Article
Biochemistry & Molecular Biology
Janine A. Gilkes, Benjamin L. Judkins, Brontie N. Herrera, Ronald J. Mandel, Sanford L. Boye, Shannon E. Boye, Arun Srivastava, Coy D. Heldermon
Summary: The study evaluated two intracranially administered adeno-associated virus serotype 8 variants for potential treatment of MPS IIIB, with one variant (double Y-F + T-V) showing better efficacy. The IC6 method resulted in the widest biodistribution within the brain, indicating enhanced utility of the capsid modified AAV8 variant for therapeutic purposes.
Review
Biochemistry & Molecular Biology
Marta Kaczor-Kaminska, Kamil Kaminski, Maria Wrobel
Summary: Mucopolysaccharidosis type IIIB is a rare disease caused by mutations in the N-alpha-acetylglucosaminidase gene, resulting in reduced or absent enzyme activity. The disorder is characterized by the accumulation of heparan sulfate in lysosomes. This study reveals that the degradation of heparan sulfate produces monosaccharides and inorganic sulfate, which disrupts the metabolism of L-cysteine and leads to elevated levels of L-cysteine and reduced antioxidant potential in cells.
Article
Clinical Neurology
Shiwei Huang, Zachary J. Beatty, Alexander M. Mckinney, David R. Nascene
Summary: This study aimed to evaluate the apparent pituitary gland enlargement in patients with Sanfilippo syndrome observed at our institution. Twelve patients with Sanfilippo syndrome underwent brain MRI, and the pituitary volumes were estimated using the prolate ellipsoid volume calculation method. The results showed that pituitary volumes in the Sanfilippo cohort were significantly greater than those in the control cohorts. The clinical significance of these morphological changes remains unclear.
Article
Pediatrics
Ilyas Okur, Fatih Ezgu, Roberto Giugliani, Nicole Muschol, Anja Koehn, Hernan Amartino, Paul Harmatz, Maria J. de Castro Lopez, Maria Luz Couce, Shuan-Pei Lin, Spyros Batzios, Maureen Cleary, Martha Solano, Heidi Peters, Joy Lee, Igor Nestrasil, Adam J. Shaywitz, Stephen M. Maricich, Bernice Kuca, Joseph Kovalchin, Eric Zanelli
Summary: This study characterized the longitudinal natural history of disease progression in pediatric subjects with MPS IIIB. The majority of subjects achieved peak cognitive and adaptive behavior scores between ages 3 and 6, followed by a decline in cognitive function and cortical gray matter loss. Most subjects had elevated levels of HS and HS-NRE in cerebrospinal fluid and plasma. The findings suggest that MPS IIIB follows a predictable trajectory in terms of cognitive decline and gray matter atrophy.
JOURNAL OF PEDIATRICS
(2022)
Article
Multidisciplinary Sciences
Ralitsa Petrova, Abhijeet R. Patil, Vivian Trinh, Kathryn E. Mcelroy, Minoti Bhakta, Jason Tien, David S. Wilson, Liling Warren, Jennifer R. Stratton
Summary: This study systematically characterized a classical mouse model of Mucopolysaccharidosis type IIIB (MPS IIIB) through a series of experiments, exploring the disease pathology, biomarkers, and providing an important resource to the scientific community.
SCIENTIFIC REPORTS
(2023)
Review
Psychology, Developmental
Kimberly A. Schreck, Lindsay M. Knapp
Summary: This manuscript provides guidance for clinicians on distinguishing MPS-IIIA from ASD and offers insights into symptoms and clinical interventions.
REVIEW JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2023)
Article
Pharmacology & Pharmacy
N. Matthew Ellinwood, Bethann N. Valentine, Andrew S. Hess, Jackie K. Jens, Elizabeth M. Snella, Maryam Jamil, Shannon J. Hostetter, Nicholas D. Jeffery, Jodi D. Smith, Suzanne T. Millman, Rebecca L. Parsons, Mark T. Butt, Sundeep Chandra, Martin T. Egeland, Ana B. Assis, Hemanth R. Nelvagal, Jonathan D. Cooper, Igor Nestrasil, Bryon A. Mueller, Rene Labounek, Amy Paulson, Heather Prill, Xiao Ying Liu, Huiyu Zhou, Roger Lawrence, Brett E. Crawford, Anita Grover, Ganesh Cherala, Andrew C. Melton, Anu Cherukuri, Brian R. Vuillemenot, Jill C. M. Wait, Charles A. O'Neill, Jason Pinkstaff, Joseph Kovalchin, Eric Zanelli, Emma McCullagh
Summary: This study assessed the long-term tolerability, pharmacology, and clinical efficacy of TA in a canine model of MPS IIIB. The results showed that TA could prevent or limit the biochemical, pathological, and cognitive manifestations of the disease.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
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
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
Chemistry, Multidisciplinary
Sha Zhu, Yerri Jagadeesh, Anh Tuan Tran, Shuki Imaeda, Alisdair Boraston, Dominic S. Alonzi, Ana Poveda, Yongmin Zhang, Jerome Desire, Julie Charollais-Thoenig, Stephane Demotz, Atsushi Kato, Terry D. Butters, Jesus Jimenez-Barbero, Matthieu Sollogoub, Yves Bleriot
Summary: In the study, a pharmacological chaperone approach was explored to enhance the activity of NAGLU in patient fibroblasts affected by Mucopolysaccharidosis type IIIB. By synthesizing a library of iminosugar C-glycosides, it was found that a non-functionalized and wrongly configured beta-homoiminosugar acted as the most promising pharmacological chaperone, promoting a 2.4 fold activity enhancement of mutant NAGLU at its optimal concentration.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Paulina Anikiej-Wiczenbach, Arkadiusz Manski, Katarzyna Milska-Musa, Monika Limanowka, Jolanta Wierzba, Aleksander Jamsheer, Zuzanna Cyske, Lidia Gaffke, Karolina Pierzynowska, Grzegorz Wegrzyn
Summary: This article describes a case of two siblings with highly diverse phenotypes of Mucopolysaccharidosis type IIIB (MPS IIIB), despite carrying the same mutations. Whole exome sequencing analysis revealed an additional mutation in one allele of the AUTS2 gene in the younger patient. The study suggests that the observed differences in phenotype may be attributed to the potentially pathogenic AUTS2 variant.
JOURNAL OF APPLIED GENETICS
(2022)
Article
Endocrinology & Metabolism
Nicolas J. Abreu, Bhavani Selvaraj, Kristen Truxal, Melissa Moore-Clingenpeel, Nicholas A. Zumberge, Kelly A. McNally, Kim L. McBride, Mai-Lan Ho, Kevin M. Flanigan
Summary: The study aimed to quantify changes in segmented brain volumes over 12 months in children with MPS IIIA and IIIB, revealing differences in cerebral white matter, cerebellar cortex, and cerebellar white matter volumes in MPS III patients. Individuals younger than 8 years showed more significant reductions in cerebral cortex and subcortical gray matter. Greater cerebral cortex volume was associated with motor functioning, while greater subcortical gray matter volume was associated with nonverbal functioning.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Pathology
Tyler A. Harm, Shannon J. Hostetter, Ariel S. Nenninger, Bethann N. Valentine, N. Matthew Ellinwood, Jodi D. Smith
Summary: MPS IIIB is a neuropathic lysosomal storage disease characterized by deficient lysosomal enzyme activity. Dogs serve as a replicative model for studying neurologic lesions associated with MPS IIIB, showing pathological and neuroinflammatory changes in the affected spinal cord and dorsal root ganglion.
VETERINARY PATHOLOGY
(2021)
Article
Genetics & Heredity
Agnieszka Rozdzynska-Swiatkowska, Anna Zielinska, Anna Tylki-Szymanska
Summary: This study summarizes over 30 years of observations on growth dynamics in patients with different types of MPS. The results show that growth patterns significantly deviate from the general population, with MPS IVA patients having the most severe growth impairments and MPS III patients having the mildest impairments.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Courtney J. Rouse, Kimberley Hawkins, Nadia Kabbej, Justin Dalugdug, Aishwarya Kunta, Mi-Jung Kim, Shinichi Someya, Zachary Herbst, Michael Gelb, Isabella Dinelli, Elizabeth Butterworth, Darin J. Falk, Erinn Rosenkrantz, Hamza Elmohd, Hamid Khaledi, Samar Mowafy, Frederick Ashby, Coy D. Heldermon
Summary: Mucopolysaccharidosis type IIIB (MPS IIIB) is a lysosomal storage disease caused by gene mutations that result in defective NAGLU protein. The study demonstrates the potential of AAV8 for gene delivery in the treatment of MPS IIIB, with improved expression and distribution compared to other AAV serotypes. The administration of AAVtcm8-coNAGLU leads to correction of lifespan, auditory deficits, increased CNS NAGLU activity, and reduced lysosomal storage levels in the mouse model of MPS IIIB.
HUMAN MOLECULAR GENETICS
(2023)
Article
Neurosciences
Vania Carmona-Alcocer, John H. Abel, Tao C. Sun, Linda R. Petzold, Francis J. Doyle, Carrie L. Simms, Erik D. Herzog
JOURNAL OF NEUROSCIENCE
(2018)
Article
Neurosciences
Jeff R. Jones, Tatiana Simon, Lorenzo Lones, Erik D. Herzog
JOURNAL OF NEUROSCIENCE
(2018)
Article
Oncology
Walter O'Dell, Cristiane Takita, Katherine Casey-Sawicki, Karen Daily, Coy D. Heldermon, Paul Okunieff
Meeting Abstract
Endocrinology & Metabolism
Paul Harmatz, Heather A. Lau, Coy Heldermon, Nancy Leslie, Cheryl Wong Po Foo, Sagar A. Vaidya, Chester B. Whitley
MOLECULAR GENETICS AND METABOLISM
(2019)
Article
Biochemistry & Molecular Biology
Mengxiong Wang, Renan B. Ferreira, Mary E. Law, Bradley J. Davis, Elham Yaaghubi, Amanda F. Ghilardi, Abhisheak Sharma, Bonnie A. Avery, Edgardo Rodriguez, Chi-Wu Chiang, Satya Narayan, Coy D. Heldermon, Ronald K. Castellano, Brian K. Law
Article
Biochemistry & Molecular Biology
Mam Y. Mboge, Zhijuan Chen, Daniel Khokhar, Alyssa Wolff, Lingbao Ai, Coy D. Heldermon, Murat Bozdag, Fabrizio Carta, Claudiu T. Supuran, Kevin D. Brown, Robert McKenna, Christopher J. Frost, Susan C. Frost
BIOCHEMICAL JOURNAL
(2019)
Article
Biology
Cristina Mazuski, Samantha P. Chen, Erik D. Herzog
JOURNAL OF BIOLOGICAL RHYTHMS
(2020)
Article
Biochemistry & Molecular Biology
Janine A. Gilkes, Benjamin L. Judkins, Brontie N. Herrera, Ronald J. Mandel, Sanford L. Boye, Shannon E. Boye, Arun Srivastava, Coy D. Heldermon
Summary: The study evaluated two intracranially administered adeno-associated virus serotype 8 variants for potential treatment of MPS IIIB, with one variant (double Y-F + T-V) showing better efficacy. The IC6 method resulted in the widest biodistribution within the brain, indicating enhanced utility of the capsid modified AAV8 variant for therapeutic purposes.
Article
Multidisciplinary Sciences
Jeff R. Jones, Sneha Chaturvedi, Daniel Granados-Fuentes, Erik D. Herzog
Summary: The daily release of corticosterone depends on coordinated clock gene and neuronal activity rhythms in both suprachiasmatic nucleus vasoactive intestinal peptide (SCNVIP) and paraventricular nucleus corticotropin-releasing hormone (PVNCRH) neurons. The signals from the central circadian pacemaker, the suprachiasmatic nucleus (SCN), are decoded to generate daily rhythms in hormone release through an SCN- PVN circuit. Loss of the clock gene Bmal1 in CRH neurons results in arrhythmic PVNCRH calcium activity and dramatically reduces the amplitude and precision of daily corticosterone release.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Lara Pferdehirt, Anna R. Damato, Michal Dudek, Qing-Jun Meng, Erik D. Herzog, Farshid Guilak
Summary: The circadian clock is crucial for tissue homeostasis, especially in articular cartilage. Disruptions in the circadian clock during inflammation contribute to the development of diseases. Researchers have used synthetic biology and tissue engineering to develop genetically engineered cartilage that can preserve the circadian clock and have anti-inflammatory properties.
Editorial Material
Infectious Diseases
Graeme A. Fenton, Grant Banfill, Kriti Gera, Robert P. Seifert, Coy D. Heldermon
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2023)
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
Physiology
Tracey O. Hermanstyne, Nien-Du Yang, Daniel Granados-Fuentes, Xiaofan Li, Rebecca L. Mellor, Timothy Jegla, Erik D. Herzog, Jeanne M. Nerbonne
Summary: Considerable evidence suggests that subthreshold potassium (K+) channels play a regulatory role in the day-night rhythms of neurons in the suprachiasmatic nucleus (SCN). This study identifies Kv12.1 and Kv12.2-encoded K+ channels as important regulators of the daily oscillations in the firing rates of SCN neurons.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Biology
H. Craig Heller, Erik Herzog, Allison Brager, Gina Poe, Ravi Allada, Frank Scheer, Mary Carskadon, Horacio O. de la Iglesia, Rockelle Jang, Ashley Montero, Kenneth Wright, Philippe Mouraine, Matthew P. Walker, Namni Goel, John Hogenesch, Russell N. Van Gelder, Lance Kriegsfeld, Cheri Mah, Christopher Colwell, Jamie Zeitzer, Michael Grandner, Chandra L. Jackson, J. Roxanne Prichard, Steve A. Kay, Ketema Paul
Summary: Collegiate athletes face various pressures, including academic obligations, performance impact, health issues, and extensive travel. East-west travel disrupts circadian rhythms and affects sleep quality and health. To address these concerns, we provide suggestions and steps such as bedtime protocols, afternoon naps, and adherence to lighting exposure protocols, and encourage collaboration between athletic departments and experts to promote the health and wellbeing of athletes and staff.
JOURNAL OF BIOLOGICAL RHYTHMS
(2023)
Article
Medical Laboratory Technology
Hoda Safari Yazd, Sina Feizbakhsh Bazargani, Christine A. Vanbeek, Kelli King-Morris, Coy Heldermon, Mark S. Segal, William L. Clapp, Timothy J. Garrett
Summary: This study evaluated lipidomic signatures in renal biopsies to understand variations in Fabry disease markers for potential future diagnostic tests. Results indicated a decline in alpha-GAL A enzyme activity in a patient suspected of having non-classical Fabry disease, based on higher levels of Ga2-related lipid biomarker in renal tissue biopsy compared to controls. Lipidomics analysis is shown to be a valuable tool for diagnosing rare disorders, using leftover tissue samples without disrupting normal patient care.
JOURNAL OF MASS SPECTROMETRY AND ADVANCES IN THE CLINICAL LAB
(2021)