Article
Allergy
Kye Hwa Lee, Dong Yoon Kang, Hyun Hwa Kim, Yi Jun Kim, Hyo Jung Kim, Ju Han Kim, Eun Young Song, James Yun, Hye-Ryun Kang
Summary: By analyzing pre-stored HLA information of transplant patients, the study found that individuals with high-risk HLA genotypes were more likely to experience type B adverse drug reactions (ADRs) when using certain medications. Utilization of pre-stored HLA data can prevent type B ADRs, including severe cutaneous adverse reactions (SCARs).
CLINICAL AND TRANSLATIONAL ALLERGY
(2022)
Article
Genetics & Heredity
Nicole D. Armstrong, Vinodh Srinivasasainagendra, Lakshmi Manasa S. Chekka, Nam H. K. Nguyen, Noor A. Nahid, Alana C. Jones, Rikki M. Tanner, Bertha A. Hidalgo, Nita A. Limdi, Steven A. Claas, Yan Gong, Caitrin W. McDonough, Rhonda M. Cooper-DeHoff, Julie A. Johnson, Hemant K. Tiwari, Donna K. Arnett, Marguerite R. Irvin
Summary: Hypertension is a major risk factor for cardiovascular disease mortality, and African Americans have the highest prevalence of hypertension. This study identifies genetic variants associated with the efficacy of chlorthalidone and changes in glucose levels in African Americans, which could help prevent adverse cardiovascular events.
Article
Pharmacology & Pharmacy
Amanda C. Camargo, Ursula Matte, Mariana R. Botton
Summary: This study aimed to determine the prevalence of adverse drug reactions (ADRs) related to drugs with pharmacogenetic evidence level 1A in a public hospital in Southern Brazil. The results showed that 18.6% of all notified reactions were caused by drugs with pharmacogenetic evidence level 1A, indicating the potential risk of ADRs in individuals. Genetic information could guide and improve clinical outcomes, reducing ADR incidence and treatment costs.
EXPERT OPINION ON DRUG SAFETY
(2023)
Article
Biochemistry & Molecular Biology
Lucas A. M. Franco, Carlos H. V. Moreira, Lewis F. Buss, Lea C. Oliveira, Roberta C. R. Martins, Erika R. Manuli, Jose A. L. Lindoso, Michael P. Busch, Alexandre C. Pereira, Ester C. Sabino
Summary: Chagas disease is a major social and public health issue in Latin America, with adverse reactions to benznidazole (BZN) treatment potentially genetically determined. Genetic and transcriptomic analyses identified chromosome 16 gene region associations and enriched signaling pathways related to BZN adverse reactions. These findings suggest potential for patient risk stratification before initiating BZN treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medical Laboratory Technology
Angela Siemens, Beth Brooks, S. Rod Rassekh, Annelot J. M. Meijer, Mary M. van den Heuvel-Eibrink, Wei Xu, Catrina M. Loucks, Colin J. D. Ross, Bruce C. Carleton
Summary: This study found a close relationship between cisplatin dose intensity and the risk of ototoxicity in children, and this risk is further increased by the presence of TPMT-risk alleles.
THERAPEUTIC DRUG MONITORING
(2023)
Review
Pharmacology & Pharmacy
Abdelbaset A. Elzagallaai, Bruce C. Carleton, Michael J. Rieder
Summary: Cancer is the leading cause of death in American children older than 1 year of age, but advancements in treatment have significantly improved survival rates. However, chemotherapy still has adverse effects on most survivors.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Article
Chemistry, Medicinal
Henry Tan, Scott M. Reed
Summary: The Metabolovigilance database is a comprehensive repository of pharmaceutical and metabolite information, providing data to users and allowing for sorting and downloading. This tool facilitates the collection of drug and side effect information, as well as sorting and organizing compounds based on their physical properties. It is a valuable resource for studying adverse drug reactions and integrating genomic data for personalized medicine.
MOLECULAR INFORMATICS
(2022)
Review
Pharmacology & Pharmacy
Xin Huang, Biwen Hu, Ling Ye, Tong Li, Li He, Wei Tan, Guoping Yang, Jun-Ping Liu, Chengxian Guo
Summary: Children have their own peculiarities in terms of medication use, and adverse drug reactions in children are partly due to genetic factors. Anti-infective drugs are widely used in children and are an important cause of adverse reactions. Although pharmacogenomic technologies are advancing, there is a lack of pediatric-based studies. This review provides a systematic overview of the pharmacogenomics of anti-infective drugs, exploring the relationship between pharmacogenetic frequencies and the incidence of adverse reactions, which can inform future studies of individualized medication use in children.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2023)
Article
Clinical Neurology
Ciaran Campbell, Mark McCormack, Sonn Patel, Caragh Stapleton, Dheeraj Bobbili, Roland Krause, Chantal Depondt, Graeme J. Sills, Bobby P. Koeleman, Pasquale Striano, Federico Zara, Josemir W. Sander, Holger Lerche, Wolfram S. Kunz, Kari Stefansson, Hreinn Stefansson, Colin P. Doherty, Erin L. Heinzen, Ingrid E. Scheffer, David B. Goldstein, Terence O'Brien, David Cotter, Samuel F. Berkovic, Sanjay M. Sisodiya, Norman Delanty, Gianpiero L. Cavalleri
Summary: This study aimed to determine the contribution of genetic variation to psychiatric and behavioral adverse drug reactions associated with levetiracetam. The results showed that a polygenic burden for schizophrenia is a risk factor for levetiracetam-associated psychotic reaction, but no evidence of an increased burden of rare genetic variants was found.
Review
Pharmacology & Pharmacy
Wan-Chun Chang, Reo Tanoshima, Colin J. D. Ross, Bruce C. Carleton
Summary: The clinical implementation of pharmacogenetic biomarkers is growing as new genetic variants associated with drug outcomes are discovered. Incorporating pharmacogenetic information into healthcare improves drug safety and reduces empiricism in drug selection. However, barriers to the implementation of pharmacogenetic testing remain.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 61, 2021
(2021)
Review
Pharmacology & Pharmacy
M. T. Madhushika, T. P. Weerarathna, P. L. G. C. Liyanage, S. S. Jayasinghe
Summary: Adverse Drug Reactions (ADR) impose a significant burden on the healthcare system of a country. The reporting of ADRs varies worldwide and is evolving over time. A key aspect of ADR monitoring is the detection of uncommon ADRs, with many countries regulating ADR reporting through national bodies and utilizing various methods, while advancements in technology offer the potential for improved ADR reporting systems.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ramon Cacabelos, Vinogran Naidoo, Lola Corzo, Natalia Cacabelos, Juan C. Carril
Summary: Pharmacogenomics plays a crucial role in optimizing drug efficacy and safety in preventing adverse drug reactions, but its application in ADR prevention is hindered by limitations such as lack of education and training, unspecific biomarkers, cost-effectiveness issues, administrative challenges, and insufficient regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pediatrics
Sandip Ray, Anju Seth, Sarita Singh, Garima Sharma, Neha Gaur, Yukti Shah, Praveen Kumar, Jagdish Chandra
Summary: This study aimed to actively monitor adverse drug reactions (ADRs) in HIV-infected children newly initiated on antiretroviral therapy (ART), and assess their impact on ART adherence. The results showed that ADRs were frequent but mostly mild and self-limiting. Gastrointestinal symptoms were the most common ADR, and different treatment regimens were significantly associated with different types of ADRs. Children with immunological suppression were at a higher risk of developing ADRs compared to those without it.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Mathematical & Computational Biology
Seok-Jae Heo, Sohee Jeong, Dagyeom Jung, Inkyung Jung
Summary: This article introduces a tree-based scan statistic method for detecting signals of adverse drug reactions in spontaneous reporting system databases and presents several signal detection statistics for matched case-control data. Through simulation studies and practical applications, the effectiveness and superiority of these methods are validated.
Review
Plant Sciences
Rui Zheng, Yang Sun, Xiaoyu Zhang, Chen Zhao, Pengqian Wang, Shiqi Chen, Zhao Chen, Ruijin Qiu, Aihua Liang, Hongcai Shang
Summary: This comprehensive review examines the clinical features of adverse events (AEs) associated with the combination of XYP and RB. The review analyzes data from randomized controlled trials, cohort studies, case-control studies, case reports, case series, and the National Adverse Drug Reaction Monitoring Information System. The most common AE reported is skin and appendage reactions, with a majority of cases being pseudo-allergic reactions. The study recommends increased awareness of the safety of the XYP-RB combination treatment, especially in children, and the standardization of medication protocols.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ligia Fao, Patricia Coelho, Luis Duarte, Rita Vilaca, Michael R. Hayden, Sandra I. Mota, Ana Cristina Rego
Summary: This study demonstrates that c-Src/Fyn proteins play an important role in controlling mitochondrial function and redox regulation in Huntington's disease (HD). Restoring c-Src/Fyn levels in HD improves mitochondrial morphology and function, reducing the levels of oxidant species and cell death. These findings suggest that c-Src/Fyn could be a potential therapeutic target for HD.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Cell Biology
Shao-Ming Wang, Hsiang-En Wu, Yuko Yasui, Michal Geva, Michael Hayden, Tangui Maurice, Mauro Cozzolino, Tsung-Ping Su
Summary: Autophagy is a crucial cellular process with implications in various diseases. In this study, researchers discovered that the molecular chaperone SIGMAR1 is involved in the transport of TFEB into the nucleus by chaperoning the NP protein POM121, which is responsible for recruiting KPNB1. The disruption of this process in ALS-FTD patients with the C9orf72 subtype leads to impaired autophagy. However, overexpression of SIGMAR1 or POM121, as well as treatment with pridopidine, a SIGMAR1 agonist, can rescue these deficits, suggesting their potential therapeutic use.
Article
Pediatrics
Zulfan Zazuli, Catharina J. P. Op 't Hoog, Susanne J. H. Vijverberg, Rosalinde Masereeuw, Shahrad Rod Rassekh, Mara Medeiros, Rodolfo Rivas-Ruiz, Anke H. van der Zee, Bruce C. Carleton
Summary: This study evaluated the incidence of kidney injury in children who received cisplatin using different definitions. The Alt-AKI criteria detected more cases of nephrotoxicity compared to pRIFLE and KDIGO criteria. pRIFLE was more sensitive at detecting actual kidney injury and patients at risk, while KDIGO was better at detecting clinically significant kidney injury.
PEDIATRIC NEPHROLOGY
(2023)
Article
Pediatrics
Kelly R. McMahon, Asaf Lebel, Shahrad Rod Rassekh, Kirk R. Schultz, Tom D. Blydt-Hansen, Geoffrey D. E. Cuvelier, Cherry Mammen, Maury Pinsk, Bruce C. Carleton, Ross T. Tsuyuki, Colin J. D. Ross, Louis Huynh, Mariya Yordanova, Frederik Crepeau-Hubert, Stella Wang, Ana Palijan, Jasmine Lee, Debbie Boyko, Michael Zappitelli
Summary: This study examines the burden of acute kidney injury (AKI) and kidney outcomes in pediatric patients receiving cisplatin therapy. Severe electrolyte abnormalities were found to be associated with kidney outcomes, highlighting the need for dose optimization and follow-up guidelines in post-cisplatin care.
PEDIATRIC NEPHROLOGY
(2023)
Article
Biology
Pawel Joachimiak, Adam Ciesiolka, Emilia Kozlowska, Pawel M. Switonski, Grzegorz Figura, Agata Ciolak, Grazyna Adamek, Magdalena Surdyka, Zaneta Kalinowska-Poska, Maciej Figiel, Nicholas S. S. Caron, Michael R. R. Hayden, Agnieszka Fiszer
Summary: This study used SNP variants to quantitatively determine the allele-specific expression levels in patient-derived cell lines for spinocerebellar ataxia type 3 (SCA3) and Huntington's disease (HD). They found differences in allele expression levels and developed a reliable and quantitative method using SNP-based droplet digital PCR (ddPCR) to analyze low abundant transcripts. This allele-selective approach provides insights into allele-related mechanisms and can improve understanding of polyglutamine diseases.
Article
Pediatrics
Khalid Taha, Atul Sharma, Kristine Kroeker, Colin Ross, Bruce Carleton, David Wishart, Mara Medeiros, Tom D. D. Blydt-Hansen
Summary: This study aims to develop a novel urine test based on metabolomics to estimate the exposure of mycophenolate in pediatric renal transplantation. The urine samples were analyzed for 133 unique metabolites, and a top 10 urinary metabolite classifier was developed to estimate MPA exposure. The test was validated and showed correlation with allograft inflammation and eGFR ratio.
PEDIATRIC TRANSPLANTATION
(2023)
Article
Medical Laboratory Technology
Angela Siemens, Shahrad Rod Rassekh, Colin J. D. Ross, Bruce C. Carleton
Summary: This study aimed to examine how the pharmacogenetic effects of SLC28A3, UGT1A6, and RARG are modulated by cumulative anthracycline doses in the development of cardiotoxicity. The findings suggest that the SLC28A3 variant provides more significant protection for patients receiving higher anthracycline doses, while the UGT1A6 and RARG risk variants significantly increase the risk of cardiotoxicity at low anthracycline doses.
THERAPEUTIC DRUG MONITORING
(2023)
Article
Physiology
Fanny L. Lemarie, Shaun S. Sanders, Yen Nguyen, Dale D. O. Martin, Michael R. Hayden
Summary: Huntington's disease is a neurodegenerative disorder caused by CAG repeat expansion in the HTT gene. We found that huntingtin protein can be palmitoylated at cysteine 214, and proteolytic cleavage at aspartate 552 leads to myristoylation at glycine 553. Blocking caspase cleavage at aspartate 586 increases myristoylation of huntingtin and promotes the interaction between C-terminal and N-terminal fragments.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Neurosciences
James P. Mackay, Amy I. Smith-Dijak, Ellen T. Koch, Peng Zhang, Evan Fung, Wissam B. Nassrallah, Caodu Buren, Mandi Schmidt, Michael R. Hayden, Lynn A. Raymond
Summary: Miniature neurotransmission is increased in the Huntington disease (HD) model, associated with abnormal endoplasmic reticulum (ER) calcium handling. These abnormalities influence neurotransmission indirectly, without direct ER calcium release into the cytoplasm. However, in cortical cultures and brain slices, there are no significant differences in calcium release between the HD-model neurons and wild-type cells.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Biotechnology & Applied Microbiology
Si-Yue Yu, Tiffany Carlaw, Tyler Thomson, Alexandra Birkenshaw, Genc Basha, Daniel Kurek, Cassie Huang, Jayesh Kulkarni, Lin-Hua Zhang, Colin J. D. Ross
Summary: The development of CRISPR genome editing technology has potential for treating genetic diseases, but delivering genome editors to affected tissues is challenging. In this study, a luminescent ABE (LumA) mouse model was developed, which showed restoration of luciferase activity through A-to-G correction. The model was validated using FDA-approved lipid nanoparticle formulations and demonstrated successful restoration of luciferase activity in treated mice. This model can be used to evaluate the efficacy and safety of genome editors and delivery systems for optimizing genome editing therapeutics.
Article
Clinical Neurology
Borje Darpo, Michal Geva, Georg Ferber, Yigal Paul Goldberg, Andres Cruz-Herranz, Munish Mehra, Richard Kovacs, Michael R. Hayden
Summary: Pridopidine, a selective sigma-1 receptor agonist, shows a favorable cardiac safety profile at the therapeutic dose of 45 mg bid, with no clinically relevant effect on the QT interval.
NEUROLOGY AND THERAPY
(2023)
Article
Oncology
Peng Xia, Jingrui Chen, Yadav Sapkota, Erika N. Scott, Yuening Liu, Melissa M. Hudson, Shahrad R. Rassekh, Bruce C. Carleton, Colin J. D. Ross, Eric J. Chow, Zhaokang Cheng
Summary: This study found that RBL2 is an endogenous CDK2 inhibitor in the heart, which can inhibit FOXO1-mediated pro-apoptotic gene expression. Loss of RBL2 increases sensitivity to DOX-induced cardiotoxicity. These findings suggest that RBL2 could be used as a biomarker to predict the risk of cardiotoxicity before the initiation of anthracycline-based chemotherapy.
JACC: CARDIOONCOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Neel Mehta, Renald Gilbert, Parminder S. Chahal, Maria J. Moreno, Nasha Nassoury, Nathalie Coulombe, Viktoria Lytvyn, Mario Mercier, Dorothy Fatehi, Wendy Lin, Emily M. Harvey, Lin-Hua Zhang, Nazila Nazemi-Moghaddam, Seyyed Mehdy Elahi, Colin J. D. Ross, Danica B. Stanimirovic, Michael R. Hayden
Summary: This study aimed to develop a more efficacious AAV gene therapy vector for the treatment of LPLD. The researchers identified AAV8 pVR59 as a superior vector compared to AAV1 (Glybera), with significantly better therapeutic effects at lower doses. AAV8 pVR59 treatment led to long-term correction of LPLD and improvement in pathology.
HUMAN GENE THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Fabio Duarte, Gabriel Vachey, Nicholas S. Caron, Melanie Sipion, Maria Rey, Anselme L. Perrier, Michael R. Hayden, Nicole Deglon
Summary: Huntington's disease is a fatal neurodegenerative disorder that can be treated by inactivating the mutated HTT gene. One approach to selectively inactivate the mutant allele is by using the CRISPR/Cas9 system to remove the first exon of the mutated HTT. However, the frequency of deletion events is still uncertain.
HUMAN GENE THERAPY
(2023)
Article
Clinical Neurology
Rose Gelineau-Morel, Christopher Smyser, J. Steven Leeder
Summary: The recent focus on improving recognition of dystonia in cerebral palsy (DCP) has highlighted the need for more effective treatments. Current pharmacologic recommendations for DCP are based on anecdotal evidence, with minimal to moderate improvements in dystonia. Precision therapeutics can improve treatment outcomes through predictive biomarker identification, patient stratification, individualized interventions, and monitoring of response.