Article
Biochemistry & Molecular Biology
Nicoletta Di Giorgi, Antonella Cecchettini, Elena Michelucci, Giovanni Signore, Elisa Ceccherini, Francesco Ferro, Elena Elefante, Chiara Tani, Chiara Baldini, Silvia Rocchiccioli
Summary: In this study, mass spectrometry was used to analyze the salivary proteomics of patients with established primary Sjogren's syndrome (pSS) and patients with pre-clinical SS. A common protein signature was identified in their salivary fluid. Differential expression of inflammatory, immunity-related, and acinar proteins suggests that saliva may reflect exocrine gland inflammation in the early phases of the disease. Salivary proteomics can be a valuable tool for identifying reliable biomarkers for SS, even in the preclinical phase of the disease.
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)
Review
Pharmacology & Pharmacy
Nabil A. Alhakamy, David T. Curiel, Cory J. Berkland
Summary: This passage discusses the development of gene therapy technologies, including types, delivery methods, editing technologies, regulatory affairs, clinical trials, approved products, and future goals, emphasizing global advances in gene therapy research. Information on gene therapy clinical trials and approved products developed between 1988 and 2020 was systematically collated by scanning over 46,000 records. The medical and market acceptance of transformative gene therapy technologies are gradually increasing with a significant rise in the number of gene therapy clinical trials and approved products.
DRUG DISCOVERY TODAY
(2021)
Review
Biochemistry & Molecular Biology
Juuso Paajanen, Raphael Bueno, Assunta De Rienzo
Summary: Pleural mesothelioma is a rare and aggressive disease associated with asbestos exposure. Current systemic therapies have limited efficacy, and there are no predictive biomarkers for targeted therapies in clinical use. However, recent advances in PM genetics provide optimism for future treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Theodora Markati, Jessica Duis, Laurent Servais
Summary: This review discusses the current therapeutic approaches for Angelman syndrome, including gene and enzyme replacement therapies, targeting non-coding RNA, and compounds targeting molecular pathways. The future of Angelman syndrome treatment looks promising with potentially more than five disease-modifying treatments at clinical testing by 2022-2023, but challenges such as safety and efficacy need to be addressed, along with a need for improved clinical trial readiness.
EXPERT OPINION ON INVESTIGATIONAL DRUGS
(2021)
Review
Genetics & Heredity
Nicole Muschol, Roberto Giugliani, Simon A. Jones, Joseph Muenzer, Nicholas J. C. Smith, Chester B. Whitley, Megan Donnell, Elise Drake, Kristina Elvidge, Lisa Melton, Cara O'Neill
Summary: Sanfilippo syndrome is a rare, complex, and progressive neurodegenerative lysosomal storage disorder characterized by childhood dementia. The clinical management of these patients requires a multidisciplinary team with experience in neurodegenerative disorders, but there is a lack of global clinical care guidelines. A literature review was conducted to evaluate the current evidence and identify gaps, resulting in a document that provides evidence-based recommendations for the management of Sanfilippo syndrome.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Rujia Zhong, Theresa Schimanski, Feng Zhang, Huan Lan, Alyssa Hohn, Qiang Xu, Mengying Huang, Zhenxing Liao, Lin Qiao, Zhen Yang, Yingrui Li, Zhihan Zhao, Xin Li, Lena Rose, Sebastian Albers, Lasse Maywald, Jonas Muller, Hendrik Dinkel, Ardan Saguner, Johannes W. G. Janssen, Narasimha Swamy, Yannick Xi, Siegfried Lang, Mandy Kleinsorge, Firat Duru, Xiaobo Zhou, Sebastian Diecke, Lukas Cyganek, Ibrahim Akin, Ibrahim El-Battrawy
Summary: This study establishes a cellular model of Brugada syndrome (BrS) with a CACNB2 variant and reveals the pathogenic mechanism of this variant. It also demonstrates that bisoprolol and quinidine can effectively treat BrS with this variant.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Mohammad A. Rafi, Paola Luzi, David A. Wenger
Summary: This study demonstrates that treating Krabbe disease with high dose AAVrh10 without the need for blood stem cell transplantation can result in significant therapeutic effects, which may have potential applications in the treatment of human Krabbe disease patients.
Article
Medicine, Research & Experimental
Susana Navarro, Oscar Quintana-Bustamante, Rebeca Sanchez-Dominguez, Sergio Lopez-Manzaneda, Isabel Ojeda-Perez, Aida Garcia-Torralba, Omaira Alberquilla, Kenneth Law, Brian C. Beard, Antonella Bastone, Michael Rothe, Mariela Villanueva, Juan C. Ramirez, Sara Fananas-Baquero, Virginia Nieto-Romero, Andrea Molinos-Vicente, Sonia Gutierrez, Eileen Nicoletti, Maria Garcia-Bravo, Juan A. Bueren, Jonathan D. Schwartz, Jose-Carlos Segovia
Summary: Pyruvate kinase deficiency is a rare genetic disorder causing hemolytic anemia, potentially fatal in some cases. Allogeneic stem cell transplantation has shown potential as a treatment, but is limited by donor availability, toxicity, and incomplete engraftment.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Hiroki Katagiri, Yacine El Tawil, Niklaus P. Lang, Jean-Claude Imber, Anton Sculean, Masako Fujioka-Kobayashi, Nikola Saulacic
Summary: This study evaluated the influence of additional hydroxyapatite in collagen-based matrices and membrane placement on bone formation in calvarial defects. Results showed that mineralized collagen-based matrices induced more small bony islands in central areas of defects, but complete defect closure was not observed. Membrane placement decreased bone density and height, with significant effects on bone height in the central area, but did not improve osteogenic capacity.
Review
Biochemistry & Molecular Biology
Jana Reiterova, Vladimir Tesar
Summary: Alport syndrome (AS) is a genetic kidney disease caused by mutations in COL4A3, COL4A4, or COL4A5 genes. It is characterized by hematuria, proteinuria, and kidney failure. Current treatment options are limited, but RAS inhibitors and SGLT-2 inhibitors show promise. Ongoing studies are exploring the use of combined receptor inhibitors and lipid-lowering agents. Molecular genetic diagnosis is crucial for prognosis and future therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Wing Sum Chu, Joanne Ng
Summary: rAAV gene therapy has shown promise but faces challenges due to immune responses, solutions involving immunosuppression or modulation are being explored to overcome these issues.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jieyu Qi, Liyan Zhang, Fangzhi Tan, Yang Zhang, Yinyi Zhou, Ziyu Zhang, Hongyang Wang, Chaorong Yu, Lulu Jiang, Jiancheng Liu, Tian Chen, Lianqiu Wu, Shanzhong Zhang, Sijie Sun, Shan Sun, Ling Lu, Qiuju Wang, Renjie Chai
Summary: This study demonstrates the effectiveness and safety of OTOF gene therapy drugs in mice and nonhuman primates. The researchers developed a new strategy to deliver OTOF and successfully restored hearing in mice with profound deafness. The therapy also showed no impact on normal hearing and systemic toxicity in both mice and nonhuman primates.
Review
Biochemistry & Molecular Biology
Piotr Tarach, Anna Janaszewska
Summary: Carriers of genetic material can be viral or non-viral, with non-viral carriers like PAMAM dendrimers showing promise in gene therapy due to their unique physiochemical properties and modification strategies. However, regulatory issues and limitations in clinical translation still need to be addressed for their broad implementation. Further research and improvements are crucial for the development of PAMAM dendrimers as carriers of genetic material in anticancer gene therapies.
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
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
Robert D. Jolly, Stuart A. Hunter, Maurice R. Alley, Barbara M. King, Adeline A. Lau, Paul J. Trim, Marten F. Snel, Kim M. Hemsley
Summary: A free-living Kaka parrot was diagnosed with mucopolysaccharidosis, with typical histopathological and electron microscopic findings. Genetic factors are suspected to be the cause, as the bird came from a small isolated population. A captive breeding program is ongoing with further investigation into carriers of the disorder.
JOURNAL OF WILDLIFE DISEASES
(2021)
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
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
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)