Long-term bumetanide administration altered behavioral pattern in mosaic Down’s Syndrome: A case report

Gharaylou, Zeinab; Shafaghi, Lida; Pestehei, Seyed Khalil; Hadjighassem, Mahmoudreza

doi:10.1080/21622965.2021.2007481

Cited by 4 publications

(3 citation statements)

References 54 publications

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“…Also, down-regulation of NKCC1 by RNA interference due to restoring neuronal chloride homeostasis in mouse models was successful (226). In our pervious case-control study, bumetanide, a selective NKCC1 inhibitor prescribed for 18 months, showed encouraging results in reversing certain behavioral abnormalities in a fourteen-year-old boy with genetically proven mosaic Down's syndrome (229).…”

Section: Down Syndrome (Ds)mentioning

confidence: 94%

Role of Ion Channelopathy in Neurological Diseases; Role of Gabaergic System Connectivity and Dysfunction in Neurological Disorders

Hadjighassem

2024

IJCCR

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The inhibitory neurotransmitter γ-aminobutyric acid (GABA) is produced by GABAergic neurons and is essential in human neurodevelopmental stage. It has a variety of functions in the CNS and exerts its functions by binding to several GABA receptors including ionotropic and ligand-gated chloride channels. The CNS neurotransmitters endorphin, dopamine, serotonin or 5-hydroxytryptamine (5-HT), norepinephrine (NE), and acetylcholine (ACh) are all regulated by GABA. Additionally, GABA has a role in the pathogenesis of some CNS-related diseases. This study discusses the function of GABA in human neurodevelopmental stages and its interactions with other CNS neurotransmitters. The significance of Cl- homeostasis in GABA receptor activities, which regulate Cl--mediated neurotransmission in the CNS, is also stressed. Furthermore, the relationship between intracellular Cl- changes and CNS diseases such as Down syndrome (DS), epilepsy, schizophrenia, and autism spectrum disorders (ASD) is discussed. The study also highlights the potential application of bumetanide to regulate intracellular Cl- levels and treat CNS disease symptoms. The article comes to the conclusion that understanding the function of GABA and chloride homeostasis in clinical CNS diseases is beneficial in developing innovative treatment options, and the potential of bumetanide offers a new direction for research and clinical intervention.

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Section: Down Syndrome (Ds)mentioning

confidence: 94%

Role of Ion Channelopathy in Neurological Diseases; Role of Gabaergic System Connectivity and Dysfunction in Neurological Disorders

Hadjighassem

2024

IJCCR

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“…The efficacy of bumetanide for cognitive improvement in children and adolescents with Down syndrome is currently being assessed in a phase II controlled study (EudraCT Number: 2015-005780-16), and a case report suggests positive effects. 49 Finally, memantine, a N-methyl-D-aspartate receptor antagonist, currently in use for Alzheimer disease for its neuroprotective effects, showed quite promising results in Down syndrome mouse models. 50,51 However, despite some initial results in a pilot trial conducted on young adults with Down syndrome, 52 in a recent phase II clinical trial carried out on 185 individuals with Down syndrome, the drug failed to achieve cognitive improvement.…”

Section: Symptomatic Therapy: Neurotransmitter-based Strategiesmentioning

confidence: 99%

“…The NKCC1 is currently gaining increased attention as a possible therapeutic target for treating Down syndrome, as it produces a shift towards more hyperpolarizing GABAergic responses. The efficacy of bumetanide for cognitive improvement in children and adolescents with Down syndrome is currently being assessed in a phase II controlled study (EudraCT Number: 2015‐005780‐16), and a case report suggests positive effects 49 . Finally, memantine, a N‐methyl‐D‐aspartate receptor antagonist, currently in use for Alzheimer disease for its neuroprotective effects, showed quite promising results in Down syndrome mouse models 50,51 .…”

Section: From Symptomatic To Disease‐modifying Therapymentioning

confidence: 99%

State‐of‐the‐art therapy for Down syndrome

Lorenzón

Musoles-Lleó

Turrisi

et al. 2023

Develop Med Child Neuro

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Down syndrome is the most common chromosomal disorder, caused by a third copy of all or part of chromosome 21 (HSA21), and the most complex and prevalent genetic cause of intellectual disability. 1 It is a chronic, multifactorial disorder that affects brain development and function, impairing cognition and adaptive behaviour. 2 Moreover, Down syndrome co-occurs with autism and epilepsy and is considered a genetic form of Alzheimer disease. 3 In addition, individuals with Down syndrome have a high prevalence of endocrine disorders and obesity, leading to type 2 diabetes, insulin resistance, and neuroinflammation, 4 which, in turn, contribute to cognitive deficits.In the last decade, an important effort was made to better understand the pathogenetic mechanisms involved in Down

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