Article
Medicine, General & Internal
Bartlomiej Pawlik, Urszula Smyczynska, Szymon Grabia, Wojciech Fendler, Izabela Drozdz, Katarzyna Babol-Pokora, Katarzyna Kotulska, Sergiusz Jozwiak, Julita Borkowska, Wojciech Mlynarski, Joanna Trelinska
Summary: This study aimed to analyze the serum miRNA profiles in patients with tuberous sclerosis (TSC) treated with sirolimus, and compare them with those previously treated with everolimus. The results showed significant differences in miRNA expression before and after sirolimus treatment. Some miRNAs were dysregulated in the same directions compared with the everolimus group. Pathway analysis indicated the involvement of the Ras and MAPK signaling pathway. The upregulation of specific miRNAs was associated with the downregulation of the mTOR pathway.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
Krzysztof Sadowski, Kamil Sijko, Dorota Domanska-Pakiela, Julita Borkowska, Dariusz Chmielewski, Agata Ulatowska, Sergiusz Jozwiak, Katarzyna Kotulska
Summary: Rapamycin can be used to treat drug-resistant epilepsy in children with TSC, and can effectively reduce the frequency of seizures at a certain dosage. The combination with vigabatrin has better efficacy.
FRONTIERS IN NEUROLOGY
(2022)
Article
Pediatrics
Shuo Dun, Yang-Yang Wang, Lin Wan, Qiu-Hong Wang, Qian Lu, Xiao-Yan Yang, Qi Zhang, Hui-Min Chen, Lu-Peng Qiu, Li-Ping Zou
Summary: This study investigated the efficacy and safety of sirolimus in children with TSC-associated RAML. It was found that sirolimus could promote the disappearance of TSC-related RAML, and the disappearance rate was correlated with the maximum diameter at baseline, with smaller tumors having a higher disappearance rate.
WORLD JOURNAL OF PEDIATRICS
(2023)
Article
Clinical Neurology
Sameer C. Dhamne, Meera E. Modi, Audrey Gray, Simone Bonazzi, Lucas Craig, Elizabeth Bainbridge, Lahin Lalani, Chloe E. Super, Samantha Schaeffer, Ketthsy Capre, Danuta Lubicka, Guiqing Liang, Doug Burdette, Stephanie M. McTighe, Sarika Gurnani, Sheryl Anne D. Vermudez, Daniel Curtis, Christopher J. Wilson, Mustafa Q. Hameed, Angelica D'Amore, Alexander Rotenberg, Mustafa Sahin
Summary: This study tested the efficacy of a novel mTOR catalytic inhibitor (TC1) in the treatment of TSC and found that it reduced seizure burden, extended survival, and restored normal weight gain in Tsc2 hypomorphic mice. Therefore, TC1 shows promise as a therapeutic option for TSC.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Review
Clinical Neurology
Eleonora Aronica, Nicola Specchio, Mark J. Luinenburg, Paolo Curatolo
Summary: Epileptogenesis in infants with tuberous sclerosis complex (TSC) is a gradual and dynamic process, and several mechanisms, including mTOR dysregulation and GABAergic dysfunction, contribute to this process. Antiseizure medications and drugs targeting the mTOR pathway have been effective in treating TSC-associated epilepsy. Early administration of GABAergic drug vigabatrin delays seizure onset, while mTOR inhibitor everolimus reduces seizure frequency. Further trials are needed to optimize the use of everolimus and evaluate other potential antiseizure drugs. Understanding the complex mechanisms of TSC-related epileptogenesis is crucial for prevention and treatment.
Article
Clinical Neurology
Christine Chin-jung Hsieh, Yu-Chun Lo, Ssu-Ju Li, Ting-Chun Lin, Ching-Wen Chang, Ting-Chieh Chen, Shih-Hung Yang, Yi-Chao Lee, You-Yin Chen
Summary: Tuberous sclerosis complex is a rare hereditary disease characterized by neuropsychiatric symptoms, with limited effectiveness of current pharmacological treatments. Curcumin may help improve learning and memory deficits, while DTI is a sensitive tool for monitoring neuropathological changes.
Article
Medicine, General & Internal
Giorgia Sforza, Gabriele Monte, Alessandra Voci, Lorenzo Figa Talamanca, Laura Papetti, Michela Ada Noris Ferilli, Martina Proietti Checchi, Massimiliano Valeriani, Romina Moavero
Summary: This article presents a case study of a 10-year-old boy who was diagnosed with radiologically isolated syndrome (RIS) after being diagnosed with tuberous sclerosis complex (TSC). It is the third reported case of the co-occurrence of TSC and demyelinating disease, suggesting a potential link between the two conditions.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Clara Bernardelli, Eloisa Chiaramonte, Silvia Ancona, Silvia M. Sirchia, Amilcare Cerri, Elena Lesma
Summary: Cutaneous lesions are a characteristic feature of tuberous sclerosis complex (TSC), a genetic disease with hyperactivated mTOR signaling. Current treatments for TSC cutaneous lesions lack long-term efficacy, and novel pharmacological approaches are needed. This study demonstrates that chromatin remodeling agents, such as 5-azacytidine, may be effective in treating TSC lesions caused by epigenetic events. Additionally, the study reveals the metastatic capability of TSC cells, providing a valuable mouse model for studying disease progression and testing potential treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Mary Dusing, Candi L. LaSarge, Angela White, Lilian G. Jerow, Christina Gross, Steve C. Danzer
Summary: Hyperactivation of the mTOR signaling pathway is associated with various neurologic diseases, while the effects on brain vasculature differ depending on the loss of specific mTOR negative regulators. Loss of Pten or Tsc2 in mouse models leads to altered vessel characteristics, but the extent and nature of the changes vary. Pten loss results in increased vessel length and volume in specific brain regions, while Tsc2 loss causes localized increase in vessel density.
Review
Behavioral Sciences
Romina Moavero, Angelika Muhlebner, Mark Jasper Luinenburg, Dana Craiu, Eleonora Aronica, Paolo Curatolo
Summary: Tuberous sclerosis complex (TSC) is a genetic disease that affects multiple organs and systems, with a high risk of early onset and refractory seizures. The overactivation of the mammalian Target of Rapamycin (mTOR) complex is the main cause of TSC-related manifestations. mTOR inhibitors such as rapamycin and everolimus have shown potential in suppressing seizures and preventing epilepsy development in animal models. Everolimus has been approved for the treatment of refractory seizures associated with TSC, with better efficacy in younger children. Early suppression of abnormal mTOR signaling with mTOR inhibitors may be a more effective approach in treating TSC-related epilepsy.
EPILEPSY & BEHAVIOR
(2022)
Article
Medicine, General & Internal
Dominika Smialek, Sergiusz Jozwiak, Katarzyna Kotulska
Summary: This study is the first to determine and assess the severity of adverse effects of sirolimus administered to children under two years of age with TSC. The study found that adverse effects associated with sirolimus use were frequent yet not life- or health-threatening. Further multicenter prospective clinical trials should determine the long-term safety of sirolimus.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Karen Agricola, Gabrielle Stires, Darcy A. Krueger, Jamie K. Capal, David N. Franz, David M. Ritter
Summary: The long-term use of mTOR inhibitors in TSC patients may increase the risk of developing diabetes, as shown in the analysis of 8 patients who developed diabetes. Early detection is crucial for diabetes management. More studies are needed to investigate the causal relationship, but clinicians should be aware of this potential association when initiating and monitoring treatment.
PEDIATRIC NEUROLOGY
(2021)
Article
Cell Biology
Kleanthi Chalkiadaki, Elpida Statoulla, Maria Zafeiri, Nabila Haji, Jean-Claude Lacaille, Craig M. Powell, Seyed Mehdi Jafarnejad, Arkady Khoutorsky, Christos G. Gkogkas
Summary: Inhibition of Nlgn1 expression in TSC mouse models can rescue cognitive and social behavior deficits without affecting mTORC1 hyperactivation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Ann-Sofie De Meulemeester, Lise Heylen, Aleksandra Siekierska, James D. Mills, Alessia Romagnolo, Nicole N. van der Wel, Eleonora Aronica, Peter A. M. de Witte
Summary: TSC is a genetic disorder caused by mutations in TSC1 and TSC2 genes. A double mutant zebrafish model was used to study the disease, and it was found that the double mutants had a more severe phenotype and could be rescued by rapamycin. The transcriptome of the double mutant zebrafish larvae strongly overlapped with human SEGA lesions.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Larissa Brussa Reis, Eduardo C. Filippi-Chiela, Patricia Ashton-Prolla, Fernanda Visioli, Clevia Rosset
Summary: Tuberous sclerosis complex is a genetic disorder characterized by the development of hamartomas in multiple organs, with potential treatments including mTORC1 inhibitors. Autophagy plays a paradoxical role in TSC, serving as an alternative therapeutic strategy.
GENETICS AND MOLECULAR BIOLOGY
(2021)
Article
Clinical Neurology
Marina Cattaneo, Pierre Jesus, Andrea Lizio, Philippe Fayemendy, Nicoletta Guanziroli, Ettore Corradi, Valeria Sansone, Letizia Leocani, Massimo Filippi, Nilo Riva, Philippe Corcia, Philippe Couratier, Christian Lunetta
Summary: The study revealed that 10% of ALS patients have hypometabolic state, while 40% have hypermetabolic state. Hypometabolism is associated with later need for gastrostomy, non-invasive ventilation and tracheostomy, and hypometabolic patients with ALS have significantly longer survival compared to normometabolic and hypermetabolic patients.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Review
Neurosciences
Edoardo Agosti, Simona Serioli, Kanwaljeet Garg, Alberto Pietrantoni, Pietro Luigi Poliani, Marco Maria Fontanella
Summary: This study reported a rare case of multiple vertebral metastases from anal squamous cell carcinoma (SCC) and aimed to define a treatment strategy. Through case presentation and literature review, it was found that there is currently no universally accepted treatment strategy for vertebral metastases from anal SCC. Prompt and aggressive, local and systemic, and multimodal treatment of the vertebral lesions may be crucial for improving patient outcomes.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2023)
Article
Clinical Neurology
Alberto Pietrantoni, Simona Serioli, Manuela Cominelli, Giovanni Lodoli, Roberto Stefini, Vincenzo Villanacci, Pietro Luigi Poliani
Summary: This article reports a rare case in which a patient was diagnosed with granulomatous hypophysitis, PitNET, and Crohn's disease, providing new evidence for the association between these diseases.
Article
Biochemistry & Molecular Biology
Shoutang Wang, Raki Sudan, Vincent Peng, Yingyue Zhou, Siling Du, Carla M. Yuede, Tingting Lei, Jinchao Hou, Zhangying Cai, Marina Cella, Khai Nguyen, Pietro L. Poliani, Wandy L. Beatty, Yun Chen, Siyan Cao, Kent Lin, Cecilia Rodrigues, Ali H. Ellebedy, Susan Gilfillan, Gordon D. Brown, David M. Holtzman, Simone Brioschi, Marco Colonna
Summary: Genetic studies have shown that microglia play a crucial role in Alzheimer's disease (AD). Microglia that attach to Ab plaques have a transcriptional signature called disease-associated microglia (DAM), which mainly comes from the TREM2-DAP12 receptor complex that signals through the protein tyrosine kinase SYK. The human TREM2R47H variant, associated with a high risk of AD, fails to activate microglia via SYK.
Article
Biochemistry & Molecular Biology
Daniela Coltrini, Adwaid Manu Krishna Chandran, Mirella Belleri, Pietro L. Poliani, Manuela Cominelli, Francesca Pagani, Miriam Capra, Stefano Calza, Simona Prioni, Laura Mauri, Alessandro Prinetti, Julia K. Kofler, Maria L. Escolar, Marco Presta
Summary: This study provides the first evidence that PTX3 is produced in the CNS of GALC-deficient Krabbe patients and twitcher mice. PTX3 may exert a protective role by reducing the neuroinflammatory response that occurs in the spinal cord of GALC-deficient animals.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Valentina Pieri, Alberto L. Gallotti, Denise Drago, Manuela Cominelli, Ilaria Pagano, Valentina Conti, Silvia Valtorta, Angela Coliva, Sara Lago, Daniela Michelatti, Luca Massimino, Federica Ungaro, Laura Perani, Antonello Spinelli, Antonella Castellano, Andrea Falini, Alessio Zippo, Pietro L. Poliani, Rosa Maria Moresco, Annapaola Andolfo, Rossella Galli
Summary: Glioblastoma (GBM), a deadly brain tumor, has dysregulated metabolism that can be targeted for precise therapeutic strategies. Studying GBM sphere-forming cells, researchers identified the L-fucose pathway as a vulnerability specific to mesenchymal GBM, offering a potential precision medicine approach for targeting cancer metabolism.
Article
Genetics & Heredity
Mara Giacche, Alessandra Panarotto, Luigi Mori, Pietro Luigi Poliani, Roberto Lanzi, Marco Schiavo Lena, Maurizio Castellano
Summary: ARMC5 gene genetic screening in 10 patients with PBMAH identified four germline variants, including one known variant and two novel variants. Somatic analysis further supported the pathogenic effect of the germline variants. This study highlights the importance of genetic testing in sporadic PBMAH patients and expands the spectrum of molecular variants involved in PBMAH syndrome.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2023)
Article
Neurosciences
Roberto Liserre, Francesca Branzoli, Francesca Pagani, Magdalena Gryzik, Manuela Cominelli, Evelina Miele, Malgorzata Marjanska, Francesco Doglietto, Pietro Luigi Poliani
Summary: Medulloblastoma (MB) is a common malignant brain tumor in children and rarely found in adults. MB can be classified into four major molecular groups based on transcriptome profile. DNA methylation profiling has identified additional subgroups within these groups. This case report presents a rare occurrence of an adult MB with both non-canonical somatic IDH1(p.R132C) mutation and a GNAS mutation. Further genetic characterization of MB and the use of advanced medical imaging are important for understanding their biology and improving patient management. The findings raise the need for further investigations on therapeutic implications and prognostic relevance.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Sofia Nasini, Sara Tidei, Atea Shkodra, Danilo De Gregorio, Marco Cambiaghi, Stefano Comai
Summary: The synthesis of melatonin decreases with age. While high dose treatment with melatonin has shown anxiolytic, hypnotic, and analgesic effects, little is known about its efficacy in different age groups. This study investigated the effects of melatonin on anxiety-like behavior and the mPFC-dHippo circuit in adolescent and adult mice. The results showed age-dependent differences in the effects of melatonin and its modulation of the mPFC-dHippo circuit, emphasizing the importance of considering age in the study of the pharmacology of melatonin.
Article
Health Care Sciences & Services
Francesca Pagani, Magdalena Gryzik, Elena Somenza, Manuela Cominelli, Piera Balzarini, Alberto Schreiber, Davide Mattavelli, Piero Nicolai, Francesco Doglietto, Pietro Luigi Poliani
Summary: Chordomas are rare primary malignant tumors arising from the notochord, with a propensity for the skull base and sacrococcygeal region. Different histotypes and molecular alterations, including PTEN deficiency, contribute to the aggressiveness of chordomas. PTEN loss leads to hyperactivation of the Akt/mTOR pathway, which promotes cell proliferation and invasiveness. In this study, a new human PTEN-deleted chordoma cell line was established and characterized, exhibiting molecular features similar to the parent tumor. These cells were sensitive to treatment with mTOR inhibitors, suggesting their potential therapeutic value for PTEN-deleted chordoma patients.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Serena Calamaio, Marialaura Serzanti, Jennifer Boniotti, Annamaria Fra, Emirena Garrafa, Manuela Cominelli, Rosanna Verardi, Pietro Luigi Poliani, Silvia Dotti, Riccardo Villa, Giovanna Mazzoleni, Patrizia Dell'Era, Nathalie Steimberg
Summary: The process of developing a new drug is time-consuming and expensive, and hepatotoxicity is a major concern. Animal models have limitations due to interspecies differences, but human induced pluripotent stem cells (hiPSCs) offer new possibilities for drug testing. We miniaturized the process of generating hepatic organoids using hiPSC-derived mesenchymal stem cells, hepatocytes, and endothelial cells. These organoids were cultivated in vitro using static and dynamic cultures, and could be maintained for up to 1 week. This hiPSC-derived liver organoid model could potentially replace animal testing in pharmacological and toxicological studies.
Article
Clinical Neurology
Giancarlo Comi, Letizia Leocani, Luigi Ferini-Strambi, Marta Radaelli, Gloria D. Costa, Roberta Lanzillo, Giacomo Lus, Valentina Bianchi, Sebastiano Traccis, Fioravante Capone, Luigi M. E. Grimaldi, Giuseppe Salemi, Alessandra Cardillo, Valentina Zipoli
Summary: This multicentre observational study evaluated the effects of treatment with oral dimethyl fumarate on the quality of sleep in patients with relapsing-remitting multiple sclerosis. The results showed significant improvement in the quality of sleep and depression symptoms in patients treated with dimethyl fumarate. However, further randomised clinical trials are needed to confirm the long-term treatment benefits.
MULTIPLE SCLEROSIS JOURNAL-EXPERIMENTAL TRANSLATIONAL AND CLINICAL
(2023)
Article
Health Care Sciences & Services
Andrea Tacchino, Michela Ponzio, Paolo Confalonieri, Letizia Leocani, Matilde Inglese, Diego Centonze, Eleonora Cocco, Paolo Gallo, Damiano Paolicelli, Marco Rovaris, Loredana Sabattini, Gioacchino Tedeschi, Luca Prosperini, Francesco Patti, Placido Bramanti, Elisabetta Pedrazzoli, Mario Alberto Battaglia, Giampaolo Brichetto
Summary: This paper describes the design, development, and usability testing of MS Fitness Intervention Training (MS-FIT), a Kinect-based tool implementing customized Pilates exercises for people with MS. The user-centered design approach was used to create an accessible and challenging tool for balance training. The usability testing showed that MS-FIT is a promising system for enhancing the motivation and engagement of people with MS in performing exercises.
JMIR SERIOUS GAMES
(2023)
Article
Ophthalmology
Valerio Castoldi, Gianpaolo Zerbini, Silvia Maestroni, Ilaria Vigano, Paolo Rama, Letizia Leocani
Summary: This study investigates the effects of topical NGF on neuroretina function and shows that NGF can improve retinal functionality and restore retinal structure in Akita mice.
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Medicine, Research & Experimental
Cristina Rivellini, Emanuela Porrello, Giorgia Dina, Simona Mrakic-Sposta, Alessandra Vezzoli, Marco Bacigaluppi, Giorgia Serena Gullotta, Linda Chaabane, Letizia Leocani, Silvia Marenna, Emanuela Colombo, Cinthia Farina, Jia Newcombe, Klaus-Armin Nave, Ruggero Pardi, Angelo Quattrini, Stefano C. Previtali
Summary: Oligodendrocytes are the primary target of demyelinating disorders. Lack of CSN5 (JAB1) expression leads to cellular senescence, chronic inflammation, and oxidative stress, resulting in CNS demyelination, neuroinflammation, and neurodegeneration.
JOURNAL OF CLINICAL INVESTIGATION
(2022)