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.
Article
Biotechnology & Applied Microbiology
Marta Pares, Cristina Fornaguera, Ferran Vila-Julia, Sejin Oh, Steven H. Y. Fan, Ying K. Tam, Natalia Comes, Francisco Vidal, Ramon Marti, Salvador Borros, Jordi Barquinero
Summary: This study demonstrated the successful integration of a TYMP transgene into hepatocytes in a murine model of MNGIE using CRISPR/Cas9 and TYMP cDNA. The best in vivo results were obtained with LNP delivering CRISPR/Cas9 mRNA, showing long-term reduction in plasma nucleoside levels. Editing the Tymp and Alb loci resulted in transgene expression and functional enzyme production in liver cells, highlighting the potential of liver-directed genome editing for correcting MNGIE.
HUMAN GENE THERAPY
(2021)
Article
Medicine, Research & Experimental
Marco Peviani, Sabyasachi Das, Janki Patel, Odella Jno-Charles, Rajesh Kumar, Ana Zguro, Tyler D. Mathews, Paolo Cabras, Rita Milazzo, Eleonora Cavalca, Valentina Poletti, Alessandra Biffi
Summary: Hematopoietic stem and progenitor cells (HSPCs) can be used to treat the severe CLN1 neurodegenerative disorder, and the transplantation of HSPCs over-expressing hPPT1 enhances the therapeutic benefit. This novel approach shows promise for treating CLN1 disease and other neurodegenerative conditions.
EMBO MOLECULAR MEDICINE
(2023)
Article
Oncology
Yolanda Aguilera, Nuria Mellado-Damas, Laura Olmedo-Moreno, Victor Lopez, Concepcion Panadero-Moron, Marina Benito, Hugo Guerrero-Cazares, Catalina Marquez-Vega, Alejandro Martin-Montalvo, Vivian Capilla-Gonzalez
Summary: Utilizing mesenchymal stem cells through intranasal application is a safe and non-invasive strategy for treating neurological disorders, as evidenced by studies conducted on mice. The repeated doses of cells administered through the nostrils did not cause any serious adverse events or tumor formation, demonstrating the potential for future clinical trials. These findings support the use of intranasal MSC therapy for managing central nervous system diseases.
Article
Biochemistry & Molecular Biology
Xuewen Song, Wouter N. Leonhard, Anish A. Kanhai, Gregory R. Steinberg, York Pei, Dorien J. M. Peters
Summary: In this study, the combined administration of salsalate and tolvaptan was tested in an adult-onset Pkd1 knock-out mouse model. The combination therapy showed better therapeutic effects compared to individual drugs, improving kidney survival and reducing kidney weight to body weight ratio, cystic index, and blood urea levels. Gene expression and protein phosphorylation analyses supported the mild beneficial effects of co-treatment, showing cooperative attenuation of kidney injury, cell proliferation, inflammation, and fibrosis by tolvaptan and salsalate, as well as improvement in mitochondrial health and cellular antioxidant response.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Sherif G. Ahmed, Casey A. Maguire, Shiliang Alice Cao, Gary J. Brenner
Summary: Schwannomas are tumors derived from Schwann-lineage cells. Currently, treatment options for schwannomas are limited and associated with significant complications. Researchers have successfully reduced tumor volume and pain in experimental models using gene therapy. The safety and efficacy data support the translation of this gene therapy strategy to clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Anastasiia Kalinina, Alexandra Bruter, Nadezhda Persiyantseva, Yulia Silaeva, Maria Zamkova, Ludmila Khromykh, Dmitry Kazansky
Summary: This study evaluated the safety of experimental TCR alpha-modified T cell product in mouse preclinical models, showing no tumorigenic or mutagenic activity in vitro and no toxicity or immunotoxicity in vivo. Pharmacokinetics analysis revealed rapid distribution of modified T cells in various organs with no off-target activity.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Dito Anurogo, Nova Yuli Prasetyo Budi, Mai-Huong Thi Ngo, Yen-Hua Huang, Jeanne Adiwinata Pawitan
Summary: Hereditary anemia presents with various manifestations, and current management strategies are unsatisfactory. Gene-corrected hematopoietic stem cell transplantation may offer promising outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Guelcihan Ozek, Serap Aksoylar, Sema Kalkan Ucar, Ebru Canda, Mediha Akcan, Ozgur Carti, Zuhal Onder Sivis, Yesim Oymak, Havva Yazici, Bridget Bax, Fatma Derya Bulut, Merve Yoldas Celik, Fehime Erdem, Mahmut Coker, Savas Kansoy
Summary: In this retrospective study, the effectiveness of reduced toxicity myeloablative conditioning regimen in hematopoietic stem cell transplantation (HSCT) for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients was evaluated. Results showed that the Treosulfan-based regimen was well tolerated, although engraftment failure is a significant concern.
PEDIATRIC BLOOD & CANCER
(2023)
Review
Cell & Tissue Engineering
Harinad B. Maganti, Adrian J. M. Bailey, Aidan M. Kirkham, Risa Shorr, Nicolas Pineault, David S. Allan
Summary: Gene editing of blood-derived cells shows potential for curing monogenic diseases, but remains experimental. Research indicates that CRISPR/Cas9-edited cells demonstrate similar engraftment as unedited cells, but face challenges in persistence, highlighting the need for improved targeting methods. Significant heterogeneity in study design and potential bias suggest further improvements are necessary for informative clinical trials.
STEM CELLS TRANSLATIONAL MEDICINE
(2021)
Article
Cell & Tissue Engineering
Rashin Mohseni, Pouya Mahdavi Sharif, Maryam Behfar, Mohammad Reza Modaresi, Rohola Shirzadi, Mahta Mardani, Leila Jafari, Fahimeh Jafari, Zeynab Nikfetrat, Amir Ali Hamidieh
Summary: This study aimed to assess the safety and effectiveness of adipose tissue-derived mesenchymal stem cells (AT-MSCs) for pediatric patients with bronchiolitis obliterans syndrome (BoS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The results showed that a single injection of AT-MSCs partially improved the symptoms of patients and the treatment was safe and tolerable.
STEM CELL RESEARCH & THERAPY
(2023)
Review
Clinical Neurology
Shreya N. Kashyap, Nicholas R. Boyle, Erik D. Roberson
Summary: This article reviews the preclinical development of therapies for frontotemporal dementia caused by heterozygous loss-of-function mutations in progranulin (FTD-GRN). The focus is on testing these therapies in mouse models. Approaches to raise progranulin levels, such as increasing expression from the normal allele or facilitating production by the mutant allele, as well as delivering progranulin across the blood-brain barrier or using gene therapy, have been discussed. Several of these approaches have entered clinical trials, offering hope for new therapies for FTD-GRN.
Review
Clinical Neurology
Shreya N. Kashyap, Nicholas R. Boyle, Erik D. Roberson
Summary: This article reviews the preclinical development of therapies for frontotemporal dementia (FTD) caused by heterozygous loss-of-function mutations in the progranulin gene (GRN), with a focus on testing in mouse models. Most FTD-GRN-associated mutations cause progranulin haploinsufficiency, so these therapies aim to raise progranulin levels. Different approaches have been explored, including increasing progranulin expression from the normal allele, facilitating progranulin production by the mutant allele, and delivering progranulin across the blood-brain barrier or through gene therapy. Some of these approaches have entered clinical trials, suggesting potential new treatments for FTD-GRN.
Review
Cell & Tissue Engineering
Chengxin Luo, Li Wang, Guixian Wu, Xiangtao Huang, Yali Zhang, Yanni Ma, Mingling Xie, Yanni Sun, Yarui Huang, Zhen Huang, Qiuyue Song, Hui Li, Yu Hou, Xi Li, Shuangnian Xu, Jieping Chen
Summary: Through network meta-analysis comparing the efficacy of different HSC mobilization regimens, it was found that regimens including G-CSF plus AMD3100, Me6, EP80031, and ML141 showed promising results in terms of collecting CFCs and LSK cells.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Cell Biology
Paula Germino-Watnick, Malikiya Hinds, Anh Le, Rebecca Chu, Xiong Liu, Naoya Uchida
Summary: Autologous hematopoietic stem cell (HSC)-targeted gene therapy provides a one-time cure for various genetic diseases including sickle cell disease (SCD) and beta-thalassemia. This review discusses the methods of gene addition and gene editing in HSC-targeted gene therapy for SCD.
Article
Biochemistry & Molecular Biology
Miguel Molina-Berenguer, Ferran Vila-Julia, Sandra Perez-Ramos, Maria Teresa Salcedo-Allende, Yolanda Camara, Javier Torres-Torronteras, Ramon Marti
Summary: Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1 (COXPD1) is a mitochondrial translation disorder caused by mutations in GFM1. Mouse models with Gfm1 knock-in and knock-out mutations were generated to study COXPD1. The knock-in mice showed normal growth but had decreased mitochondrial EFG1 protein content, while the knock-out mice were embryonically lethal. The compound heterozygous mice had impaired mitochondrial translation and respiratory chain dysfunction, making them suitable for studying COXPD1.
Article
Ophthalmology
S. E. Detiger, G. J. Hotte, R. M. Verdijk, R. O. B. de Keizer, P. M. van Hagen, J. A. M. van Laar, D. Paridaens
Summary: This study describes the clinical behavior, treatment effect, and long-term outcome of a series of patients with adult orbital xanthogranulomatous disease (AOXGD). Different subtypes require different treatment options, with surgical excision potentially suitable for AOX patients, while systemic therapy is warranted for AAPOX, NBX, and ECD patients. There is currently no conclusive evidence for a superior treatment strategy and further research is needed.
Article
Radiology, Nuclear Medicine & Medical Imaging
Adriana A. S. Tavares, Laura Mezzanotte, Wendy McDougald, Monique R. Bernsen, Christian Vanhove, Markus Aswendt, Giovanna D. Ielacqua, Felix Gremse, Carmel M. Moran, Geoff Warnock, Claudia Kuntner, Marc C. Huisman
Summary: This study surveyed and summarized the current status of preclinical imaging standardization through community survey and forum discussions. The results showed that there are still challenges in standardizing preclinical imaging techniques, with significant variations in data acquisition, processing, and reporting, and limited awareness of international guidelines for preclinical (imaging) research practices.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Review
Genetics & Heredity
Irenaeus F. M. de Coo, Sarah Jesse, Thuy-Linh Le, Carlo Sala
Summary: Phelan-McDermid syndrome (PMS) is a 22q13.3 deletion syndrome characterized by developmental disturbances, neurological and psychiatric features, and sometimes comorbidities such as seizures. Different types of seizures can occur in PMS and the use of EEG and MRI is important for diagnosis and determining the need for anticonvulsant therapy. This study focused on the prevalence and semiology of epileptic seizures associated with the SHANK3 gene or 22q13 deletion involving SHANK3 in PMS, in order to provide recommendations for diagnosis and therapy as part of European consensus guidelines.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Daniel P. de Bruyn, Michiel Bongaerts, Ramon Bonte, Jolanda Vaarwater, Magda A. Meester-Smoor, Robert M. Verdijk, Dion Paridaens, Nicole C. Naus, Annelies de Klein, George J. G. Ruijter, Emine Kilic, Erwin Brosens
Summary: Using untargeted metabolomics, we identified differential metabolite patterns in UM patients compared to controls. The random forest classifier and leave-one-out cross-validation confirmed the discriminatory ability of these metabolite patterns in distinguishing UM patients from controls, but not in differentiating high-risk and low-risk UM patients. Dysregulation of metabolite patterns may be associated with processes related to malignancies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Maria Chiara Gelmi, Robert M. Verdijk, Laurien E. Houtzagers, Pieter A. van der Velden, Wilma G. M. Kroes, Gregorius P. M. Luyten, T. H. Khanh Vu, Martine J. Jager
Summary: MITF is an important regulator of melanogenesis and melanocyte development. MITF loss in uveal melanoma is associated with a shift in epithelial-to-mesenchymal transition factors and increased inflammation. Low MITF expression is also related to genetic changes such as monosomy 3/BAP1 loss and 8q gain/amplification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Marianna Bugiani, Truus E. M. Abbink, Arthur W. D. Edridge, Lia van der Hoek, Anne E. J. Hillen, Niek P. van Til, Gino V. Hu-A-Ng, Marjolein Breur, Karen Aiach, Philippe Drevot, Michael Hocquemiller, Ralph Laufer, Frits A. Wijburg, Marjo S. van der Knaap
Summary: The AAVance gene therapy trial investigated the intracerebral injection of AAVrh.10 overexpressing human sulfamidase in children with MPSIIIA. Post-treatment MRI monitoring revealed lesions around injection sites. Investigations showed dysfunction of transduced cells close to the injection sites, leading to altered extracellular matrix composition and cystic white matter degeneration. The potential benefit-risk ratio of this therapy will be revealed by the trial results.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Review
Oncology
Alessia Pellerino, Robert M. Verdijk, Lucia Nichelli, Nicolaus H. Andratschke, Ahmed Idbaih, Roland Goldbrunner
Summary: The 2021 WHO classification of the CNS Tumors recognizes Peripheral nerve sheath tumors (PNST) as a distinct group with specific characteristics and recommends diagnostic and therapeutic approaches based on limited evidence due to their rarity. Diagnosis is mainly determined by histological analysis and immunohistochemistry, with genetic analysis required for mosaic forms of NF1 and SPS. MRI is the preferred method for assessing tumor extent. Complete resection is the preferred treatment, balancing nerve preservation. Radiotherapy can be omitted in benign and NF-related tumors. Systemic therapy is recommended for incompletely resected plexiform neurofibromas/MPNSTs, with MEK inhibitors and anthracycline-based treatment being potential options. Clinical trials on MEK1-2 inhibitors and mTOR inhibitors are underway for plexiform neurofibromas and MPNST, respectively.
Editorial Material
Ophthalmology
Tatyana Milman, Hans E. Grossniklaus, Gabrielle Goldman-Levy, Tero T. Kivela, Sarah E. Coupland, Valerie A. White, Hardeep Singh Mudhar, Charles G. Eberhart, Robert M. Verdijk, Steffen Heegaard, Anthony J. Gill, Martine J. Jager, Aberlardo A. Rodriguez-Reyes, Bita Esmaeli, Jennelle C. Hodge, Ian A. Cree
Summary: The 5th edition of the WHO Classification of Tumours of the Eye and Orbit is a significant step in standardizing diagnostic practices globally. It introduces new chapters and consolidates sections, highlighting recent advances in etiology, pathogenesis, and diagnosis of eye and orbital tumors. This edition also includes updates on classification schemes and newly identified tumors. The editorial summarizes the major changes and specific updates in each taxonomic category, focusing on advances in understanding tumor pathogenesis, diagnostic criteria, and molecular markers.
OCULAR ONCOLOGY AND PATHOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jolique A. van Ipenburg, Quincy C. C. van den Bosch, Dion Paridaens, Hendrikus J. Dubbink, Emine Kilic, Nicole Naus, Robert M. Verdijk, Rotterdam Ocular Melanoma Study Grp
Summary: This study aimed to determine the prognostic value of ATRX loss in conjunctival melanocytic lesions and found that ATRX loss and TERT promoter mutations are only found in (pre)malignant conjunctival melanocytic lesions, with most metastatic cases harboring one of these alterations, suggesting that both alterations are associated with adverse behavior. Similar to TERT promoter mutations, ATRX loss may be used as a diagnostic tool in determining whether a conjunctival melanocytic lesion is prone to having an adverse course.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Luis G. Alcala-Gonzalez, Anna Accarino, Ramon Marti, Daniel Sanchez-Tejerina, Arnau Llaurado, Fernando Azpiroz, Carolina Malagelada
Summary: This study aims to describe gastrointestinal motor dysfunction in MNGIE patients using advanced techniques and evaluate the relationship between motor abnormalities and symptoms. The results show that MNGIE patients have characteristic motor dysfunction in the small bowel, even in the presence of mild digestive symptoms. Early investigation is necessary.
NEUROGASTROENTEROLOGY AND MOTILITY
(2023)
Review
Pharmacology & Pharmacy
Fatima Aerts-Kaya, Niek P. van Til
Summary: Leukodystrophies are a group of genetic degenerative brain disorders that can be lethal if not treated. Gene therapy offers promising results for the treatment of leukodystrophies, and this article discusses the potential interventions of gene therapy in certain types of leukodystrophies, such as X-linked adrenoleukodystrophy and metachromatic leukodystrophy. The advantages and disadvantages of different gene therapy approaches are also discussed, along with the ongoing developments in the field of molecular technologies for treating leukodystrophies in the future.
Article
Ophthalmology
Maria Chiara Gelmi, Annemijn P. A. Wierenga, Wilma G. M. Kroes, Sjoerd G. van Duinen, Jessica S. Karuntu, Marina Marinkovic, Jaco C. Bleeker, Gregorius P. M. Luyten, T. H. Khanh Vu, Robert M. Verdijk, Martine J. Jager
Summary: This study analyzed the association between genetic tumor parameters and tumor pigmentation in uveal melanoma (UM). The results showed that heavily pigmented tumors had worse prognosis compared to nonpigmented tumors, and tumor pigmentation was correlated with chromosome abnormalities and PRAME expression.
OPHTHALMOLOGY SCIENCE
(2023)
Article
Medicine, Research & Experimental
Jonathan Shintaku, Wolfgang M. Pernice, Wafaa Eyaid, B. G. C. Jeevan, Zuben P. Brown, Marti Juanola-Falgarona, Javier Torres-Torronteras, Ewen W. Sommerville, Debby M. E. I. Hellebrekers, Emma L. Blakely, Alan Donaldson, Ingrid van de laar, Cheng-Shiun Leu, Ramon Marti, Joachim Frank, Kurenai Tanji, David A. Koolen, Richard J. Rodenburg, Patrick F. Chinnery, H. J. M. Smeets, Grainne S. Gorman, Penelope E. Bonnen, Robert W. Taylor, Michio Hirano
Summary: This article reports 5 patients from 4 families who presented with ptosis and ophthalmoplegia as well as multiple mtDNA deletions in muscle. The study identifies RRM1 deficiency as a cause of the disease and reveals the disruption of nucleotide synthesis.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
