diagnosing and screening lysosomal storage disorders. This document provides guidance for clinical enzyme testing, including test performance variables and the need for follow-up molecular testing.
GENETICS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Frederick James Ashby, Evelyn J. Castillo, Yan Ludwig, Natalia K. Andraka, Cong Chen, Julia C. Jamieson, Nadia Kabbej, John D. Sommerville, Jose I. Aguirre, Coy D. Heldermon
Summary: This study identifies osteogenic manifestations in MPS IIIB mouse model, which could serve as potential biomarkers for preclinical treatment of MPS IIIB.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Kalliopi Sofou, Kolja Meier, Leslie E. Sanderson, Debora Kaminski, Laia Montoliu-Gaya, Emma Samuelsson, Maria Blomqvist, Lotta Agholme, Jutta Gaertner, Chris Muehlhausen, Niklas Darin, Tahsin Stefan Barakat, Lars Schlotawa, Tjakko van Ham, Jorge Asin Cayuela, Fredrik H. Sterky
Summary: Patients with lysosomal storage disease-like symptoms were found to have homozygous mutations in VPS16, resulting in impaired cellular functions such as transferrin uptake and lysosomal accumulation, which were rescued by re-expression of VPS16. Disrupted vps16 expression in zebrafish led to developmental defects and similar lysosomal and autophagosomal accumulation in the brain. This expands the understanding of diseases resulting from mutations in HOPS/CORVET subunits.
EMBO MOLECULAR MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Koji Matsuhisa, Kazunori Imaizumi
Summary: MPS II is a disorder caused by dysfunction of IDS, resulting in mental retardation and systemic symptoms. Current therapies have limitations, while misfolding and degradation of IDS mutants play crucial roles in the disease progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Endocrinology & Metabolism
Barbara King, Neil R. Marshall, Sofia Hassiotis, Paul J. Trim, Justin Tucker, Kathryn Hattersley, Marten F. Snel, Robert D. Jolly, John J. Hopwood, Kim M. Hemsley
JOURNAL OF INHERITED METABOLIC DISEASE
(2017)
Article
Neurosciences
Helen Beard, Sofia Hassiotis, Wei-Ping Gai, Emma Parkinson-Lawrence, John J. Hopwood, Kim M. Hemsley
EXPERIMENTAL NEUROLOGY
(2017)
Article
Behavioral Sciences
Lauren S. Whyte, Kim M. Hemsley, Adeline A. Lau, Sofia Hassiotis, Takashi Saito, Takaomi C. Saido, John J. Hopwood, Timothy J. Sargeant
BEHAVIOURAL BRAIN RESEARCH
(2018)
Article
Neurosciences
Dani L. Webber, Amanda Choo, Laura J. Hewson, Paul J. Trim, Marten F. Snel, John J. Hopwood, Robert Richard, Kim M. Hemsley, Louise O'Keefe
EXPERIMENTAL NEUROLOGY
(2018)
Article
Endocrinology & Metabolism
Adeline A. Lau, Sarah J. Tamang, Kim M. Hemsley
JOURNAL OF INHERITED METABOLIC DISEASE
(2018)
Article
Biochemistry & Molecular Biology
Qi Qi He, Paul J. Trim, Adeline A. Lau, Barbara M. King, John J. Hopwood, Kim M. Hemsley, Marten F. Snel, Vito Ferro
ACS CHEMICAL NEUROSCIENCE
(2019)
Article
Neurosciences
Lauren S. Whyte, Sofia Hassiotis, Kathryn J. Hattersley, Kim M. Hemsley, John J. Hopwood, Adeline A. Lau, Timothy J. Sargeant
Article
Clinical Neurology
Adam B. O'Connell, Timothy R. Kuchel, Sunthara R. Perumal, Victoria Sherwood, Daniel Neumann, John W. Finnie, Kim M. Hemsley, A. Jennifer Morton
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2020)
Article
Medicine, Research & Experimental
Michael Hocquemiller, Kim M. Hemsley, Meghan L. Douglass, Sarah J. Tamang, Daniel Neumann, Barbara M. King, Helen Beard, Paul J. Trim, Leanne K. Winner, Adeline A. Lau, Marten F. Snel, Cathy Gomila, Jerome Ausseil, Xin Mei, Laura Giersch, Mark Plavsic, Ralph Laufer
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2020)
Article
Endocrinology & Metabolism
Meghan L. Douglass, Helen Beard, Andrew Shoubridge, Nazzmer Nazri, Barbara King, Paul J. Trim, Stephen K. Duplock, Marten F. Snel, John J. Hopwood, Kim M. Hemsley
Summary: Lysosomal dysfunction may play a role in neurodegenerative disorders like Parkinson's disease. Mutations in genes encoding lysosomal enzymes have been associated with PD, and studies on mice with a Sgsh gene mutation revealed impaired behavior and brain structure, but no overt disease lesions associated with PD or other neurodegenerative disorders were observed.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Neurosciences
Helen Beard, Glyn Chidlow, Daniel Neumann, Nazzmer Nazri, Meghan Douglass, Paul J. Trim, Marten F. Snel, Robert J. Casson, Kim M. Hemsley
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2020)
Article
Veterinary Sciences
R. D. Jolly, K. E. Dittmer, B. R. Jones, A. J. Worth, K. G. Thompson, A. C. Johnstone, D. N. Palmer, N. S. Van de Water, K. M. Hemsley, D. J. Garrick, B. G. Winchester, S. U. Walkley
Summary: In the past 50 years, there have been significant advances in knowledge and technology regarding genetic diseases, enabling more cost-effective ways to control these diseases. Research on genetic diseases of animals at Massey University has made a significant contribution to veterinary medicine, provided new biological knowledge, and advanced our understanding of similar disorders in human patients.
NEW ZEALAND VETERINARY JOURNAL
(2021)
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)
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)