公开(公告)号：US20190117611A1

公开(公告)日：2019-04-25

申请号：US16094828

申请日：2017-04-18

申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education

发明人： Gerard Vockley ,  Al-Walid A. Mohsen

IPC分类号： A61K31/225 ,  A61P3/00

摘要： Methods of treating propionic acidemia (PA), methylmalonic acidemia (MMA) and fatty acid oxidation disorders are described. The methods include administering an anaplerotic agent that can directly enter the tricarboxylic acid cycle, such as a succinate derivative or pro-drug, for example trisuccinylglycerol (TSG). Methods of restoring tricarboxylic acid (TCA) cycle function in a cell deficient for propionyl-CoA carboxylase (PCC) or methylmalonyl-CoA mutase (MUT) by contacting the cell with a succinate derivative or pro-drug, such as TSG, are also described.

公开(公告)号：US20240075025A1

公开(公告)日：2024-03-07

申请号：US18376188

申请日：2023-10-03

申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education

发明人： Al-Walid A. Mohsen ,  Gerard Vockley

IPC分类号： A61K31/496 ,  A61K31/426 ,  A61K31/495 ,  A61K45/06 ,  A61P3/08

CPC分类号： A61K31/496 ,  A61K31/426 ,  A61K31/495 ,  A61K45/06 ,  A61P3/08 ,  A61K38/45

摘要： Methods of treating mitochondrial fatty acid β-oxidation and/or transport disorders arising from mutant proteins in the mitochondrial fatty acid β-oxidation and transport metabolic pathways in patients are provided. The methods modulate the mitochondrial fatty acid β-oxidation pathway at the last step so that the product of the mutant protein accumulates and stabilizes the mutant protein and/or the substrate(s)/product(s) of the downstream reactions accumulate and possibly bind to allosteric sites on the mutant protein to stabilize it. Trimetazidine pharmacodynamics function as such in the β-oxidation pathway. Further, a synergistic effect is observed where a trimetazidine and PPARδ agonist combination enhanced enzyme activity and presence significantly more than either alone.

公开(公告)号：US11813258B2

公开(公告)日：2023-11-14

申请号：US17344084

申请日：2021-06-10

申请人： University of Pittsburgh—Of the Commonwealth System of Higher Education

发明人： Al-Walid A. Mohsen ,  Gerard Vockley

IPC分类号： A61K31/496 ,  A61P3/08 ,  A61K31/426 ,  A61K45/06 ,  A61K31/495 ,  A61K38/45

CPC分类号： A61K31/496 ,  A61K31/426 ,  A61K31/495 ,  A61K45/06 ,  A61P3/08 ,  A61K38/45 ,  A61K31/426 ,  A61K2300/00 ,  A61K31/495 ,  A61K2300/00

摘要： Methods of treating mitochondrial fatty acid β-oxidation and/or transport disorders arising from mutant proteins in the mitochondrial fatty acid β-oxidation and transport metabolic pathways in patients are provided. The methods modulate the mitochondrial fatty acid β-oxidation pathway at the last step so that the product of the mutant protein accumulates and stabilizes the mutant protein and/or the substrate(s)/product(s) of the down stream reactions accumulate and possibly bind to allosteric sites on the mutant protein to stabilize it. Trimetazidine pharmacodynamics function as such in the β-oxidation pathway. Further, a synergistic effect is observed where trimetazidine and PPARδ agonist combination enhanced enzyme activity and presence significantly more than either alone.

公开(公告)号：US20190142893A1

公开(公告)日：2019-05-16

申请号：US16098322

申请日：2017-05-05

申请人： University of Pittsburgh- Of the Commonwealth System of Higher Education

发明人： Al-Walid A. Mohsen ,  Gerard Vockley ,  Yudong Wang ,  Peter Wipf

IPC分类号： A61K38/06 ,  A61P3/00 ,  A61P9/00 ,  A61P19/00 ,  A61K31/4468

摘要： A method is provided for treating a fatty acid oxidation metabolic condition, such as an inborn error of fatty acid oxidation or oxidative phosphorylation, and/or hypoglycemia, rhabdomyolysis, or cardiomyopathy in a patient. A mitochondrial-targeted electron, radical, or ROS-scavenging agent is administered to the patient in an amount effective to treat, mitigate or prevent any fatty acid oxidation metabolic condition, such as inborn errors of fatty acid oxidation or oxidative phosphorylation, and/or hypoglycemia, rhabdomyolysis, or cardiomyopathy in a patient.

公开(公告)号：US20180023113A1

公开(公告)日：2018-01-25

申请号：US15656414

申请日：2017-07-21

申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education

发明人： Al-Walid A. Mohsen ,  Gerard Vockley

IPC分类号： C12Q1/32 ,  G01N21/64

CPC分类号： C12Q1/32 ,  C12Y103/99003 ,  G01N21/6428 ,  G01N21/6452 ,  G01N2800/04

摘要： Provided herein are methods of measuring acyl-CoA dehydrogenase activity in a biological sample in a multiwell microplate setting.

公开(公告)号：US12128038B2

公开(公告)日：2024-10-29

申请号：US17560783

申请日：2021-12-23

申请人： University of Pittsburgh-Of the Commonwealth System of Higher Education

发明人： Gerard Vockley ,  Peter Wipf ,  Al-Walid A. Mohsen

IPC分类号： A61K31/454 ,  A61K31/4468 ,  A61P7/08

CPC分类号： A61K31/454 ,  A61K31/4468 ,  A61P7/08

摘要： Methods of treating a patient having an organic acidemia or a defect in mitochondria chain oxidation are provided. The methods comprise treating the patient with an effective amount of a mitochondria-targeting reactive oxygen species scavenger.

公开(公告)号：US20180318381A1

公开(公告)日：2018-11-08

申请号：US15769992

申请日：2016-10-21

申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education

发明人： Gerard Vockley ,  Al-Walid A. Mohsen

IPC分类号： A61K38/07 ,  A61K31/225 ,  A61K31/277 ,  A61K31/7072 ,  A61P29/00 ,  A61P3/00

CPC分类号： A61K38/07 ,  A61K31/215 ,  A61K31/225 ,  A61K31/277 ,  A61K31/56 ,  A61K31/7072 ,  A61P3/00 ,  A61P29/00

摘要： Provided herein are methods of treating long-chain fatty acid disorders, conditions, such as rhabdomyolysis, associated with inflammation and/or long-chain fatty acid disorders, and inflammation associated with long-chain fatty acid disorders.

公开(公告)号：US09283200B2

公开(公告)日：2016-03-15

申请号：US14515298

申请日：2014-10-15

申请人： University of Pittsburgh-of the Commonwealth System of Higher Education

发明人： Al-Walid Mohsen Mohamed ,  Gerard Vockley

IPC分类号： A61K31/19 ,  A61K31/12 ,  A61K31/192 ,  A61K31/216

CPC分类号： A61K31/192 ,  A61K31/216 ,  A61K2300/00

摘要： The present invention provides for methods and compositions for treating medium chain acyl-CoA dehydrogenase deficiency. It is based, at least in part, on the discovery that phenylbutyrate can serve as a substrate for medium chain acyl-CoA dehydrogenase. In non-limiting embodiments, phenylbutyrate and/or another source of phenylacetate is administered as a chaperone treatment to patients suffering from medium chain acyl-CoA dehydrogenase deficiency.

摘要翻译： 本发明提供了用于处理中链酰基辅酶A脱氢酶缺陷的方法和组合物。 至少部分地基于苯丁酸酯可以作为中链酰基辅酶A脱氢酶的底物的发现。 在非限制性实施方案中，苯丙酸苯酯和/或苯乙酸乙酯的另一来源作为伴侣伴侣治疗给予患有中链酰基辅酶A脱氢酶缺陷的患者。

公开(公告)号：US20150216824A1

公开(公告)日：2015-08-06

申请号：US14515298

申请日：2014-10-15

申请人： University of Pittsburgh - of the Commonwealth System of Higher Education

发明人： AI-Walid Mohsen Mohamed ,  Gerard Vockley

IPC分类号： A61K31/192 ,  A61K31/216

CPC分类号： A61K31/192 ,  A61K31/216 ,  A61K2300/00

摘要： The present invention provides for methods and compositions for treating medium chain acyl-CoA dehydrogenase deficiency. It is based, at least in part, on the discovery that phenylbutyrate can serve as a substrate for medium chain acyl-CoA dehydrogenase. In non-limiting embodiments, phenylbutyrate and/or another source of phenylacetate is administered as a chaperone treatment to patients suffering from medium chain acyl-CoA dehydrogenase deficiency.

摘要翻译： 本发明提供了用于处理中链酰基辅酶A脱氢酶缺陷的方法和组合物。 至少部分地基于苯丁酸酯可以作为中链酰基辅酶A脱氢酶的底物的发现。 在非限制性实施方案中，苯丙酸苯酯和/或苯乙酸乙酯的另一来源作为伴侣伴侣治疗给予患有中链酰基辅酶A脱氢酶缺陷的患者。

公开(公告)号：US20210338624A1

公开(公告)日：2021-11-04

申请号：US17369268

申请日：2021-07-07

申请人： University of Pittsburgh - Of the Commonwealth System of Higher Education

发明人： Gerard Vockley ,  Al-Walid A. Mohsen

IPC分类号： A61K31/225 ,  A61P3/00 ,  C07C69/66

摘要： Methods of treating propionic acidemia (PA), methylmalonic acidemia (MMA) and fatty acid oxidation disorders are described. The methods include administering an anaplerotic agent that can directly enter the tricarboxylic acid cycle, such as a succinate derivative or pro-drug, for example trisuccinylglycerol (TSG). Methods of restoring tricarboxylic acid (TCA) cycle function in a cell deficient for propionyl-CoA carboxylase (PCC) or methylmalonyl-CoA mutase (MUT) by contacting the cell with a succinate derivative or pro-drug, such as TSG, are also described.