Review
Medicine, General & Internal
Marcela Junqueira Brunelli, Alvaro N. Atallah, Edina M. K. da Silva
Summary: MPS VI, also known as Maroteaux-Lamy syndrome, is a rare genetic disorder characterized by deficiency of arylsulphatase B, leading to accumulation of dermatan sulphate and lysosomal damage. Clinical manifestations primarily include skeletal dysplasia and various systemic complications. Enzyme replacement therapy with galsulfase is a new approach for treatment, but its effectiveness and safety remain uncertain based on current evidence. Further studies are needed to clarify its long-term effects and potential adverse events.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)
Article
Medicine, Research & Experimental
Elizabeth Hwang-Wong, Gabrielle Amar, Nanditha Das, Xiaoli Zhang, Nina Aaron, Kirsten Gale, Nyanza Rothman, Massimo Fante, Andrew Baik, Ajay Bhargava, Arun Fricker, Michelle Mcalister, Jeremy Rabinowitz, John Lees-Shepard, Kalyan Nannuru, Aris N. Economides, Katherine D. Cygnar
Summary: This study reveals the importance of early intervention in improving skeletal phenotypes in Mucopolysaccharidosis VI (MPS VI). Current enzyme replacement therapy shows limited efficacy in treating the skeletal manifestations of MPS VI.
Review
Biochemistry & Molecular Biology
Joanne K. Tobacman, Sumit Bhattacharyya
Summary: The enzyme ARSB has a broader impact on human pathobiology, acting as a tumor suppressor, transcriptional mediator, redox switch, and regulator of intracellular and extracellular-cell signaling, in addition to its role in Mucopolysaccharidosis VI.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Francesca Maccari, Laura Rigon, Veronica Mantovani, Fabio Galeotti, Marika Salvalaio, Francesca D'Avanzo, Alessandra Zanetti, Federica Capitani, Orazio Gabrielli, Rosella Tomanin, Nicola Volpi
Summary: This study examined the changes in plasma and urinary GAGs in Ids knock-out (Ids-ko) mice over a 24-week follow-up, with and without enzyme replacement therapy (ERT). Untreated Ids-ko mice showed increased levels of GAGs, while ERT was associated with a decrease in heparan-sulfate (HS) and partially in chondroitin-sulfate (CS) and dermatan-sulfate (DS). Various structural parameters were altered in untreated mice and partially restored after ERT, although not reaching physiological levels.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Review
Biochemistry & Molecular Biology
Francesca D'Avanzo, Alessandra Zanetti, Concetta De Filippis, Rosella Tomanin
Summary: Mucopolysaccharidosis type VI, or Maroteaux-Lamy syndrome, is a rare autosomal recessive genetic disease mainly affecting pediatric age group. It is caused by enzyme deficit leading to pathological accumulation starting from the osteoarticular apparatus, emphasizing the need for new disease biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Torayuki Okuyama, Yoshikatsu Eto, Norio Sakai, Kimitoshi Nakamura, Tatsuyoshi Yamamoto, Mariko Yamaoka, Toshiaki Ikeda, Sairei So, Kazunori Tanizawa, Hiroyuki Sonoda, Yuji Sato
Summary: The study demonstrated that pabinafusp alfa is a potentially effective treatment for both the central and peripheral symptoms of MPS-II patients, with the ability to cross the blood-brain barrier to reach the central nervous system. In the 52-week clinical trial, the drug showed relatively good efficacy and safety profiles.
Article
Biotechnology & Applied Microbiology
Roberto Giugliani, Ana Maria Martins, Sairei So, Tatsuyoshi Yamamoto, Mariko Yamaoka, Toshiaki Ikeda, Kazunori Tanizawa, Hiroyuki Sonoda, Mathias Schmidt, Yuji Sato
Summary: The novel drug pabinafusp alpha has shown potential in crossing the blood-brain barrier and addressing neurodegenerative diseases, with favorable clinical outcomes in MPS-II patients.
Article
Endocrinology & Metabolism
Nathalie Guffon, Pratima Chowdary, Elisa Leao Teles, Derralynn Hughes, Julia B. Hennermann, Philippe Huot-Marchand, Elodie Faudot-Vernier, Olivier Lacombe, Anne Fiquet, Marie-Paule Richard, Jean-Louis Abitbol, Mireille Tallandier, Christian J. Hendriksz
Summary: Odiparcil, an orally available small molecule, has shown promising safety and tolerability in MPS VI patients, with improvements in pain, corneal clouding, cardiac, vascular, and respiratory functions. Further evaluation of odiparcil in younger patients is warranted.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Roberto Giugliani, Ana Maria Martins, Torayuki Okuyama, Yoshikatsu Eto, Norio Sakai, Kimitoshi Nakamura, Hideto Morimoto, Kohtaro Minami, Tatsuyoshi Yamamoto, Mariko Yamaoka, Toshiaki Ikeda, Sairei So, Kazunori Tanizawa, Hiroyuki Sonoda, Mathias Schmidt, Yuji Sato
Summary: This article discusses the effectiveness of enzyme replacement therapy on MPS patients and the significant progress in addressing central nervous system symptoms in MPS-II patients with pabinafusp alfa.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Genetics & Heredity
Asli Inci, Ilyas Okur, Leyla Tumer, Gursel Biberoglu, Murat Oktem, Fatih Ezgu
Summary: This study described the clinical manifestations and events of Turkish patients with MPS VI who received ERT, showing improvements in endurance and a decrease in urinary incontinence after 1.9 to 3.2 years of treatment. However, ERT did not prevent the progression of certain complications. Long-term data revealed a shift in the nature of events over time, with a decrease in respiratory tract infections and sleep problems, but an increase in ophthalmologic events, ear tube insertions, and depression.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biochemistry & Molecular Biology
Victor J. Alvarez, Susana B. Bravo, Maria Pilar Chantada-Vazquez, Cristobal Colon, Maria J. De Castro, Montserrat Morales, Isidro Vitoria, Shunji Tomatsu, Francisco J. Otero-Espinar, Maria L. Couce
Summary: MPS IVA is a lysosomal storage disease caused by mutations in the GALNS gene, leading to skeletal dysplasia. Enzyme replacement therapy has shown positive results in improving daily activities, but further research is needed to assess its impact on bone lesions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Isadora Andrade, River Ribeiro, Zumira A. Carneiro, Roberto Giugliani, Catarina Pereira, Claudia Cozma, Daniel Grinberg, Lluisa Vilageliu, Charles M. Lourenco
Summary: Mucopolysaccharidosis VI, or Maroteaux-Lamy disease, is a genetic disease that can be treated with enzyme replacement therapy to slow down disease progression. However, it cannot prevent the occurrence of major symptoms. Enzyme replacement therapy has a positive impact on the patient's survival.
JOURNAL OF MEDICAL CASE REPORTS
(2022)
Article
Medicine, Research & Experimental
Feng Wang, Derek R. Moen, Chelsee Sauni, Shih-hsin Kan, Shan Li, Steven Q. Le, Brett Lomenick, Xiaoyi Zhang, Sean Ekins, Srikanth Singamsetty, Jill Wood, Patricia Dickson, Tsui-Fen Chou
Summary: The study demonstrated a potential therapeutic option for MPS IIID using a proof-of-concept enzyme replacement therapy with recombinant human alpha-N-acetylglucosamine-6-sulfatase (rhGNS) delivered via intracerebroventricular (ICV) route in a neonatal mouse model. The rhGNS treatment showed efficacy in normalizing enzymatic activity, reducing glycosaminoglycan levels, and reversing heparan sulfate accumulation in the brain tissues of MPS IIID mice. This suggests that further development and exploration of rhGNS delivered into CSF as a treatment for MPS IIID is warranted.
MOLECULAR PHARMACEUTICS
(2021)
Article
Endocrinology & Metabolism
Miles C. Smith, Lalitha R. Belur, Andrea D. Karlen, Kelly Podetz-Pedersen, Olivia Erlanson, Kanut Laoharawee, Justin Furcich, Troy C. Lund, Yun You, Davis Seelig, Beau R. Webber, R. Scott McIvor
Summary: A new immunodeficient mouse model of MPS II was developed using CRISPR/Cas9 technology, which exhibited characteristics of MPS II, such as accumulation of GAGs and neurocognitive deficits. This model can be used for evaluating therapeutic approaches for MPS II.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Multidisciplinary Sciences
Kari Pollock, Sabrina Noritake, Denise M. Imai, Gabrielle Pastenkos, Marykate Olson, Whitney Cary, Sheng Yang, Fernando A. Fierro, Jeannine White, Justin Graham, Heather Dahlenburg, Karl Johe, Jan A. Nolta
Summary: A novel immune deficient MPSIIIA mouse model (MPSIIIA-TKO) was created in this study, which exhibits the MPSIIIA disease phenotype and lacks T cells, B cells, and NK cells. This model has the potential to test human cellular therapies in animal models.
SCIENTIFIC REPORTS
(2023)
Article
Genetics & Heredity
Amanda Bingaman, Christine Waggoner, Sara M. Andrews, Diana Pangonis, Marie Trad, Roberto Giugliani, Ruben Giorgino, Jeanine Jarnes, Rojan Vakili, Victoria Ballard, Holly L. Peay
Summary: GM1-gangliosidosis (GM1) is a rare neurodegenerative disorder that leads to early mortality and progressive decline of physical skills and cerebral functioning. This study is the first to explore the priorities of parents of children with pediatric onset forms of GM1. The study identifies the symptoms most critical to caregivers and provides important insights for the development of patient-focused treatments.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Biotechnology & Applied Microbiology
Edina Poletto, Andrew Oliveira Silva, Ricardo Weinlich, Priscila Keiko Matsumoto Martin, Davi Coe Torres, Roberto Giugliani, Guilherme Baldo
Summary: Lysosomal storage disorders (LSD) are rare genetic diseases caused by mutations in lysosomal function-related genes. Gene therapy is a promising approach for LSD due to their monogenic nature and the ability of lysosomal proteins to cross-correct neighboring cells. Ex vivo gene therapy using modified cells from various sources, such as stem cells and hematopoietic precursors, is underway.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2023)
Meeting Abstract
Endocrinology & Metabolism
Paul Harmatz, Roberto Giugliani, Ana M. Martins, Takashi Hamazaki, Ryutaro Kira, Toru Kubo, Yuji Sato, Satoshi Kawashima, Toshiaki Ikeda, Sairei So, Kazunori Tanizawa, Mathias Schmidt
MOLECULAR GENETICS AND METABOLISM
(2023)
Meeting Abstract
Endocrinology & Metabolism
Paul Harmatz, Can H. Ficicioglu, Roberto Giugliani, Deepa Rajan, Joseph Hagood, Michele Fiscella, Lin Yang, Michelle Gilmor, Yoonjin Cho, Dawn Phillips, Paulo Falabella
MOLECULAR GENETICS AND METABOLISM
(2023)
Meeting Abstract
Endocrinology & Metabolism
Joseph Muenzer, Paul Harmatz, Barbara K. Burton, Deepa Rajan, Simon A. Jones, Steven D. Chessler, Natalie Engmann, Adam Scheller, Charlene Chen, Rupa Caprihan, Akhil Bhalla, Tony Hung, Jason Nachtigall, Imanol Zubizarreta, Angela Kay, Simona Costanzo, Jeffrey M. Harris, Yuda Zhu, Peter Chin, Matthew D. Troyer, Carole Ho, Anna I. Bakardjiev
MOLECULAR GENETICS AND METABOLISM
(2023)
Editorial Material
Obstetrics & Gynecology
Jennifer L. Cohen, Pranesh Chakraborty, Karen Fung-Kee-Fung, Marisa E. Schwab, Deeksha Bali, Sarah P. Young, Michael H. Gelb, Hamid Khaledi, Alicia DiBattista, Stacey Smallshaw, Felipe Moretti, Derek Wong, Catherine Lacroix, Dina El Demellawy, Kyle C. Strickland, Jane Lougheed, Anita Moon-Grady, Billie R. Lianoglou, Paul Harmatz, Priya S. Kishnani, Tippi C. MacKenzie
Summary: This study reports on the efficacy of in utero enzyme replacement therapy (ERT) in a patient with CRIM-negative infantile-onset Pompe disease with cardiomyopathy. The results suggest that starting ERT earlier may improve outcomes both prenatally and postnatally, highlighting the need for further research in larger samples.
OBSTETRICAL & GYNECOLOGICAL SURVEY
(2023)
Article
Pharmacology & Pharmacy
Anna-Maria Wiesinger, Brian Bigger, Roberto Giugliani, Christina Lampe, Maurizio Scarpa, Tobias Moser, Christoph Kampmann, Georg Zimmermann, Florian B. Lagler
Summary: Mucopolysaccharidosis (MPS) is a rare group of metabolic diseases with limited treatment options. This study proposes the use of immunomodulatory drugs in innovative individual treatment trials (ITTs) for MPS patients and develops a risk-benefit model for drug evaluation. The decision analysis framework (DAF) includes literature analysis, quantitative risk-benefit assessment, and phenotypic profiling. Four immunomodulatory drugs, adalimumab, abatacept, anakinra, and cladribine, show promise for MPS treatment. This evidence-based model provides a step towards precision medicine in MPS using immunomodulators.
Article
Biochemistry & Molecular Biology
Nuno Lopes, Maria L. Maia, Catia S. Pereira, Ines Mondragao-Rodrigues, Esmeralda Martins, Rosa Ribeiro, Ana Gaspar, Patricio Aguiar, Paula Garcia, Maria Teresa Cardoso, Esmeralda Rodrigues, Elisa Leao-Teles, Roberto Giugliani, Maria F. F. Coutinho, Sandra Alves, M. Fatima Macedo
Summary: In MPS VI disease patients, there is a decrease in the percentage of natural killer cells and monocytes compared to controls. However, there are no alterations in the percentage of T cells, invariant NKT cells, and B cells in both MPS II and VI disease patients. Interestingly, MPS VI disease patients have a higher frequency of naive T cells and lower memory T cell frequency compared to control subjects.
Review
Genetics & Heredity
Matej Mlinaric, James R. Bonham, Viktor Kozich, Stefan Koelker, Ondrej Majek, Tadej Battelino, Ana Drole Torkar, Vanesa Koracin, Dasa Perko, Ziga Iztok Remec, Barbka Repic Lampret, Maurizio Scarpa, Peter C. J. I. Schielen, Rolf H. Zetterstrom, Urh Groselj
Summary: The COVID-19 pandemic had negative impacts on the newborn screening programs, causing missed cases of inherited metabolic diseases due to decreased diagnostic quality. Contingency plans were implemented to address the problems emerged at the start of the pandemic, including staff shortage and modified work schedules. Adaptations and modifications were made in sample collection, resource sharing, and telemedicine utilization to ensure the continuity of the screening programs.
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
(2023)
Correction
Endocrinology & Metabolism
Joseph Muenzer, Barbara K. Burton, Paul Harmatz, Luis Gonzalez-Solana, Matilde Ruiz-Garcia, Simon A. Jones, Nathalie Guffon, Michal Inbar-Feigenberg, Drago Bratkovic, Michael Hale, Yuna Wu, Karen S. Yee, David A. H. Whiteman, David Alexanderian
MOLECULAR GENETICS AND METABOLISM
(2023)
Correction
Endocrinology & Metabolism
Joseph Muenzer, Barbara K. Burton, Paul Harmatz, Luis Gonzalez Gutierrez-Solana, Matilde Ruiz-Garcia, Simon A. Jones, Nathalie Guffon, Michal Inbar-Feigenberg, Drago Bratkovic, Michael Hale, Yuna Wu, Karen S. Yee, David A. H. Whiteman, David Alexanderian
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Genetics & Heredity
Adriana M. Montano, Agnieszka Rozdzynska-Swiatkowska, Agnieszka Jurecka, Antonio Nino Ramirez, Lin Zhang, Deborah Marsden, Raymond Y. Wang, Paul Harmatz
Summary: This study examined growth patterns in patients with mucopolysaccharidosis (MPS) VII before enzyme replacement therapy. The results showed that the height Z-scores of MPS VII patients were near normal until 1 year of age but declined thereafter, especially among males. There was no consistent pattern in weight Z-score. BMI Z-scores were above normal among males and slightly below normal among females.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2023)
Article
Medicine, Research & Experimental
Nicole Muschol, Anja Koehn, Katharina von Cossel, Ilyas Okur, Fatih Ezgu, Paul Harmatz, Maria J. de Castro Lopez, Maria Luz Couce, Shuan-Pei Lin, Spyros Batzios, Maureen Cleary, Martha Solano, Igor Nestrasil, Brian Kaufman, Adam J. Shaywitz, Stephen M. Maricich, Bernice Kuca, Joseph Kovalchin, Eric Zanelli
Summary: This study found that intracerebroventricular administration of tralesinidase alfa can effectively treat Sanfilippo type B and normalize HS and HS-NRE levels in brain tissues. This treatment also reduces hepatomegaly and improves cognitive development in patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Retraction
Pharmacology & Pharmacy
Anna-Maria Wiesinger, Brian Bigger, Roberto Giugliani, Christina Lampe, Maurizio Scarpa, Tobias Moser, Christoph Kampmann, Georg Zimmermann, Florian B. Lagler