Article
Biotechnology & Applied Microbiology
Claudia Yaghootfam, Marc Sylvester, Boris Turk, Volkmar Gieselmann, Ulrich Matzner
Summary: In this study, human arylsulfatase A (hASA) was genetically engineered to enhance its activity and transfer across the blood-brain barrier (BBB). The modified enzyme, called SuPerTurbo-ASA, showed significantly increased half-life, activity, and uptake in a mouse model. Compared to wild-type hASA, SuPerTurbo-ASA was more efficient in reducing sulfatide storage in the brain and spinal cord. This research could be a significant advancement in enzyme replacement therapy (ERT) and gene therapy for metachromatic leukodystrophy (MLD).
Article
Clinical Neurology
Lulu Xu, Meixiang Zhong, Yajuan Wang, Zhihong Wang, Jie Song, Jing Zhao, Hongyun Yu, Zhencui Yang, Wenjing Yan, Xueping Zheng
Summary: Metachromatic leukodystrophy (MLD) is an autosomal recessive hereditary disorder characterized by sulfatide accumulation. This study presents a case of an adult patient with MLD initially misdiagnosed as multiple sclerosis. Genetic screening revealed a full deletion of exon 4 and a novel p.P220L mutation in the ARSA gene, which were reported for the first time in MLD, updating the mutation profiles of MLD patients.
FRONTIERS IN NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Aysilu Mullagulova, Alisa Shaimardanova, Valeriya Solovyeva, Yana Mukhamedshina, Daria Chulpanova, Alexander Kostennikov, Shaza Issa, Albert Rizvanov
Summary: Metachromatic leukodystrophy (MLD) is a hereditary neurodegenerative disease caused by deficiencies of the lysosomal enzyme ARSA or the SapB protein. Current treatments are limited, but gene therapy using AAV vectors has shown promise. This study evaluates the safety and efficacy of AAV9-ARSA gene therapy administered intravenously or intrathecally in minipigs, providing insights for optimizing MLD gene therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Michael C. Babcock, Christina R. Mikulka, Bing Wang, Sanjay Chandriani, Sundeep Chandra, Yue Xu, Katherine Webster, Ying Feng, Hemanth R. Nelvagal, Alex Giaramita, Bryan K. Yip, Melanie Lo, Xuntian Jiang, Qi Chao, Josh C. Woloszynek, Yuqiao Shen, Shripad Bhagwat, Mark S. Sands, Brett E. Crawford
Summary: A selective small molecule inhibitor that reduces toxic substance levels in the nervous system has shown potential therapeutic effects in mouse models, but exhibited negative impacts in wild-type mice, indicating the need for further research.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Priyanka Mishra, Alexander Silva, Jay Sharma, Jacqueline Nguyen, Donald P. Pizzo, Denise Hinz, Debashis Sahoo, Stephanie Cherqui
Summary: This study found that transplantation of wild-type hematopoietic stem and progenitor cells (HSPCs) prevented the development of Alzheimer's disease (AD) in mice, reducing microglia activation, memory loss, neurocognitive impairment, and amyloid plaques. It also significantly reduced neuroinflammation. Transcriptomic analysis revealed changes in gene expression associated with disease-associated microglia and neurodegeneration-associated endothelial cells. HSPC transplantation shows promise as a therapeutic approach for AD.
Article
Biochemistry & Molecular Biology
Lilian Juliana Lissner, Leticia Rodrigues, Krista Mineia Wartchow, Ederson Borba, Larissa Daniele Bobermin, Fernanda Urruth Fontella, Fernanda Hansen, Andre Quincozes-Santos, Diogo Onofre Gomes Souza, Carlos-Alberto Goncalves
Summary: This study found that injection of MG in rats led to decreased locomotor activity, anxiolytic effects, and impaired short and long-term memory and spatial memory. It also resulted in decreased hippocampal glutamate uptake, glutamine synthetase activity, and glutathione levels. The findings suggest that MG may contribute to brain dysfunction observed in diabetic patients and shed light on the role of astrocytes in disease and therapeutics.
NEUROCHEMICAL RESEARCH
(2021)
Article
Biotechnology & Applied Microbiology
Jonathan B. Rosenberg, Alvin Chen, Bishnu P. De, Jonathan P. Dyke, Douglas J. Ballon, Sebastien Monette, Rodolfo J. Ricart Arbona, Stephen M. Kaminsky, Ronald G. Crystal, Dolan Sondhi
Summary: This study evaluated the safety of intraparenchymal delivery of AAVrh.10hARSA vector to the white matter of NHPs, showing that low dose treatment had no significant adverse effects, while high dose treatment and high dose control group may lead to localized CNS abnormalities.
HUMAN GENE THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Samantha DeRosa, Monica Salani, Sierra Smith, Madison Sangster, Victoria Miller-Browne, Sarah Wassmer, Ru Xiao, Luk Vandenberghe, Susan Slaugenhaupt, Albert Misko, Yulia Grishchuk
Summary: The research demonstrates that gene therapy can rescue motor function in MLIV mouse models and significantly delay paralysis. Intracerebroventricular administration in mice can significantly improve motor function, myelination, and reduce lysosomal storage load.
HUMAN MOLECULAR GENETICS
(2021)
Article
Multidisciplinary Sciences
Sourav K. Bose, Brandon M. White, Meghana V. Kashyap, Apeksha Dave, Felix R. De Bie, Haiying Li, Kshitiz Singh, Pallavi Menon, Tiankun Wang, Shiva Teerdhala, Vishal Swaminathan, Heather A. Hartman, Sowmya Jayachandran, Prashant Chandrasekaran, Kiran Musunuru, Rajan Jain, David B. Frank, Philip Zoltick, William H. Peranteau
Summary: In utero base editing shows potential in correcting disease-causing mutations before birth, improving survival and alleviating symptoms of diseases like MPSI. This approach highlights the feasibility and efficacy of therapeutic base editing in multiple organs before birth, offering promising treatment options for genetic diseases.
NATURE COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Pierre Isnard, Paul Vergnaud, Serge Garbay, Matthieu Jamme, Maeva Eloudzeri, Alexandre Karras, Dany Anglicheau, Valerie Galantine, Arwa Jalal Eddine, Clement Gosset, Franck Pourcine, Mohammed Zarhrate, Jean-Baptiste Gibier, Elena Rensen, Stefano Pietropaoli, Giovanna Barba-Spaeth, Jean-Paul Duong-Van-Huyen, Thierry J. Molina, Florian Mueller, Christophe Zimmer, Marco Pontoglio, Fabiola Terzi, Marion Rabant
Summary: Acute kidney injury is a significant complication in COVID-19 patients, and it is associated with poor prognosis. The major pathological feature in COVID-19 patients is acute tubular injury. The study showed that SARS-CoV-2 can directly infect renal cells and identified potential therapeutic targets.
Article
Medicine, Research & Experimental
Xiu Jin, Jing Su, Qinyu Zhao, Ruiting Li, Jianlu Xiao, Xiaomei Zhong, Li Song, Yi Liu, Kaiqin She, Hongxin Deng, Yuquan Wei, Yang Yang
Summary: This study engineered a modified IDUA protein by adding a brain-targeting peptide to enable effective crossing of the blood-brain barrier. Liver-directed gene therapy using AAV8 vector was evaluated in a mouse model, resulting in sustained restoration of IDUA activity and normalized levels in the brain. This approach provides a novel strategy for the treatment of MPS I-H and other neurodegenerative LSDs.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Biochemistry & Molecular Biology
Elisabetta Lauretti, Ozlem Dincer, Domenico Pratico
Summary: Studies have shown that changes in the expression levels of specific miRNAs are early events in tauopathies and play a functional role in the pathogenesis of the diseases by impacting several mechanisms involved in the development of the associated neuropathology.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Ruben Weckx, Chloe Goossens, Sarah Derde, Lies Pauwels, Sarah Vander Perre, Greet Van den Berghe, Lies Langouche
Summary: This study investigated the therapeutic efficacy and safety of ketone ester 3HHB in septic mice. Continuous infusion of 3HHB improved muscle force and avoided toxicity, while bolus injections of 3HHB increased severity of illness and mortality.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Roy Chun-Laam Ng, Min Jian, Oscar Ka-Fai Ma, Myriam Bunting, Jason Shing-Cheong Kwan, Guang-Jie Zhou, Krishnamoorthi Senthilkumar, Ashok Iyaswamy, Ping-Kei Chan, Min Li, Kenneth Mei-Yee Leung, Siva-Sundara Kumar Durairajan, Karen Siu-Ling Lam, Leung-Wing Chu, Richard Festenstein, Sookja Kim Chung, Koon-Ho Chan
Summary: The decrease in circulating adiponectin levels is associated with neurodegeneration, neuroinflammation, and Alzheimer's disease pathologies. Increasing adiponectin through treatments like adipoRon can improve neuronal insulin signaling, memory functions, and reduce amyloid levels in Alzheimer's disease models.
MOLECULAR PSYCHIATRY
(2021)
Article
Immunology
Barbara Altendorfer, Michael Stefan Unger, Rodolphe Poupardin, Anna Hoog, Daniela Asslaber, Iris Karina Gratz, Heike Mrowetz, Ariane Benedetti, Diana Marisa Bessa de Sousa, Richard Greil, Alexander Egle, David Gate, Tony Wyss-Coray, Ludwig Aigner
Summary: The infiltration of CD8+ T cells into the brain is a prominent feature in aging and neurodegenerative diseases such as Alzheimer's disease. A study found that brain CD8+ T cells in Alzheimer's disease exhibit similar adaptive immune responses as in other inflammatory diseases of the central nervous system, suggesting potential opportunities for immunotherapy.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Heidi Simonis, Claudia Yaghootfam, Marc Sylvester, Volkmar Gieselmann, Ulrich Matzner
HUMAN MOLECULAR GENETICS
(2019)
Article
Clinical Neurology
Nicole Wolf, Marjolein Breur, Bonnie Plug, Shanice Beerepoot, Aimee S. R. Westerveld, Diane F. van Rappard, Sharon de Vries, Maarten H. P. Kole, Adeline Vanderver, Marjo S. van der Knaap, Caroline A. Lindemans, Peter M. van Hasselt, Jaap J. Boelens, Ulrich Matzner, Volkmar Gieselmann, Marianna Bugiani
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2020)
Article
Biochemistry & Molecular Biology
Debora Kaminski, Claudia Yaghootfam, Frank Matthes, Annika Ressing, Volkmar Gieselmann, Ulrich Matzner
HUMAN MOLECULAR GENETICS
(2020)
Article
Peripheral Vascular Disease
Amra Jujic, Frank Matthes, Lotte Vanherle, Henning Petzka, Marju Orho-Melander, Peter M. Nilsson, Martin Magnusson, Anja Meissner
Summary: The study found an association between plasma S1P and elevated systolic blood pressure, validated in both a mouse model and in humans. Further proteomic analysis revealed multiple S1P associations, some of which were sex-specific. In vitro and in vivo validation showed increased expression of vascular dysfunction and inflammation markers in response to S1P.
Article
Biochemistry & Molecular Biology
Claudia Yaghootfam, Bernd Gehrig, Marc Sylvester, Volkmar Gieselmann, Ulrich Matzner
Summary: Research has shown that cells deficient in ASA express an endo-N-deacylase that can hydrolyze sulfatide, with FAAH playing a critical role in this process. Deletion of FAAH from mouse models can lower levels of lyso-sulfatide, but paradoxically exacerbates the disease phenotype in MLD mice.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Franziska E. Uhl, Lotte Vanherle, Frank Matthes, Anja Meissner
Summary: Changes in S1P signaling and CFTR expression are associated with heart failure and target organ damage. CFTR alterations during HF affect systemic and tissue-specific S1P concentrations. The CFTR-S1P axis plays an important role in HF-mediated systemic and pulmonary inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Isabel Goncalves, Loureen Oduor, Frank Matthes, Narjess Rakem, Jakob Meryn, Nikolaos-Taxiarchis Skenteris, Anders Aspberg, Marju Orho-Melander, Jan Nilsson, Ljubica Matic, Andreas Edsfeldt, Jiangming Sun, Eva Bengtsson
Summary: This study found that the expression of osteomodulin in human atherosclerotic plaques is associated with plaque calcification and plaque stability.
Article
Cardiac & Cardiovascular Systems
Dania Al-Sharify, Signe Holm Nielsen, Frank Matthes, Christoffer Tengryd, Jiangming Sun, Federica Genovese, Morten A. Karsdal, Jan Nilsson, Isabel Goncalves, Andreas Edsfeldt
Summary: This study investigated the association of cleaved osteoglycin with plaque phenotype and found that higher levels of cleaved osteoglycin were associated with a stable plaque phenotype and lower risk for future cardiovascular events. This association may be due to reduced cell apoptosis and the ability to retain LDL. Targeting the cleavage of osteoglycin may be a potential therapeutic strategy to stabilize plaques.
Article
Medicine, Research & Experimental
Lotte Vanherle, Frank Matthes, Franziska E. Uhl, Anja Meissner
Summary: CFTR dysfunction is associated with various conditions, including myocardial infarction. Therapeutic increase of CFTR expression can attenuate the associated effects. The effects of potentiating CFTR function post-MI are still unknown.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Clinical Neurology
Murtadha Al-Saady, Shanice Beerepoot, Bonnie C. Plug, Marjolein Breur, Hristina Galabova, Petra J. W. Pouwels, Jaap-Jan Boelens, Caroline Lindemans, Peter M. van Hasselt, Ulrich Matzner, Adeline Vanderver, Marianna Bugiani, Marjo S. van Der Knaap, Nicole I. Wolf
Summary: Patients with stable white matter pathology may experience deterioration in gray matter after hematopoietic stem cell transplantation, leading to cognitive and motor decline. MRI reveals gray matter atrophy, and histological data show absence of donor cells in gray matter structures. These findings suggest that transplantation may not sufficiently address the gray matter component of metachromatic leukodystrophy.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Claudia Yaghootfam, Marc Sylvester, Boris Turk, Volkmar Gieselmann, Ulrich Matzner
Summary: In this study, human arylsulfatase A (hASA) was genetically engineered to enhance its activity and transfer across the blood-brain barrier (BBB). The modified enzyme, called SuPerTurbo-ASA, showed significantly increased half-life, activity, and uptake in a mouse model. Compared to wild-type hASA, SuPerTurbo-ASA was more efficient in reducing sulfatide storage in the brain and spinal cord. This research could be a significant advancement in enzyme replacement therapy (ERT) and gene therapy for metachromatic leukodystrophy (MLD).
Article
Biochemistry & Molecular Biology
Cecilia Skoug, Hueseyin Erdogan, Lotte Vanherle, Joao P. P. Vieira, Frank Matthes, Lena Eliasson, Anja Meissner, Joao M. N. Duarte
Summary: S1P signaling is altered in synapses of insulin resistance and diet-induced obesity models, suggesting a role in T2D-associated synaptic dysfunction.
NEUROCHEMICAL RESEARCH
(2023)
Article
Geriatrics & Gerontology
Nicholas Don-Doncow, Lotte Vanherle, Frank Matthes, Sine Kragh Petersen, Hana Matuskova, Sara Rattik, Anetta Hartlova, Anja Meissner
Summary: Chronic hypercholesterolemia is associated with immune system activation and pro-inflammatory cell infiltration in the brain, leading to memory dysfunction in elderly mice. Therapeutic cholesterol-lowering with simvastatin can reduce inflammation and memory deficits in these mice, while blood pressure-lowering therapy alone may not be as effective in mitigating memory decline.
NPJ AGING AND MECHANISMS OF DISEASE
(2021)
Article
Cardiac & Cardiovascular Systems
Darcy Lidington, Jessica C. Fares, Franziska E. Uhl, Danny D. Dinh, Jeffrey T. Kroetsch, Meghan Sauv, Firhan A. Malik, Frank Matthes, Lotte Vanherle, Arman Adel, Abdul Momen, Hangjun Zhang, Roozbeh Aschar-Sobbi, Warren D. Foltz, Hoyee Wan, Manabu Sumiyoshi, R. Loch Macdonald, Mansoor Husain, Peter H. Backx, Scott P. Heximer, Anja Meissner, Steffen-Sebastian Bolz
JACC-BASIC TO TRANSLATIONAL SCIENCE
(2019)