The Experts below are selected from a list of 1772487 Experts worldwide ranked by ideXlab platform
Kevin A Strauss - One of the best experts on this subject based on the ideXlab platform.
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branched chain α ketoacid dehydrogenase deficiency maple syrup urine Disease Treatment biomarkers and outcomes
Molecular Genetics and Metabolism, 2020Co-Authors: Kevin A Strauss, Vincent J Carson, Kyle Soltys, Millie Young, Lauren E Bowser, Erik G Puffenberger, Karlla W Brigatti, Katie B WilliamsAbstract:Abstract Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain α-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine Disease (MSUD) phenotype. We collected data about Treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard instruments were used to measure neuropsychiatric outcomes. Despite advances in clinical care, classic MSUD remains a morbid and potentially fatal disorder. Stringent dietary therapy maintains metabolic variables within acceptable limits but is challenging to implement, fails to restore appropriate concentration relationships among circulating amino acids, and does not fully prevent cognitive and psychiatric disabilities. Liver transplantation eliminates the need for a prescription diet and safeguards patients from life-threatening metabolic crises, but is associated with predictable morbidities and does not reverse pre-existing neurological sequelae. There is a critical unmet need for safe and effective Disease-modifying therapies for MSUD which can be implemented early in life. The biochemistry and physiology of MSUD and its response to liver transplantation afford key insights into the design of new therapies based on gene replacement or editing.
Katie B Williams - One of the best experts on this subject based on the ideXlab platform.
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branched chain α ketoacid dehydrogenase deficiency maple syrup urine Disease Treatment biomarkers and outcomes
Molecular Genetics and Metabolism, 2020Co-Authors: Kevin A Strauss, Vincent J Carson, Kyle Soltys, Millie Young, Lauren E Bowser, Erik G Puffenberger, Karlla W Brigatti, Katie B WilliamsAbstract:Abstract Over the past three decades, we studied 184 individuals with 174 different molecular variants of branched-chain α-ketoacid dehydrogenase activity, and here delineate essential clinical and biochemical aspects of the maple syrup urine Disease (MSUD) phenotype. We collected data about Treatment, survival, hospitalization, metabolic control, and liver transplantation from patients with classic (i.e., severe; n = 176), intermediate (n = 6) and intermittent (n = 2) forms of MSUD. A total of 13,589 amino acid profiles were used to analyze leucine tolerance, amino acid homeostasis, estimated cerebral amino acid uptake, quantitative responses to anabolic therapy, and metabolic control after liver transplantation. Standard instruments were used to measure neuropsychiatric outcomes. Despite advances in clinical care, classic MSUD remains a morbid and potentially fatal disorder. Stringent dietary therapy maintains metabolic variables within acceptable limits but is challenging to implement, fails to restore appropriate concentration relationships among circulating amino acids, and does not fully prevent cognitive and psychiatric disabilities. Liver transplantation eliminates the need for a prescription diet and safeguards patients from life-threatening metabolic crises, but is associated with predictable morbidities and does not reverse pre-existing neurological sequelae. There is a critical unmet need for safe and effective Disease-modifying therapies for MSUD which can be implemented early in life. The biochemistry and physiology of MSUD and its response to liver transplantation afford key insights into the design of new therapies based on gene replacement or editing.
Xose M. Dopazo - One of the best experts on this subject based on the ideXlab platform.
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targeting the neuronal calcium sensor dream with small molecules for huntington s Disease Treatment
Scientific Reports, 2019Co-Authors: Diego A. Peraza, Pilar Cercós, Laura Lagartera, Paz Gonzalez, Xose M. Dopazo, Alejandro LopezhurtadoAbstract:DREAM, a neuronal calcium sensor protein, has multiple cellular roles including the regulation of Ca2+ and protein homeostasis. We recently showed that reduced DREAM expression or blockade of DREAM activity by repaglinide is neuroprotective in Huntington’s Disease (HD). Here we used structure-based drug design to guide the identification of IQM-PC330, which was more potent and had longer lasting effects than repaglinide to inhibit DREAM in cellular and in vivo HD models. We disclosed and validated an unexplored ligand binding site, showing Tyr118 and Tyr130 as critical residues for binding and modulation of DREAM activity. IQM-PC330 binding de-repressed c-fos gene expression, silenced the DREAM effect on KV4.3 channel gating and blocked the ATF6/DREAM interaction. Our results validate DREAM as a valuable target and propose more effective molecules for HD Treatment.
Alejandro Lopezhurtado - One of the best experts on this subject based on the ideXlab platform.
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targeting the neuronal calcium sensor dream with small molecules for huntington s Disease Treatment
Scientific Reports, 2019Co-Authors: Diego A. Peraza, Pilar Cercós, Laura Lagartera, Paz Gonzalez, Xose M. Dopazo, Alejandro LopezhurtadoAbstract:DREAM, a neuronal calcium sensor protein, has multiple cellular roles including the regulation of Ca2+ and protein homeostasis. We recently showed that reduced DREAM expression or blockade of DREAM activity by repaglinide is neuroprotective in Huntington’s Disease (HD). Here we used structure-based drug design to guide the identification of IQM-PC330, which was more potent and had longer lasting effects than repaglinide to inhibit DREAM in cellular and in vivo HD models. We disclosed and validated an unexplored ligand binding site, showing Tyr118 and Tyr130 as critical residues for binding and modulation of DREAM activity. IQM-PC330 binding de-repressed c-fos gene expression, silenced the DREAM effect on KV4.3 channel gating and blocked the ATF6/DREAM interaction. Our results validate DREAM as a valuable target and propose more effective molecules for HD Treatment.
Michael S Kaminer - One of the best experts on this subject based on the ideXlab platform.
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benign familial pemphigus hailey hailey Disease Treatment with the pulsed carbon dioxide laser
Dermatologic Surgery, 1998Co-Authors: Dany J Touma, Madeline Krauss, David S Feingold, Michael S KaminerAbstract:background Benign familial pemphigus (BFP) is a chronic blistering Disease with significant morbidity. Surgical methods are often needed to control flares in difficult cases. objective To describe the response of BFP to vaporization with a pulsed carbon dioxide (CO2) laser. methods A 38-year-old woman with chest and axillary involvement unresponsive to conventional therapy was treated with the UltraPulse 5000 Laser (Coherent Medical Group, Palo Alto, CA). After active sites of BFP showed good response to Treatment, we treated uninvolved skin of the left axilla to assess the efficacy of prophylactic therapy. results Treatment of affected areas, except biopsy sites, resulted in clearing of active lesions after 1–2 weeks. We noted striking sparing of the treated areas from developing subsequent Disease. The region that was later treated prophylactically has shown minor, asymptomatic recurrence of BFP in less than 5% of the area treated over an 18-month follow-up period. conclusion The pulsed carbon dioxide laser is a useful modality in Treatment of BFP. In our patient, prophylactic Treatment led to near complete eradication of Disease in the treated area. A controlled, larger study is needed to confirm our results, and to determine optimal laser parameters. Long-term effects and duration of remission remain to be determined.
