Last update 01 Nov 2024

Dopamine Beta Hydroxylase Deficiency

Last update 01 Nov 2024

Basic Info

Synonyms

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

+ [11]

Introduction

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

Drugs associated with Dopamine Beta Hydroxylase Deficiency

Droxidopa

Target

adrenergic receptor

Mechanism

adrenergic receptor agonists

Active Org.

Lundbeck NA Ltd. [+2]

Originator Org.

Sumitomo Pharma Co., Ltd.

Active Indication

Diabetic Neuropathies [+6]

Inactive Indication

Attention Deficit Disorder With Hyperactivity [+15]

Drug Highest PhaseApproved

First Approval Ctry. / Loc.

First Approval Date17 Jan 1989

Clinical Trials associated with Dopamine Beta Hydroxylase Deficiency

NCT05687474 / RecruitingNot ApplicableIIT

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.

Start Date01 Sep 2022

Sponsor / Collaborator

Centre Hospitalier Universitaire de Liege

[+5]

NCT01927055 / TerminatedPhase 3

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.

Start Date01 Nov 2013

Sponsor / Collaborator

Chelsea Therapeutics, Inc.

NL-OMON22254 / SuspendedNot ApplicableIIT

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.

Start Date01 Feb 2013

Sponsor / Collaborator-

100 Clinical Results associated with Dopamine Beta Hydroxylase Deficiency

100 Translational Medicine associated with Dopamine Beta Hydroxylase Deficiency

0 Patents (Medical) associated with Dopamine Beta Hydroxylase Deficiency

158

Literatures (Medical) associated with Dopamine Beta Hydroxylase Deficiency

13 Mar 2024·Science Translational MedicineQ1 · MEDICINE

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

Q1 · MEDICINE

Article

Author: 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.

01 Sep 2022·Biomedicine & Pharmacotherapy

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

Article

Author: 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.

01 Jun 2022·Acta PaediatricaQ4 · MEDICINE

The cause of eyelid ptosis, orthostatic hypotension and exercise intolerance

Q4 · MEDICINE

Article

Author: 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.

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