更新于：2024-11-01

Primary hyperoxaluria type III

原发性高草酸尿症III型

更新于：2024-11-01

基本信息

别名

HP3、HYPEROXALURIA, PRIMARY, TYPE III、Primary Hyperoxaluria Type III

+ [3]

简介

Recessively inherited primary hyperoxaluria due to mitochondrial 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene mutations.

关联

项与原发性高草酸尿症III型相关的药物

Nedosiran

靶点

LDHA

作用机制

LDHA抑制剂

在研机构

Dicerna Pharmaceuticals, Inc. [+1]

原研机构

Novo Nordisk, Inc.

在研适应症

原发性高草酸尿症1型 [+3]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2023-09-29

Stiripentol

司替戊醇

靶点

GABAA receptor x L-lactate dehydrogenase

作用机制

GABAA receptor激动剂 [+1]

在研机构

Biocodex SAS [+3]

原研机构

Biocodex SAS

在研适应症

CDKL5缺乏症 [+7]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2007-01-03

项与原发性高草酸尿症III型相关的临床试验

NCT06465472 / Not yet recruiting临床3期

Evaluation of the Efficacy and Safety of Stiripentol in Patients 6 Years and Older With Primary Hyperoxaluria Type 1, 2 or 3

Evaluation of the efficacy and safety of stiripentol in patients 6 years and older with primary hyperoxaluria type 1, 2 or 3.

开始日期2024-08-01

申办/合作机构

Biocodex SAS

[+1]

NCT05001269 / Recruiting临床2期

A Phase 2 Open-Label Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of Nedosiran in Pediatric Patients From Birth to 11Years of Age With Primary Hyperoxaluria and Relatively Intact Renal Function

The aim of this study is to evaluate nedosiran in participants 11 years of age and younger who have Primary Hyperoxaluria with relatively intact renal function.

开始日期2022-02-22

申办/合作机构

Dicerna Pharmaceuticals, Inc.

NCT04542590 / Active, not recruitingN/A

A Natural History Study of Patients With Genetically Confirmed Primary Hyperoxaluria Type 3 and, as Applicable Per Age, a History of Stone Events

This is a natural history study of adults, adolescents, and children (starting at birth) with genetically confirmed primary hyperoxaluria type 3 (PH3) who have a history of stone events during the last 3 years and/or the presence of pre existing stones detected by renal ultrasound at screening.

开始日期2021-09-09

申办/合作机构

Dicerna Pharmaceuticals, Inc.

100 项与原发性高草酸尿症III型相关的临床结果

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100 项与原发性高草酸尿症III型相关的转化医学

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0 项与原发性高草酸尿症III型相关的专利（医药）

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项与原发性高草酸尿症III型相关的文献（医药）

2024-09-01·Biochemistry and Biophysics Reports

4-hydroxy-2-oxoglutarate metabolism in a mouse model of Primary Hyperoxaluria Type 3

Article

作者: Assimos, Dean G ; Wood, Kyle D ; Cunneely, Owen P ; Fargue, Sonia ; Knight, John ; Li, Xingsheng

Primary Hyperoxaluria Type 3 (PH3) results from 4-hydroxy-2-oxoglutarate (HOG) aldolase (HOGA) deficiency, which causes an increase in endogenous oxalate synthesis leading to calcium oxalate kidney stone disease. The mechanisms underlying HOG metabolism and increased oxalate synthesis in PH3 are not well understood. We used a Hoga1 knock-out mouse model of PH3 to investigate two aspects of HOG metabolism: reduction to dihydroxyglutarate (DHG), a pathway that may limit oxalate synthesis in PH3, and metabolism to glyoxylate, which is a direct precursor to oxalate. The metabolism of HOG to DHG was highest in liver and kidney cortical tissue, enhanced in the cytosolic compartment of the liver, and preferred NADPH as a cofactor. In the absence of HOGA, HOG to glyoxylate aldolase activity was highest in liver mitoplasts, with no activity present in brain tissue lysates. These findings will assist in the identification of enzymes responsible for the metabolism of HOG to DHG and glyoxylate, which may lead to novel therapeutic approaches to limit oxalate synthesis in those afflicted with PH3.

2015-01-01·World Journal of Nephrology

Primary and secondary hyperoxaluria: Understanding the enigma

Review

作者: Ürekli, Hatice Melda ; Atta, Mohamed G ; Bhasin, Bhavna

Hyperoxaluria is characterized by an increased urinary excretion of oxalate. Primary and secondary hyperoxaluria are two distinct clinical expressions of hyperoxaluria. Primary hyperoxaluria is an inherited error of metabolism due to defective enzyme activity. In contrast, secondary hyperoxaluria is caused by increased dietary ingestion of oxalate, precursors of oxalate or alteration in intestinal microflora. The disease spectrum extends from recurrent kidney stones, nephrocalcinosis and urinary tract infections to chronic kidney disease and end stage renal disease. When calcium oxalate burden exceeds the renal excretory ability, calcium oxalate starts to deposit in various organ systems in a process called systemic oxalosis. Increased urinary oxalate levels help to make the diagnosis while plasma oxalate levels are likely to be more accurate when patients develop chronic kidney disease. Definitive diagnosis of primary hyperoxaluria is achieved by genetic studies and if genetic studies prove inconclusive, liver biopsy is undertaken to establish diagnosis. Diagnostic clues pointing towards secondary hyperoxaluria are a supportive dietary history and tests to detect increased intestinal absorption of oxalate. Conservative treatment for both types of hyperoxaluria includes vigorous hydration and crystallization inhibitors to decrease calcium oxalate precipitation. Pyridoxine is also found to be helpful in approximately 30% patients with primary hyperoxaluria type 1. Liver-kidney and isolated kidney transplantation are the treatment of choice in primary hyperoxaluria type 1 and type 2 respectively. Data is scarce on role of transplantation in primary hyperoxaluria type 3 where there are no reports of end stage renal disease so far. There are ongoing investigations into newer modalities of diagnosis and treatment of hyperoxaluria. Clinical differentiation between primary and secondary hyperoxaluria and further between the types of primary hyperoxaluria is very important because of implications in treatment and diagnosis. Hyperoxaluria continues to be a challenging disease and a high index of clinical suspicion is often the first step on the path to accurate diagnosis and management.