更新于：2024-11-01

Dopamine Beta Hydroxylase Deficiency

多巴胺β-羟化酶缺乏症

更新于：2024-11-01

基本信息

别名

Congenital dopamine beta hydroxylase deficiency、DBH deficiency、DOPAMINE BETA-HYDROXYLASE DEFICIENCY, CONGENITAL

+ [11]

简介

A very rare primary monoamine neurotransmitter synthesis disorder with norepinephrine and adrenaline deficiency that leads to young-onset severe orthostatic hypotension and eyelid ptosis.

关联

项与多巴胺β-羟化酶缺乏症相关的药物

Droxidopa

屈昔多巴

靶点

adrenergic receptor

作用机制

adrenergic receptor激动剂

在研机构

Lundbeck NA Ltd. [+2]

原研机构

Sumitomo Pharma Co., Ltd.

在研适应症

糖尿病性神经病变 [+6]

非在研适应症

注意缺陷障碍伴多动 [+15]

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期1989-01-17

项与多巴胺β-羟化酶缺乏症相关的临床试验

NCT05687474 / RecruitingN/AIIT

Universal Genomic Newborn Screening in the Wallonia-Brussels Federation: Baby Detect

Newborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life.
Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents.

开始日期2022-09-01

申办/合作机构

Centre Hospitalier Universitaire de Liege

[+5]

NCT01927055 / Terminated临床3期

A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy

Evaluate the clinical efficacy and safety of droxidopa versus placebo over a 17 week (maximum) treatment period in patients with symptomatic NOH.

开始日期2013-11-01

申办/合作机构

Chelsea Therapeutics, Inc.

NL-OMON22254 / SuspendedN/AIIT

The role of noradrenaline (NA) in Eye Movement Desensitization and Reprocessing (EMDR). Part I: The effects of NA-antagonist propranolol on the plasticity of emotionally arousing episodic memories.

开始日期2013-02-01

申办/合作机构-

100 项与多巴胺β-羟化酶缺乏症相关的临床结果

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100 项与多巴胺β-羟化酶缺乏症相关的转化医学

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0 项与多巴胺β-羟化酶缺乏症相关的专利（医药）

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158

项与多巴胺β-羟化酶缺乏症相关的文献（医药）

2024-03-13·Science Translational Medicine1区 · 医学

Cortical hyperexcitability in mouse models and patients with amyotrophic lateral sclerosis is linked to noradrenaline deficiency

1区 · 医学

Article

作者: Ye, XiaoQian ; Logunov, Evgeny ; Kessler, Pascal ; Sinniger, Jérôme ; Brunet, Aurore ; René, Frédérique ; Douchamps, Vincent ; Kan, Vanessa Wing Yin ; Rouaux, Caroline ; Andry, Virginie ; Gunes, Zeynep ; Stuart-Lopez, Geoffrey ; Goutagny, Romain ; Dieterle, Stéphane ; Dirrig-Grosch, Sylvie ; Benetton, Cristina ; Gorin, Charlotte ; Liebscher, Sabine ; Goumon, Yannick ; Gilet, Johan ; Fischer, Mathieu ; Scekic-Zahirovic, Jelena ; Dupuis, Luc ; Marchand-Pauvert, Véronique ; Guillot, Simon J ; Pradat, Pierre-François ; Trombini, Margaux ; Megat, Salim

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in the motor cortex, brainstem, and spinal cord. Despite decades of research, ALS remains incurable, challenging to diagnose, and of extremely rapid progression. A unifying feature of sporadic and familial forms of ALS is cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, and is sufficient to trigger neurodegeneration in rodents. Using electrocorticography in the Sod1 G86R and Fus Δ NLS/+ ALS mouse models and standard electroencephalography recordings in patients with sporadic ALS, we demonstrate a deficit in theta-gamma phase-amplitude coupling (PAC) in ALS. In mice, PAC deficits started before symptom onset, and in patients, PAC deficits correlated with the rate of disease progression. Using mass spectrometry analyses of CNS neuropeptides, we identified a presymptomatic reduction of noradrenaline (NA) in the motor cortex of ALS mouse models, further validated by in vivo two-photon imaging in behaving SOD1 G93A and Fus Δ NLS/+ mice, that revealed pronounced reduction of locomotion-associated NA release. NA deficits were also detected in postmortem tissues from patients with ALS, along with transcriptomic alterations of noradrenergic signaling pathways. Pharmacological ablation of noradrenergic neurons with DSP-4 reduced theta-gamma PAC in wild-type mice and administration of a synthetic precursor of NA augmented theta-gamma PAC in ALS mice. Our findings suggest theta-gamma PAC as means to assess and monitor cortical dysfunction in ALS and warrant further investigation of the NA system as a potential therapeutic target.

2022-09-01·Biomedicine & Pharmacotherapy

In vitro and in vivo pharmacological characterization of dasotraline, a dual dopamine and norepinephrine transporter inhibitor in vivo

Article

作者: Fang, Q Kevin ; Hardy, Larry W ; Lew, Robert ; Quinton, Maria S ; Schreiber, Rudy ; Campbell, Una

Inhibitors of dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) are effective treatments for neuropsychiatric diseases. Dasotraline [(1R,4 S)- 4-(3,4-dichlorophenyl)- 1,2,3,4-tetrahydro-1-naphthalenamine, also known as SEP-225289) was evaluated for its inhibitory potency at DAT, NET and SERT using in vitro and in vivo assays. In vitro radiometric functional uptake studies showed preferential inhibition by dasotraline of hDAT (IC₅₀ =3 nM) and hNET (IC₅₀ =4 nM relative to hSERT(IC₅₀ =15 nM). In mouse ex vivo occupancy studies, dasotraline demonstrated total plasma concentration-dependent occupancy at DAT, NET and SERT. Determination of the TO₅₀ (50% transporter occupancy) were 32, 109 and 276 ng/ml, respectively. In SPECT imaging studies in baboons, dasotraline (0.2 mg/kg iv) displaced radiotracer binding to DAT by 87% but only 20% at NET and SERT. Rat microdialysis studies were performed in prefrontal cortex and striatum. Dasotraline produced sustained (>4 h) increases in dopamine and norepinephrine concentrations. Dasotraline was also more potent at increasing synaptic dopamine in the striatum, and norepinephrine in the prefrontal cortex than serotonin in these regions. In summary, dasotraline preferentially inhibits DAT and NET relative to SERT. Together, the occupancy and neurochemical profile of dasotraline provide a mechanistic basis for the treatment of diseases that have an underlying causality involving dopamine and norepinephrine dysfunction.

2022-06-01·Acta Paediatrica4区 · 医学

The cause of eyelid ptosis, orthostatic hypotension and exercise intolerance

4区 · 医学

Article

作者: Monnens, Leo

AbstractTo provide more insight in the delay in diagnosis and expectation of treatment adapted for the paediatrician, the data were collected from patients described with dopamine beta‐hydroxylase deficiency are evaluated. More insight in clinical features of dopamine beta‐hydroxylase deficiency consisting mainly of eyelid ptosis, orthostatic hypotension, hypoglycaemia and exercise intolerance, explains the delay in diagnosis of this congenital disorder, although all symptoms some more concealed are present. An increasing experience by L‐DOPS, a resurrection for the patient, allows recommendations for early treatment. An explanation for the delay in diagnosis is provided together with the advice for treatment.