Andrew P. Levy
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View article: Rescue of Iqsec2 Knockout Mice with Human IQSEC2 Adeno-Associated Virus Mediated Gene Therapy
Rescue of Iqsec2 Knockout Mice with Human IQSEC2 Adeno-Associated Virus Mediated Gene Therapy Open
The IQSEC2 protein is a guanine nucleotide exchange factor for Arf6. Pathogenic variants in the X-linked IQSEC2 gene are associated with drug-resistant epilepsy, severe intellectual disability, and autism. The vast majority of disease-caus…
View article: Relationship between time-varying achieved HbA<sub>1c</sub> and risk of coronary artery disease events among common haptoglobin phenotype groups with type 2 diabetes: the ADVANCE study
Relationship between time-varying achieved HbA<sub>1c</sub> and risk of coronary artery disease events among common haptoglobin phenotype groups with type 2 diabetes: the ADVANCE study Open
Introduction This study sought to determine whether the association between attaining specific glycated hemoglobin (HbA 1c ) targets (<7.0% (<53 mmol/mol) and ≥8.0% (≥64 mmol/mol) compared with 7.0%–7.9%) over time and risk of incident cor…
View article: Structural and Functional Analysis of the Human IQSEC2 S1474Qfs*133 Mutation
Structural and Functional Analysis of the Human IQSEC2 S1474Qfs*133 Mutation Open
IQSEC2 is a guanine nucleotide exchange factor that modulates synaptic transmission, the excitatory/inhibitor balance and memory consolidation. Pathogenic mutations in the IQSEC2 gene result in epilepsy, cognitive dysfunction and autism sp…
View article: Does the relationship between time-varying achieved HbA1c and risk of coronary events depend on haptoglobin phenotype within the Action for Health in Diabetes (Look AHEAD) study?
Does the relationship between time-varying achieved HbA1c and risk of coronary events depend on haptoglobin phenotype within the Action for Health in Diabetes (Look AHEAD) study? Open
Background Our previous research has identified the haptoglobin (Hp) phenotype as a potential biomarker that could be used to personalize glycemic control in type 2 diabetes mellitus (T2DM) to prevent coronary artery disease (CAD), the mos…
View article: Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type two diabetes: The Veterans Affairs Diabetes Trial
Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type two diabetes: The Veterans Affairs Diabetes Trial Open
The effect of intensive glycemic therapy on CAD events was not dependent on Hp phenotype in the VADT study of veterans with severe diabetes who may represent a population where Hp phenotype information would not be useful for personalizing…
View article: Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study
Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study Open
OBJECTIVE Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants withou…
View article: Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type 2 diabetes: the ADVANCE study
Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type 2 diabetes: the ADVANCE study Open
Objective: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype, but not in participa…
View article: Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type 2 diabetes: the ADVANCE study
Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type 2 diabetes: the ADVANCE study Open
Objective: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype, but not in participa…
View article: Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study
Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study Open
Background Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown w…
View article: Relationship Between Time‐Varying Achieved High‐Density Lipoprotein Cholesterol and Risk of Coronary Events Depends on Haptoglobin Phenotype Within the ACCORD Lipid Study
Relationship Between Time‐Varying Achieved High‐Density Lipoprotein Cholesterol and Risk of Coronary Events Depends on Haptoglobin Phenotype Within the ACCORD Lipid Study Open
Background The Hp (haptoglobin)2‐2 phenotype (~40% of people) is associated with dysfunctional high‐density lipoprotein (HDL) that is heavily oxidized in hyperglycemia, which may explain why raising HDL‐cholesterol (HDL‐C) does not reliabl…
View article: The relationship between time-varying achieved HbA1c and risk of coronary events depends on haptoglobin phenotype among White and Black ACCORD participants
The relationship between time-varying achieved HbA1c and risk of coronary events depends on haptoglobin phenotype among White and Black ACCORD participants Open
Objective: Intensive glycemic therapy reduced coronary artery disease (CAD) events among White ACCORD study participants with the haptoglobin (Hp)2-2 phenotype, while participants without the Hp2-2 phenotype had no CAD benefit. The associa…
View article: The relationship between time-varying achieved HbA1c and risk of coronary events depends on haptoglobin phenotype among White and Black ACCORD participants
The relationship between time-varying achieved HbA1c and risk of coronary events depends on haptoglobin phenotype among White and Black ACCORD participants Open
Objective: Intensive glycemic therapy reduced coronary artery disease (CAD) events among White ACCORD study participants with the haptoglobin (Hp)2-2 phenotype, while participants without the Hp2-2 phenotype had no CAD benefit. The associa…
View article: Molecular Insights into IQSEC2 Disease
Molecular Insights into IQSEC2 Disease Open
Recent insights into IQSEC2 disease are summarized in this review as follows: (1) Exome sequencing of IQSEC2 patient DNA has led to the identification of numerous missense mutations that delineate at least six and possibly seven essential …
View article: Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction
Daily Brief Heat Therapy Reduces Seizures in A350V IQSEC2 Mice and Is Associated with Correction of AMPA Receptor-Mediated Synaptic Dysfunction Open
Purposeful induction of fever for healing, including the treatment of epilepsy, was used over 2000 years ago by Hippocrates. More recently, fever has been demonstrated to rescue behavioral abnormalities in children with autism. However, th…
View article: Molecular modeling of ARF6 dysregulation caused by mutations in IQSEC2
Molecular modeling of ARF6 dysregulation caused by mutations in IQSEC2 Open
IQSEC2 gene mutations are associated with epilepsy, autism, and intellectual disability. The primary function IQSEC2, mediated via its Sec 7 domain, is to act as a guanine nucleotide exchange factor for ARF6. We sought to develop a molecul…
View article: Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial
Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial Open
Objective: The haptoglobin (Hp)2-2 phenotype (~35-40% of people) is associated with increased oxidation and dysfunctional high-density lipoprotein (HDL) in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL-cho…
View article: Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial
Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial Open
OBJECTIVE The haptoglobin (Hp)2-2 phenotype (∼35–40% of people) is associated with increased oxidation and dysfunctional HDL in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL cholesterol and lower triglycer…
View article: Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial
Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial Open
Objective: The haptoglobin (Hp)2-2 phenotype (~35-40% of people) is associated with increased oxidation and dysfunctional high-density lipoprotein (HDL) in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL-cho…
View article: Reduction in seizure burden in a child with a A350V IQSEC2 mutation using heat therapy with a Jacuzzi
Reduction in seizure burden in a child with a A350V IQSEC2 mutation using heat therapy with a Jacuzzi Open
A child with a A350V IQSEC2 missense mutation resulting in drug‐resistant epilepsy stops having seizures when he has a fever. We demonstrate that raising the body temperature of the child using a commercial Jacuzzi dramatically reduces his…
View article: Reduction in seizure burden in a child with a A350V IQSEC2 mutation using a Jacuzzi
Reduction in seizure burden in a child with a A350V IQSEC2 mutation using a Jacuzzi Open
A child with a A350V IQSEC2 missense mutation resulting in drug resistant epilepsy stops having seizures when he has a fever. We demonstrate that raising the body temperature of the child using a commercial Jacuzzi dramatically reduces his…
View article: Pharmacological modulation of AMPA receptors rescues specific impairments in social behavior associated with the A350V Iqsec2 mutation
Pharmacological modulation of AMPA receptors rescues specific impairments in social behavior associated with the A350V Iqsec2 mutation Open
In this study we tested the hypothesis that pharmacological modulation of glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein plays a key ro…
View article: Housing of A350V IQSEC2 pups at 37 °C ambient temperature prevents seizures and permits the development of social vocalizations in adulthood
Housing of A350V IQSEC2 pups at 37 °C ambient temperature prevents seizures and permits the development of social vocalizations in adulthood Open
Raising the body temperature by raising the ambient temperature might provide a means to reduce seizures associated with the A350V IQSEC2 mutation and thereby allow for an improved neurodevelopmental trajectory.
View article: The Role of Haptoglobin Polymorphism in Cardiovascular Disease in the Setting of Diabetes
The Role of Haptoglobin Polymorphism in Cardiovascular Disease in the Setting of Diabetes Open
Atherosclerotic cardiovascular disease (CVD) is the major cause of morbidity and mortality in individuals with diabetes mellitus (DM). Preclinical models have suggested that excessive oxidative stress and hyperglycemia are directly respons…
View article: Precision medicine for the rescue of specific impairments in social behavior associated with the A350V<i>Iqsec2</i>mutation
Precision medicine for the rescue of specific impairments in social behavior associated with the A350V<i>Iqsec2</i>mutation Open
In this study we tested the hypothesis that precision medicine guided therapy targeting glutamatergic neurotransmission could rescue behavioral deficits exhibited by mice carrying a specific mutation in the Iqsec2 gene. The IQSEC2 protein …
View article: Structural and Functional Brain-wide Alterations in A350V IQSEC2 Mutant Mice Displaying Autistic-like Behavior
Structural and Functional Brain-wide Alterations in A350V IQSEC2 Mutant Mice Displaying Autistic-like Behavior Open
IQSEC2 is an X-linked gene which is associated with autism spectrum disorder (ASD), intellectual disability and epilepsy. IQSEC2 is a postsynaptic density protein, localized on excitatory synapses as part of the NMDA receptor complex and i…