Article
Medicine, General & Internal
Elena Martin-Hernandez, Pilar Quijada-Fraile, Patricia Correcher, Silvia Meavilla, Paula Sanchez-Pintos, Javier de las Heras Montero, Javier Blasco-Alonso, Lucy Dougherty, Ana Marquez, Luis Pena-Quintana, Elvira Canedo, Maria Concepcion Garcia-Jimenez, Pedro Juan Moreno Lozano, Mercedes Murray Hurtado, Maria Camprodon Gomez, Delia Barrio-Carreras, Mariela de los Santos, Mireia del Toro, Maria L. Couce, Isidro Vitoria Minana, Montserrat Morales Conejo, Marcello Bellusci
Summary: The study demonstrates the safety and efficacy of directly switching from other nitrogen scavengers to GPB in clinical practice, showing improved metabolic control, reduced hyperammonemic crisis rate, and related adverse effects compared to previous treatments.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Endocrinology & Metabolism
Kevin E. Glinton, Charles G. Minard, Ning Liu, Qin Sun, Sarah H. Elsea, Lindsay C. Burrage, Sandesh C. S. Nagamani
Summary: This study retrospectively analyzed 1255 plasma phenylbutyrate metabolite measurements from 387 individuals and found that 4.15% of samples had abnormally elevated phenylacetate (PAA) levels and 4.30% had abnormally elevated PAA:PAGN ratios. These elevations were more likely to occur in younger individuals and were positively associated with NAPBA dose and negatively associated with plasma glutamine and glycine levels.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Endocrinology & Metabolism
Stephen D. Cederbaum, Jeffrey Edwards, Terrie Kellmeyer, Yvette Peters, Robert D. Steiner
Summary: Urea cycle disorders (UCDs) are rare inherited metabolic diseases caused by a deficiency of enzymes or transporters in the urea cycle. Treatment options include the use of nitrogen-scavenging agents like NaPBA or GPB. ACER-001 is a new formulation of NaPBA designed to mask its bitter taste and is being developed as a treatment for UCDs. Phase 1 studies showed that ACER-001 is bioequivalent to NaPBA powder and has a good taste-masking effect.
MOLECULAR GENETICS AND METABOLISM
(2023)
Article
Endocrinology & Metabolism
Nicola Longo, George A. Diaz, Uta Lichter-Konecki, Andreas Schulze, Michal Inbar-Feigenberg, Robert L. Conway, Allison A. Bannick, Shawn E. McCandless, Roberto Zori, Bryan Hainline, Nicholas Ah Mew, Colleen Canavan, Thomas Vescio, Teresa Kok, Marty H. Porter, Susan A. Berry
Summary: This study confirms the safety and efficacy of GPB in UCD patients aged 0-2 months who cannot be managed by dietary protein restriction and/or amino acid supplementation alone. In this population, GPB undergoes intestinal hydrolysis with no accumulation.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Microbiology
Yijun Zhu, Mohammed Dwidar, Ina Nemet, Jennifer A. Buffa, Naseer Sangwan, Xinmin S. Li, James T. Anderson, Kymberleigh A. Romano, Xiaoming Fu, Masanori Funabashi, Zeneng Wang, Pooja Keranahalli, Shawna Battle, Aaron N. Tittle, Adeline M. Hajjar, Valentin Gogonea, Michael A. Fischbach, Joseph A. DiDonato, Stanley L. Hazen
Summary: Recent studies have shown the critical role of gut microbiota in metabolizing dietary phenylalanine into phenylacetic acid (PAA), which is important for the production of phenylacetylglutamine (PAGln) linked to atherosclerotic cardio-vascular disease (ASCVD). Researchers have identified two different microbial pathways, involving phenylpyruvate:ferre-doxin oxidoreductase (PPFOR) and phenylpyruvate decarboxylase (PPDC), for PAA formation in the gut. The abundance of these pathways is significantly higher in ASCVD patients compared to controls. These findings provide insights into the therapeutic targeting of PAGln formation in vivo.
CELL HOST & MICROBE
(2023)
Article
Endocrinology & Metabolism
Shuhei Osaka, Satoshi Nakano, Tadahaya Mizuno, Yuka Hiraoka, Kei Minowa, Saeko Hirai, Ayumu Mizutani, Yusuke Sabu, Yoshiki Miura, Toshiaki Shimizu, Hiroyuki Kusuhara, Mitsuyoshi Suzuki, Hisamitsu Hayashi
Summary: The study found that preprandial oral administration of NaPB can maximize the systemic exposure of the drug and enhance its potency in consuming plasma glutamine. Pre-breakfast low-dose administration has a similar effect on plasma glutamine availability as post-breakfast high-dose administration, and regardless of the regimen, plasma levels of branched-chain amino acids decrease in a dose-dependent manner.
MOLECULAR GENETICS AND METABOLISM
(2021)
Article
Chemistry, Inorganic & Nuclear
M. Sharath Babu, A. Srivani, B. Srinivasa Rao, Dasari Ayodhya
Summary: In this study, indium-modified heteropoly tungstate catalysts were synthesized to enhance the Lewis acidity. The catalysts were characterized by various techniques, confirming the presence of Keggin ion structure after modification. The modification with indium ions improved the acidity and stability of the catalysts. Pyridine adsorbed FT-IR spectra indicated the presence of Lewis acidic sites associated with indium ions. The catalysts showed different acidity and activity depending on the amount of indium ions. The partially exchanged In0.66TPA catalyst exhibited high glycerol conversion and selectivity to glycerol carbonate. Optimum reaction conditions were determined by investigating various reaction parameters.
INORGANICA CHIMICA ACTA
(2023)
Article
Clinical Neurology
Jasmine A. Fels, Jalia Dash, Kent Leslie, Giovanni Manfredi, Hibiki Kawamata
Summary: This study is the first to explore the molecular effects of AMX0035 in ALS patient-derived cells. It shows that AMX0035 has a greater and distinct impact compared with the individual compounds and provides clues to drug targets and mechanisms of action.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ankita Sharma, Chetna Verma, Samrat Mukhopadhyay, Amlan Gupta, Bhuvanesh Gupta
Summary: This study aimed to develop antimicrobial cotton gauze by dip coating a blend of sodium alginate, glycerol, and tannic acid. The coated gauze showed excellent antimicrobial properties and biocompatibility, making it a promising candidate for use in the healthcare sector.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Health Care Sciences & Services
Gillian Yeowell, Danielle Stephanie Burns, Francis Fatoye
Summary: This study investigated the impact of transitioning to GPB on health-related quality of life in children with UCD. Results showed that GPB reduced medication administration burden, but challenges related to the illness may persist. Practitioners should consider the improved characteristics of GPB when making clinical decisions for UCD patients and their caregivers' health-related quality of life.
JOURNAL OF PATIENT-REPORTED OUTCOMES
(2021)
Article
Endocrinology & Metabolism
Can Ficicioglu, Ning Liu, Qin Sun, Andrea Burdett, Abigail Hata, Marty Porter, V. Reid Sutton
Summary: This study investigated the knowledge and usage of hepatic metabolite testing among US clinicians for the treatment of urea cycle disorders. The survey results showed that test users found the testing helpful for ruling out toxicity, informing dosing decisions, and assessing adherence, but there were also uncertainties and concerns about its use.
MOLECULAR GENETICS AND METABOLISM
(2022)
Article
Medicine, General & Internal
Anna Maria Czarnecka, Marta Obara-Michlewska, Dorota Wesol-Kucharska, Milena Greczan, Magdalena Kaczor, Janusz Ksiazyk, Dariusz Rokicki, Magdalena Zielinska
Summary: From the results, we found that the plasma level of S100B is positively correlated with ammonia level, while the plasma level of 3-NT does not correlate with ammonia concentration. This offers a unique perspective for future identification and monitoring of neurological deficits risk-linked with hyperammonemia episodes in patients with inherited hyperammonemias.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Chaya N. Murali, John R. Barber, Robert McCarter, Anqing Zhang, Natalie Gallant, Kara Simpson, Naghmeh Dorrani, Greta N. Wilkening, Ron D. Hays, Lindsay C. Urea Cycle Disorders Consortium, Lindsay C. Burragea, Sandesh C. S. Nagamani
Summary: Individuals with urea cycle disorders have worse health-related quality of life compared to healthy individuals, phenylketonuria patients, and diabetes patients. Liver transplantation and other clinical variables should be further studied for their impact on quality of life in UCDs.
MOLECULAR GENETICS AND METABOLISM
(2023)
Review
Nutrition & Dietetics
Amaya Belanger-Quintana, Francisco Arrieta Blanco, Delia Barrio-Carreras, Ana Bergua Martinez, Elvira Canedo Villarroya, Maria Teresa Garcia-Silva, Rosa Lama More, Elena Martin-Hernandez, Ana Morais Lopez, Montserrat Morales-Conejo, Consuelo Pedron-Giner, Pilar Quijada-Fraile, Sinziana Stanescu, Mercedes Martinez-Pardo Casanova
Summary: Hyperammonaemia is a metabolic disorder that can cause severe neurological damage and even death. Frequent monitoring, nutritional measures, timely use of medications, and extrarenal clearance measures are crucial for its treatment.
Review
Biochemistry & Molecular Biology
Junichi Fujii, Tsukasa Osaki
Summary: When NOS2 expression is induced in M1-polarized macrophages, large amounts of nitric oxide (center dot NO) are produced, which can lead to both inflammation aggravation and elimination of radical-mediated damage. The reaction of center dot NO with superoxide can be toxic, but it can also terminate radical chain reactions and suppress ferroptosis. center dot NO is involved in metabolic remodeling and regulates the defense systems in M1 macrophages.
Article
Genetics & Heredity
Anjali Aggarwal, Nishitha R. Pillai, Charles J. Billington, Lynn Schema, Susan A. Berry
Summary: This case describes a 20-year-old male with a history of myopathy, multiple episodes of rhabdomyolysis, and lactic acidosis, attributed to a likely pathogenic variant in the FDX2 gene. The patient is the third reported case of FDX2-related rhabdomyolysis, with unique metabolic features observed during episodes of metabolic decompensation.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2022)
Article
Endocrinology & Metabolism
Kimberly A. Kripps, Leighann Sremba, Austin A. Larson, Johan L. K. Van Hove, Hoanh Nguyen, Erica L. Wright, David M. Mirsky, David Watkins, David S. Rosenblatt, David Ketteridge, Susan A. Berry, Shawn E. McCandless, Peter R. Baker
Summary: Methionine synthase deficiency (cblG complementation group) is a rare inborn error of metabolism that can present with a variety of clinical symptoms. Treatment with hydroxocobalamin, betaine, folinic acid, and methionine supplementation has shown improvement in biochemical profiles of affected patients, with more favorable outcomes observed in those treated early in life. Further research is needed to determine the long-term efficacy of treatment for cblG.
JOURNAL OF INHERITED METABOLIC DISEASE
(2022)
Editorial Material
Cell Biology
Eric S. Goetzman, Jerry Vockley
Summary: Posttranslational modifications play a role in the pathology of methylmalonic acidemia and could potentially be treated using an acylation-resistant sirtuin target.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Genetics & Heredity
Kevin Wilhelm, Mathew J. Edick, Susan A. Berry, Michael Hartnett, Amy Brower
Summary: With the increasing availability of publicly available sequencing data, it is crucial for healthcare professionals to understand the impact of genetic variation on diagnosis and patient health outcomes. By analyzing longitudinal health information from newborn screening, unreported genetic variants can be discovered, and the accompanying clinical information can provide insights into the relationship between genotype and phenotype.
FRONTIERS IN GENETICS
(2022)
Article
Pharmacology & Pharmacy
Joyanna Hansen, Radha Ramachandran, Jerry Vockley
Summary: This study investigated the familiarity with gene therapy technologies and educational needs among health care providers (HCPs). The findings showed that most physicians were aware of gene therapy, but dietitians had lower familiarity rates. All HCPs expressed a desire for education on gene therapy advancements, with published literature and congress presentations being the preferred sources of information.
CLINICAL THERAPEUTICS
(2022)
Article
Genetics & Heredity
Amy Brower, Kee Chan, Marc Williams, Susan Berry, Robert Currier, Piero Rinaldo, Michele Caggana, Amy Gaviglio, William Wilcox, Robert Steiner, Ingrid A. Holm, Jennifer Taylor, Joseph J. Orsini, Luca Brunelli, Joanne Adelberg, Olaf Bodamer, Sarah Viall, Curt Scharfe, Melissa Wasserstein, Jin Y. Chen, Maria Escolar, Aaron Goldenberg, Kathryn Swoboda, Can Ficicioglu, Dieter Matern, Rachel Lee, Michael Watson
Summary: Each year, a significant number of newborns are identified with conditions through population-based newborn screening (NBS), and advancements in genomic technologies hold promise to expand NBS. However, the expansion of NBS in the United States is slow and occurs condition by condition and state by state. The Newborn Screening Translational Research Network (NBSTRN) conducted the NBS Expansion Study to identify challenges and propose improvements, and found that the capacity to expand NBS varies across the US with an average adoption time of 9.5 years for a new condition. Four factors delaying and complicating NBS expansion were identified.
FRONTIERS IN GENETICS
(2022)
Editorial Material
Genetics & Heredity
Jerry Vockley, Annemieke Aartsma-Rus, Jennifer L. Cohen, Lex M. Cowsert, R. Rodney Howell, Timothy W. Yu, Melissa P. Wasserstein, Thomas Defay
Summary: Rare genetic disorders affect a certain percentage of newborn babies, and early diagnosis and treatment are challenging. The advancement of whole-genome sequencing (WGS) technology provides the possibility of early diagnosis and opens up new avenues for the treatment of rare genetic disorders. However, there are still several challenges to overcome. This article summarizes the impact of WGS on the diagnosis and treatment of rare genetic disorders.
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2023)
Editorial Material
Genetics & Heredity
Jerry Vockley, Thomas Defay, Aaron J. J. Goldenberg, Amy M. M. Gaviglio
Summary: Traditionally, genetic tests for rare genetic diseases have focused on individual diseases, as have the development of new therapies. However, with over 10,000 rare genetic diseases, this approach is not feasible. Whole exome and genome sequencing have revolutionized the diagnosis of genetic disorders by allowing the rapid testing of all relevant genes in a single test. Newborn screening has also expanded, enabling the identification of diseases in pre-symptomatic infants. Similarly, the ability to develop therapies is rapidly expanding with the use of platform technologies that address multiple diseases.
AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS
(2023)
Editorial Material
Genetics & Heredity
Jerry Vockley, Nicola Brunetti-Pierri, Wendy K. Chung, Angus J. Clarke, Nina Gold, Robert C. Green, Stephen Kagan, Tara Moroz, Christian P. Schaaf, Martin Schulz, Elfride De Baere
GENETICS IN MEDICINE
(2023)
Letter
Genetics & Heredity
Jerry Vockley, Nicola Brunetti-Pierri, Wendy K. Chung, Angus J. Clarke, Nina Gold, Robert C. Green, Stephen Kagan, Tara Moroz, Christian P. Schaaf, Martin Schulz, Elfride De Baere
GENETICS IN MEDICINE
(2023)
Article
Endocrinology & Metabolism
Jerry Vockley, Barbara K. K. Burton, Gerard Berry, Nicola Longo, John Phillips, Amarilis Sanchez-Valle, Kimberly A. A. Chapman, Pranoot Tanpaiboon, Stephanie Grunewald, Elaine Murphy, Xiaoxiao Lu, Syeda Rahman, Kathryn Ray, Bridget Reineking, Laura Pisani, Antonio Nino Ramirez
Summary: Long-chain fatty acid oxidation disorders (LC-FAODs) lead to serious energy metabolism deficiencies. Triheptanoin, a medium chain triglyceride, is effective in treating LC-FAOD patients. A study evaluating the long-term safety and efficacy of triheptanoin showed a significant reduction in major clinical events with triheptanoin treatment. The results confirm the long-term efficacy of triheptanoin for LC-FAOD patients.
JOURNAL OF INHERITED METABOLIC DISEASE
(2023)
Article
Cell Biology
Nicolas Manzke Glanzel, Belisa Parmeggiani, Mateus Grings, Bianca Seminotti, Morgana Brondani, Larissa D. Bobermin, Cesar A. J. Ribeiro, Andre Quincozes-Santos, Jerry Vockley, Guilhian Leipnitz
Summary: Sulfite administration in the rat striatum induces myelin abnormalities, neuroinflammation, and oxidative stress, mimicking the pathophysiology of isolated sulfite oxidase and molybdenum cofactor deficiencies. Post-treatment with the PPAR agonist bezafibrate mitigates these alterations, suggesting its potential as a therapeutic intervention.
Article
Medicine, Research & Experimental
Jordan Kho, Urszula Polak, Ming-Ming Jiang, John D. Odom, Jill V. Hunter, Saima M. Ali, Lindsay C. Burrage, Sandesh C. S. Nagamani, Robia G. Pautler, Hannah P. Thompson, Akihiko Urayama, Zixue Jin, Brendan Lee
Summary: Nitric oxide (NO) is a critical signaling molecule implicated in neurocognitive diseases. Excessive and insufficient NO production have both been linked to pathology. This study investigates the effects of NO on brain endothelial cells and the blood-brain barrier using a model of NO deficiency. The results suggest that ASL-mediated NO synthesis is necessary for maintaining brain microvascular endothelial cell functions and BBB integrity.
Article
Endocrinology & Metabolism
Jerry Vockley, Neal Sondheimer, Marja Puurunen, George A. Diaz, Ilona Ginevic, Dorothy K. Grange, Cary Harding, Hope Northrup, John A. Phillips III, Shawn Searle, Janet A. Thomas, Roberto Zori, William S. Denney, Sharon L. Ernst, Kristina Humphreys, Nicole McWhorter, Caroline Kurtz, Aoife M. Brennan
Summary: The study demonstrates that synthetic biotics can lower plasma phenylalanine levels in patients with phenylketonuria, providing a new approach for treating this inherited disorder of phenylalanine metabolism.
Article
Psychiatry
Lisa A. Pan, Jane C. Naviaux, Lin Wang, Kefeng Li, Jonathan M. Monk, Sai Sachin Lingampelly, Anna Maria Segreti, Kaitlyn Bloom, Jerry Vockley, Mark A. Tarnopolsky, David N. Finegold, David G. Peters, Robert K. Naviaux
Summary: Peripheral blood metabolomics can provide insights into the biology of treatment-refractory major depressive disorder with suicidal ideation, and identify individualized differences for personalized care.
TRANSLATIONAL PSYCHIATRY
(2023)