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149 results for

Inborn Error of Small Molecule Metabolism

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121. EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment

: Cobalamin C (Cbl-C) defect is the most common inborn error of cobalamin metabolism causing methylmalonic aciduria and homocystinuria. Cbl-Cdefect is due to impaired activity of MMACHC, a cobalamin trafficking protein, involved in the decyanation of cyanocobalamin as well as in the dealkylation of alkylcobalamins through a glutathione transferase activity. Despite pharmacological treatment with hydroxycobalamin, betaine, folic acid, (and carnitine), long-term outcome in early-onset patients is in most (...) : Cobalamin C defect methylmalonic aciduria with homocystinuria Visual function VEP ERG antioxidant drugs Additional relevant MeSH terms: Layout table for MeSH terms Genetic Diseases, Inborn Homocystinuria Amino Acid Metabolism, Inborn Errors Vitamin B 12 Deficiency Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Hyperhomocysteinemia Metabolism, Inborn Errors Connective Tissue Diseases Metabolic Diseases Vitamin B

2013 Clinical Trials

122. Environmental contaminants perturb fragile protein assemblies and inhibit normal protein function (PubMed)

of 37 preliminary hits were used to confirm the electrophoretic results and to determine the dose-dependence of the perturbation of oligomeric distribution. Seventeen compounds were identified which alter the oligomeric distribution toward the hexamer and also inhibit HsPBGS catalytic activity, including the most potent HsPBGS inhibitor yet characterized (Mutagen X, IC50 = 1.4 μM). PBGS dysfunction is associated with the inborn error of metabolism know as ALAD porphyria and with lead poisoning (...) Environmental contaminants perturb fragile protein assemblies and inhibit normal protein function The molecular mechanisms whereby small molecules that contaminate our environment cause physiological effects are largely unknown, in terms of both targets and mechanisms. The essential human enzyme porphobilinogen synthase (HsPBGS, a.k.a. 5-aminolevulinate dehydratase, ALAD) functions in heme biosynthesis. HsPBGS catalytic activity is regulated allosterically via an equilibrium of inactive

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2013 Current chemical biology

123. Phenylbutyrate Therapy for Maple Syrup Urine Disease

treatment periods. The results will be compared once the study is over. Condition or disease Intervention/treatment Phase Maple Syrup Urine Disease Drug: Phenylbutyrate Drug: Placebo powder Phase 2 Phase 3 Detailed Description: Maple syrup urine disease is a severe inborn error of amino acid metabolism caused by deficiency of the mitochondrial branched-chain alpha-ketoacid dehydrogenase complex (BCKDC) resulting in the accumulation of branched-chain amino acids (BCAA) (isoleucine, leucine, and valine (...) Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Amino Acid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases 4-phenylbutyric acid Antineoplastic Agents

2012 Clinical Trials

124. In Vivo Selection of Transplanted Hepatocytes by Pharmacological Inhibition of Fumarylacetoacetate Hydrolase in Wild-type Mice (PubMed)

In Vivo Selection of Transplanted Hepatocytes by Pharmacological Inhibition of Fumarylacetoacetate Hydrolase in Wild-type Mice Genetic fumarylacetoacetate hydrolase (Fah) deficiency is unique in that healthy gene-corrected hepatocytes have a strong growth advantage and can repopulate the diseased liver. Unfortunately, similar positive selection of gene-corrected cells is absent in most inborn errors of liver metabolism and it is difficult to reach the cell replacement index required (...) for therapeutic benefit. Therefore, methods to transiently create a growth advantage for genetically modified hepatocytes in any genetic background would be advantageous. To mimic the selective pressure of Fah deficiency in normal animals, an efficient in vivo small molecule inhibitor of FAH, 4-[(2-carboxyethyl)-hydroxyphosphinyl]-3-oxobutyrate (CEHPOBA) was developed. Microarray analysis demonstrated that pharmacological inhibition of FAH produced highly similar gene expression changes to genetic deficiency

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2012 Molecular Therapy

125. Biomarker for Hunter Disease

Manifestations Neurologic Manifestations Nervous System Diseases Genetic Diseases, X-Linked Genetic Diseases, Inborn Heredodegenerative Disorders, Nervous System Mucopolysaccharidoses Carbohydrate Metabolism, Inborn Errors Metabolism, Inborn Errors Lysosomal Storage Diseases Mucinoses Connective Tissue Diseases Metabolic Diseases (...) . Secondary Outcome Measures : The Hunter disease specific biomarker candidates finding [ Time Frame: 24 months ] The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng/μl) within a dried blood spot sample will be validated via liquid chromatography multiple reaction-monitoring mass spectrometry (LC/MRM-MS) and compared with a merged control cohort. The statistically best validated molecule will be considered as a disease specific biomarker. Biospecimen Retention

2011 Clinical Trials

126. Biomarker for Gaucher Disease

System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Hypertrophy Pathological Conditions, Anatomical Liver Diseases Digestive System Diseases (...) with Gaucher disease or high-grade suspicion for Gaucher disease Outcome Measures Go to Primary Outcome Measures : Sequencing of the Gaucher disease related gene [ Time Frame: 4 weeks ] Next-Generation Sequencing (NGS) of the GBA gene will be performed. The mutation will be confirmed by Sanger sequencing. Secondary Outcome Measures : The Gaucher disease specific biomarker candidates finding [ Time Frame: 24 months ] The quantitative determination of small molecules (molecular weight 150-700 kD, given as ng

2011 Clinical Trials

127. A Safety and Efficacy Study of DRL-17822, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor, in Patients With Abnormal Cholesterol Levels

Hyperlipoproteinemias Hyperlipoproteinemia Type II Dyslipidemias Lipid Metabolism Disorders Metabolic Diseases Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn (...) in the reduction of cardiovascular risk. Presently only niacin is approved by the FDA for HDL-C elevation and can raise HDL-C levels by 20-30%. However its use can be limited by a high incidence of flushing and, less commonly, by elevation of blood glucose and potential hepatic toxicity. Cholesteryl ester transfer protein (CETP) inhibitors are being explored for their ability to elevate HDL-C. A small molecule CETP inhibitor, torcetrapib, has been demonstrated to elevate HDL-C by 60-100%. However, a large

2011 Clinical Trials

128. Carglumic acid (Carbaglu)

impairment in urea cycle disorders has been shown to correlate with peak levels of ammonia 4 and the duration of hyperammonemic coma. 5 4 Uchino T, et al. Neurodevelopmental outcome of long-term therapy of urea cycle disorders in Japan. J.Inher. Metab. Dis. 1998: 21 (Suppl 1): 151-159 5 Msall M, et al. Neurologic outcome in children with inborn errors of urea synthesis: outcome of urea- cycle enzymopathies. N Engl J Med 1984: 310: 1500-1505 Clinical Review Virginia Elgin, M.D. and Helen Sile, M.D NDA 22 (...) 160 7.1.3 Pooling of Data Across Studies/Clinical Trials to Estimate and Compare Incidence 161 7.2 Adequacy of Safety Assessments 161 7.2.1 Overall Exposure at Appropriate Doses/Durations and Demographics of Target Populations 162 7.2.2 Explorations for Dose Response 165 7.2.3 Special Animal and/or In Vitro Testing 165 7.2.4 Routine Clinical Testing 166 7.2.5 Metabolic, Clearance, and Interaction Workup 166 7.2.6 Evaluation for Potential Adverse Events for Similar Drugs in Drug Class 166 7.3 Major

2010 FDA - Drug Approval Package

129. Overview of Viruses

during the course of human evolution. A few endogenous human retroviruses have remained transcriptionally active and produce functional proteins (eg, the syncytins that contribute to the structure of the human placenta). Some experts speculate that some disorders of uncertain etiology, such as multiple sclerosis, certain autoimmune disorders, and various cancers, may be caused by endogenous retroviruses. Because RNA transcription does not involve the same error-checking mechanisms as DNA (...) transcription, RNA viruses, particularly retroviruses, are particularly prone to mutation. For infection to occur, the virus first attaches to the host cell at one or one of several receptor molecules on the cell surface. The viral DNA or RNA then enters the host cell and separates from the outer cover (uncoating) and replicates inside the host cell in a process that requires specific enzymes. The newly synthesized viral components then assemble into a complete virus particle. The host cell typically dies

2013 Merck Manual (19th Edition)

130. Congenital disorder

Filho DA (2000). . Sante (in French). 10 (2): 117–21. . Kumar, Abbas and Fausto, eds., Robbins and Cotran's Pathologic Basis of Disease, 7th edition , p.473. Chen, J; Gong, X; Chen, P; Luo, K; Zhang, X (16 August 2016). . BMC Pregnancy and Childbirth . 16 : 225. : . . . Simonsen, H (25 November 2002). "[Screening of newborns for inborn errors of metabolism by tandem mass spectrometry]". Ugeskrift for Laeger . 164 (48): 5607–12. . ^ Wilcken, B; Wiley, V (February 2008). "Newborn screening". Pathology (...) . 40 (2): 104–15. : . . Ezgu, F (2016). Inborn Errors of Metabolism . Advances in Clinical Chemistry . 73 . pp. 195–250. : . . . . Nationwide Children's Hospital. 2012-03-19 . Retrieved 2018-04-02 . . World Health Organization . 2009 . Retrieved Nov 11, 2009 . Gittelsohn, A; Milham, S (1964). . American Journal of Public Health and the Nations Health . 54 (2): 286–294. : . . . Fernando, J; Arena, P; Smith, D. W. (1978). "Sex liability to single structural defects". American Journal of Diseases

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2012 Wikipedia

131. Congenital adrenal hyperplasia

, Santiago; González, Héctor Javier; Vázquez-Cantú, Mercedes; Cruz-Camino, Héctor (27 September 2016). "Incidence of Inborn Errors of Metabolism by Expanded Newborn Screening in a Mexican Hospital". Journal of Inborn Errors of Metabolism and Screening . 4 : 232640981666902. : . Aubrey Milunsky; Jeff Milunsky (29 January 2010). . John Wiley and Sons. pp. 600–. . Retrieved 14 June 2010 . Richard D. McAnulty, M. Michele Burnette (2006) , , p.165 ^ Mais, Daniel D. (2008). Quick compendium of clinical (...) -hydroxylase" is visible near the top center. "17α-hydroxylase" and "17,20 lyase" are carried out by a single enzyme). Depending upon which enzyme is unavailable, there is a reduced production of (lower left) or (upper right). This in turn can lead to increased production of other molecules, due to a buildup of precursors. Cortisol deficiency in CAH is usually partial, and not the most serious problem for an affected person. Synthesis of cortisol shares steps with synthesis

2012 Wikipedia

132. AAVRh.10 Administered to Children With Late Infantile Neuronal Ceroid Lipofuscinosis With Uncommon Genotypes or Moderate/Severe Impairment

College of Cornell University: Batten Disease Additional relevant MeSH terms: Layout table for MeSH terms Neuronal Ceroid-Lipofuscinoses Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Nervous System Diseases Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors Lipid Metabolism Disorders Metabolic Diseases (...) . The investigators previous clinical trial used a virus called adeno-associated virus 2 (AAV2) as the gene delivery system. That study showed that viral delivery of the gene was safe and showed small, but significant benefits to the recipient. The investigators currently have an IRB approved protocol which uses a slightly different virus called AAVrh.10 as the gene delivery system. This 3rd protocol proposes to use the same virus AAVrh.10 as the gene delivery system and has expanded the eligibility criteria

2010 Clinical Trials

133. Safety Study of a Gene Transfer Vector (Rh.10) for Children With Late Infantile Neuronal Ceroid Lipofuscinosis

a U.S. FDA-regulated Drug Product: Yes Studies a U.S. FDA-regulated Device Product: No Keywords provided by Weill Medical College of Cornell University: Batten Disease Late Infantile Neuronal Lipofuscinosis gene transfer Additional relevant MeSH terms: Layout table for MeSH terms Neuronal Ceroid-Lipofuscinoses Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Nervous System Diseases Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Metabolism, Inborn Errors (...) with LINCL. The children were assessed by a number of neurological and imaging parameters prior to and after gene transfer. The data demonstrated that the gene transfer was well tolerated and had a small impact on the progression of the disease and suggested that higher doses and a better delivery system may provide greater benefit. The previous study used the viral gene transfer vector adeno-associated virus type 2 (AAV2) at a dose of 2,000,000,000,000 molecules of the drug (2 x 10^12 particle units

2010 Clinical Trials

134. Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita

, 2019 Last Update Posted: February 19, 2019 Last Verified: January 2019 Additional relevant MeSH terms: Layout table for MeSH terms Anemia Fanconi Anemia Fanconi Syndrome Dyskeratosis Congenita Hematologic Diseases Anemia, Hypoplastic, Congenital Anemia, Aplastic Bone Marrow Diseases Genetic Diseases, Inborn DNA Repair-Deficiency Disorders Metabolic Diseases Renal Tubular Transport, Inborn Errors Kidney Diseases Urologic Diseases Metabolism, Inborn Errors Skin Abnormalities Congenital Abnormalities (...) from baseline if baseline platelet count >20,000/ μL. No platelet transfusion during the 4 weeks prior to response evaluation. ANC response: ANC count ≥1,000/ μL if baseline ANC count ≤500/ μL, or ANC count rise >500/ μL from baseline if baseline ANC count >500/ μL. The Gene Expression Profile of Progenitor Cells in Response to Danazol, Both to Predict Responsiveness and to Screen for Small Molecules That Show a Profile Similar to That of Responsive Patients [ Time Frame: Baseline and 24 weeks

2009 Clinical Trials

135. A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease (ENGAGE)

Gaucher Disease Sphingolipidoses Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Eliglustat Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action (...) which have infiltrated the spleen and liver as well as other tissue. Eliglustat tartrate is a small molecule developed as an oral therapy which acts to specifically inhibit production of this storage material in Gaucher cells. This study was designed to determine the efficacy, safety, and pharmacokinetics (PK) of eliglustat tartrate in adult participants (>16 years) with Gaucher disease Type 1. The study consisted of 2 periods: The Double-Blind Primary Analysis Period (PAP [Day 1 to Week 39

2009 Clinical Trials

136. A Study of Eliglustat Tartrate (Genz-112638) in Patients With Gaucher Disease Who Have Reached Therapeutic Goals With Enzyme Replacement Therapy (ENCORE)

Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Eliglustat Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action (...) nervous system (CNS). Typical manifestations of Gaucher disease type 1 include splenomegaly, hepatomegaly, thrombocytopenia, anemia, bone disease, and decreased quality of life. The disease manifestations are caused by the accumulation of glucosylceramide (storage material) in macrophages (called Gaucher cells) which have infiltrated the spleen and liver as well as other tissues. Eliglustat tartrate is a small molecule drug developed as an oral therapy which acts to specifically inhibit production

2009 Clinical Trials

137. Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis

Additional relevant MeSH terms: Layout table for MeSH terms Cystinosis Fanconi Syndrome Lysosomal Storage Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Renal Tubular Transport, Inborn Errors Kidney Diseases Urologic Diseases Cysteamine Cystine Depleting Agents Molecular Mechanisms of Pharmacological Action (...) is dosed every 6 hours and there is no measurement after 6 hours and up to 12 hours. Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline [ Time Frame: up to 12 hours post Cystagon® dosing and RP103 dosing ] The pharmacodynamic (PD) parameter measures the changes of WBC cystine level from the baseline. Cystine is a disulfide amino acid formed through oxidation of two molecules of cysteine; hence, cystine's concentration is commonly given in half-cystine equivalents

2009 Clinical Trials

138. A Phase I Study of Pyrimethamine in Patients With GM2 Gangliosidosis

, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Lipidoses Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders Pyrimethamine Antimalarials Antiprotozoal Agents Antiparasitic Agents Anti-Infective Agents Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action (...) , the lysosomes increase in size and number, giving rise to a storage disease. The majority of the mutations in Hex A affect the ability of the enzyme to obtain and/or retain its native 3-dimensional fold in the endoplasmic reticulum (ER) where intracellular quality control is performed to retain and degrade defective enzymes. Pharmacological chaperones (PC)s are small molecules that can stabilize the native conformation of a mutant enzyme in the ER and allow it to escape the ER's quality control system

2008 Clinical Trials

139. Nutritional and Neurotransmitter Changes in PKU Subjects on BH4

Dihydrochloride Nutrition PHE Phenylalanine PAH Phenylalanine hydroxylase Neurotransmitters Serotonin Catecholamines Diet Body Fat Bone Density Additional relevant MeSH terms: Layout table for MeSH terms Phenylketonurias Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases Nervous System Diseases Amino Acid Metabolism, Inborn Errors Metabolism, Inborn Errors Genetic Diseases, Inborn Metabolic Diseases Verapamil Neurotransmitter Agents Anti-Arrhythmia (...) , since these changes could indicate improved neurological functioning, (5) and quality of life of PKU patients, who may feel less burdened due to the dietary freedom KuvanTM provides. Condition or disease Intervention/treatment Phenylketonuria Drug: KuvanTM Therapy Detailed Description: BACKGROUND : Tetrahydrobiopterin (BH4) is a treatment option newly available to phenylketonuria (PKU) patients within the United States as the pharmaceutical KuvanTM. This small molecule functions as a cofactor

2008 Clinical Trials

140. Anderson-Fabry Disease

and European Guidelines. You may find one of our more useful. In this article In This Article Anderson-Fabry Disease In this article Synonyms: Fabry's disease, alpha-galactosidase A deficiency, hereditary dystopic lipidosis, GLA deficiency Anderson-Fabry disease is an X-linked recessive inborn error of glycosphingolipid metabolism caused by deficiency of alpha-galactosidase A. [ ] It was first described independently in 1898 by Anderson and Fabry but the enzyme deficiency was not defined until the 1960s (...) . The enzyme deficiency leads to defective storage of sphingolipid and progressive endothelial accumulation causing abnormalities in the skin, eye, kidney, heart, brain and peripheral nervous system. The gene responsible for alpha-galactosidase is located on the long arm of the X chromosome. There have been almost 200 mutations identified. Along with it is one of the most prevalent metabolic storage diseases (or lysosomal storage diseases). The gene mutation and enzyme deficiency result in insufficient

2008 Mentor

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