Article
Neurosciences
Thia St Martin, Tania A. Seabrook, Katherine Gall, Jenn Newman, Nancy Avila, April Hayes, Monicah Kivaa, Jason Lotterhand, Michael Mercaldi, Kruti Patel, Israel J. Rivas, Stephen Woodcock, Teresa L. Wright, Albert B. Seymour, Omar L. Francone, Jacinthe Gingras
Summary: This study demonstrates that intravenous administration of HSC15/ARSA can restore the distribution of the corresponding enzyme in patients, and overexpression of ARSA can correct disease biomarkers and improve motor deficits. Compared with intravenously administered AAV9/ARSA, HSC15/ARSA leads to significant increases in brain ARSA activity, transcript levels, and vector genomes. Additionally, the study shows that HSC15/ARSA can cross the blood-nerve, blood-spinal, and blood-brain barriers, and circulating ARSA enzyme activity can be detected in the serum of healthy nonhuman primates.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Daphne H. Schoenmakers, Shanice Beerepoot, Sibren van den Berg, Laura Adang, Annette Bley, Jaap-Jan Boelens, Francesca Fumagalli, Wim G. Goettsch, Sabine Gronborg, Samuel Groeschel, Peter M. van Hasselt, Carla E. M. Hollak, Caroline Lindemans, Fanny Mochel, Peter G. M. Mol, Caroline Sevin, Ayelet Zerem, Ludger Schols, Nicole Wolf
Summary: A group of experts reached consensus on a core set of data elements for a European Metachromatic Leukodystrophy (MLD) registry. The registry will facilitate research, treatment comparisons, and regulatory requirements related to MLD.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Clinical Neurology
Shanice Beerepoot, Hans Heijst, Birthe Roos, Mirjam M. C. Wamelink, Jaap Jan Boelens, Caroline A. Lindemans, Peter M. van Hasselt, Edwin H. Jacobs, Marjo S. van der Knaap, Charlotte E. Teunissen, Nicole Wolf
Summary: This study compared neurofilament light chain and GFAP levels in patients with metachromatic leukodystrophy and healthy controls, suggesting that these two proteins may serve as biomarkers for clinical assessment and treatment decisions.
Article
Endocrinology & Metabolism
Francesca Fumagalli, Alberto A. Zambon, Paola M. V. Rancoita, Cristina Baldoli, Sabrina Canale, Ivana Spiga, Stefania Medaglini, Rachele Penati, Marcella Facchini, Francesca Ciotti, Marina Sarzana, Laura Lorioli, Martina Cesani, Maria Grazia Natali Sora, Ubaldo Del Carro, Federica Cugnata, Gigliola Antonioli, Salvatore Recupero, Valeria Calbi, Clelia Di Serio, Alessandro Aiuti, Alessandra Biffi, Maria Sessa
Summary: This study characterizes the natural course of metachromatic leukodystrophy (MLD) and explores differences between different subgroups. It identifies factors influencing disease progression and highlights differences in disease-related milestones among MLD subtypes. The study also provides insights into reliable clinical and instrumental tools for monitoring disease progression and evaluating therapeutic interventions.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Sifei Wu, Mei Hou, Yu Zhang, Jie Song, Ya Guo, Peipei Liu, Yedan Liu, Liping Yi, Xiaoyu Pan, Wei We, Zongbo Chen
Summary: Metachromatic leukodystrophy is a neurodegenerative disorder caused by mutations in the ARSA gene, leading to deficiency of the ARSA enzyme. Common clinical features include abnormal gait and neurological symptoms. Studying novel ARSA gene mutations can provide further insights into the pathogenesis of Metachromatic leukodystrophy.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Genetics & Heredity
Caroline Sevin, Magalie Barth, Alexandra Wilds, Abena Afriyie, Markus Walz, Annamarie Dillon, Kenneth Howie, Francis Pang
Summary: This multinational study aimed to quantify the impact of MLD on caregivers. The results showed that MLD consistently negatively affects caregivers' lives in various aspects, including health, relationships, and professional status. This study contributes to improving patient care and providing support for individuals with MLD and their families.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Neuroimaging
Joana Feldmann, Pascal Martin, Benjamin Bender, Lucia Laugwitz, Laimdota Zizmare, Christoph Trautwein, Ingeborg Krageloh-Mann, Uwe Klose, Samuel Groeschel
Summary: The study aims to investigate the correlation between MR spectroscopy (MRS) and clinical parameters for motor and cognitive function in patients with metachromatic leukodystrophy (MLD). The results show that MLD spectra differ significantly from controls, with more severe changes in late-infantile patients. N-acetylaspartate (NAA) seems to be the most clinically meaningful biomarker for disease progression in MLD.
NEUROIMAGE-CLINICAL
(2023)
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)
Correction
Clinical Neurology
Chiara Benzoni, Marco Moscatelli, Silvia Fenu, Anna Venerando, Ettore Salsano
Summary: There was a mistake in the original version of the article.
JOURNAL OF NEUROLOGY
(2021)
Article
Clinical Neurology
An I. Jonckheere, Sandra D. K. Kingma, Francois Eyskens, Victoria Bordon, Anna C. Jansen
Summary: Metachromatic leukodystrophy (MLD) is a neurodegenerative disorder caused by gene mutations. Treatment options vary based on age and symptoms at onset, with allo-HSCT being the traditional choice. However, the outcomes are inconsistent and new treatment options are being explored. Newborn screening for MLD is becoming important in the changing therapeutic field.
EUROPEAN JOURNAL OF PAEDIATRIC NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Melissa R. Pergande, Christina Kang, Diann George, Pearl A. Sutter, Stephen J. Crocker, Stephanie M. Cologna, Maria Givogri
Summary: This study investigates the lipid content of brain-derived extracellular vesicles (EVs) in a mouse model of Metachromatic Leukodystrophy. The results suggest age-dependent alterations of sulfatides and their precursors in EVs, providing potential biomarkers for the disease.
LIPIDS IN HEALTH AND DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Nayibe Tatiana Sanchez-Alvarez, Paula Katherine Bautista-Nino, Juanita Trejos-Suarez, Norma Cecilia Serrano-Diaz
Summary: Metachromatic leukodystrophy is a neurological disease that affects public health. This research focuses on the use of metformin as a treatment to counteract the effects of enzyme deficiencies and sulfatide accumulation. The study found that transfected human Schwann cells showed increased cell reactive oxygen species production when exposed to sulfatides, and sulfatides affected mitochondrial bioenergetics in these cells. Treatment with metformin restored the metabolic activity of the cells and decreased ROS production.
Article
Biotechnology & Applied Microbiology
Marena Trinidad, Xinying Hong, Steven Froelich, Jessica Daiker, James Sacco, Hong Phuc Nguyen, Madelynn Campagna, Dean Suhr, Teryn Suhr, Jonathan H. LeBowitz, Michael H. Gelb, Wyatt T. Clark
Summary: By collecting patient data and conducting enzyme activity assays, researchers found that over 1/3 of ARSA gene variants may be pathogenic. They also developed an algorithm to predict the phenotype of MLD patients, providing clinicians with a tool to anticipate disease progression and guide treatment.
Article
Biochemistry & Molecular Biology
Sally Esmail, Wayne R. Danter
Summary: Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disease caused by a deficiency of ARSA enzyme. While there are currently no effective treatments, aiWBO simulations offer a potential to better understand MLD pathogenesis and guide future research.
Review
Biochemistry & Molecular Biology
Chen Li, Wang Jing-Min
Summary: Metachromatic leukodystrophy (MLD) is a rare hereditary leukoencephalopathy caused by ARSA gene mutation. Currently, there is no effective treatment for MLD, but recent studies have shown that intrathecal injection of rhASA can delay disease progression. Prenatal molecular diagnosis is the main method for preventing MLD.
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS
(2022)
