Bumetanide autism

No abstract text is available yet for this article.

No abstract text is available yet for this article.

AIM: Bumetanide, a diuretic agent, that reduces intracellular chloride-thereby reinforcing GABAergic inhibition-has been reported to improve core symptoms of autism in children. Given the positive results reported from French trials of bumetanide in children with autism, we decided to evaluate its effects in a small-scale pilot study, in advance of a larger randomised controlled study (RCT). METHODS: This was an open-label three-month trial of bumetanide on six children (five boys), aged 3-14 years with autism...

There are currently no approved pharmacological treatments to improve social reciprocity and limit repetitive and rigid behaviors in autism spectrum disorder (ASD). We describe the design of two Phase III studies evaluating the efficacy/safety of bumetanide oral liquid formulation in ASD. These are international, multicenter, randomized, double-blind, placebo-controlled studies in children and adolescents with ASD aged 7 to 17 years (n = 200; study 1), or younger children with ASD aged 2 to 6 years (n = 200; study 2)...

Aberrant expression ratio of Cl- transporters, NKCC1 and KCC2, is implicated in several brain conditions. NKCC1 inhibition by the FDA-approved diuretic drug, bumetanide, rescues core symptoms in rodent models and/or clinical trials with patients. However, bumetanide has a strong diuretic effect due to inhibition of the kidney Cl- transporter NKCC2, creating critical drug compliance issues and health concerns. Here, we report the discovery of a new chemical class of selective NKCC1 inhibitors and the lead drug candidate ARN23746...

OBJECTIVE: Recent trials have indicated positive effects of bumetanide in autism spectrum disorder (ASD). We tested efficacy of bumetanide on core symptom domains using a single center, parallel-group, participant-randomized, double-blind, placebo-controlled phase-2 superiority trial in a tertiary hospital in the Netherlands. METHOD: Unmedicated children aged 7 to 15 years with ASD and IQ ≥55 were block-randomized 1:1 to oral-solution bumetanide versus placebo, titrated to a maximum of 1...

OBJECTIVE: To examine the efficacy of pharmacological treatments for restricted and repetitive behaviors (RRB) in autism spectrum disorders (ASD). METHOD: We searched PubMed, Embase, and CENTRAL to identify all double-blind, randomized, placebo-controlled trials that examined the efficacy of pharmacological agents in the treatment of ASD and measured RRB as an outcome. Our primary outcome was the standardized mean difference in rating scales of RRB. RESULTS: We identified 64 randomized, placebo-controlled trials involving 3,499 participants with ASD...

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease that affects multiple organs including the brain. TSC is strongly associated with broad neurodevelopmental disorders, including autism spectrum disorder symptomatology. Preclinical TSC studies have indicated altered neuronal chloride homeostasis affecting the polarity of γ-aminobutyric acid (GABA) ergic transmission as a potential treatment target. Bumetanide, a selective NKCC1 chloride importer antagonist, may attenuate depolarizing GABA action, and in that way reduce disease burden...

Introduction: Autism Spectrum Disorder (ASD) is characterized by several impairments in communications and social interactions, as well as restricted interests or stereotyped behaviors. Interventions applied for this disorder are based on multi-modal approaches, including pharmacotherapy. No definitive cure or medication has been introduced so far; therefore, researchers still investigate potential drugs for treating ASD. One of the new medications introduced for this purpose is bumetanide...

BACKGROUND: Autism is a multifactorial disease with multiple etiologic hypotheses. Some studies suggest changes in brain GABA mediated inhibition in autism, and a higher intracellular chlorine levels in autistic children. Given these data, clinical trials are conducted to test the efficacy of diuretics in improving clinical symptoms in autism. AIM: The aim of our study was to evaluate the effectiveness of Bumetanide in autistic children. METHODS: This is an experimental study of cross-type...

An important detail was omitted in the Method of the original Article, I.E, The CARS and other evaluations were conducted 'blind' to condition (Bumetanide or no treatment) by experienced clinicians. This has now been updated in the HTML and PDF versions of this Article.

Bumetanide has been reported to alter synaptic excitation-inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up...

RATIONALE: Autism spectrum disorder (ASD) is a common neurodevelopmental disorder caused by complex interactions between genetic and environmental factors. Recent studies suggest that Vitamin D3 or bumetanide therapy may improve the core symptoms of ASD in some individuals. However, there are no guidelines that provide clinicians with evidence-based treatment regimens for the use of these therapies in ASD. PATIENT CONCERNS: A 30-month-old female was referred to our department because she did not respond when her name was called...

Autism spectrum disorder (ASD) appears in early childhood and is characterized by persistent deficits in communication and social interaction, as well as restricted interests, repetitive behaviors, and unusual sensory issues. ASD can be idiopathic or syndromic, in the latter case representing one of the many manifestations of a genetic disorder, such as Rett syndrome. Psychopharmacology cannot directly ameliorate core autistic symptoms, but rather aims at treating comorbid disorders, such as ADHD, sleep disturbances, psychomotor agitation and aggressiveness, seizures, and anxiety...

Autism spectrum disorders (ASD) are neurodevelopmental disorders induced by genetic and environmental factors. In our recent studies, we showed that the GABA developmental shifts during delivery and the second postnatal week are abolished in two rodent models of ASD. Maternal treatment around birth with bumetanide restored the GABA developmental sequence and attenuated the autism pathogenesis in offspring. Clinical trials conducted in parallel confirmed the usefulness of bumetanide treatment to attenuate the symptoms in children with ASD...

Introduction : Autism spectrum disorder (ASD) defines impairments in a broad range of behaviors in two domains, social communication and repetitive behaviors and/or restricted interests. Drug discovery is ongoing for ASD, but no drugs have been approved for the core behaviors. Animal models are invaluable for drug discovery, but are limited by the face, construct, and predictive validity for ASD. The genetic construct validity of animal models has provided potential targets including biological events early in development which are indeed challenging to treat pharmacologically...

Bumetanide (BTN or BUM) is a FDA-approved potent loop diuretic (LD) that acts by antagonizing sodium-potassium-chloride (Na-K-Cl) cotransporters, NKCC1 (SLc12a2) and NKCC2. While NKCC1 is expressed both in the CNS and in systemic organs, NKCC2 is kidney-specific. The off-label use of BTN to modulate neuronal transmembrane Cl- gradients by blocking NKCC1 in the CNS has now been tested as an anti-seizure agent and as an intervention for neurological disorders in pre-clinical studies with varying results. BTN safety and efficacy for its off-label use has also been tested in several clinical trials for neonates, children, adolescents, and adults...

We report that the apical dendrites of CA3 hippocampal pyramidal neurons are increased during labor and birth in the valproate model of autism but not in control animals. Using the iDISCO clearing method, we show that hippocampal, especially CA3 region, and neocortical volumes are increased and that the cerebral volume distribution shifts from normal to lognormal in valproate-treated animals. Maternal administration during labor and birth of the NKCC1 chloride transporter antagonist bumetanide, which reduces [Cl- ]i levels and attenuates the severity of autism, abolished the neocortical and hippocampal volume changes and reduced the whole-brain volume in valproate-treated animals...

OBJECTIVE: To evaluate clinical trials using bumetanide in autism spectrum disorder (ASD) treatment. DATA SOURCES: PubMed and Ovid MEDLINE (1946 to October 2018) were searched using terms bumetanide and autism. Bibliographies were reviewed for other relevant trials. STUDY SELECTION AND DATA EXTRACTION: English language, randomized, controlled, clinical trials in humans were evaluated. Three trials met all inclusion criteria. DATA SYNTHESIS: Oral bumetanide was studied in 208 patients, 2 to 18 years old, with ASD...

Autism spectrum disorder is defined by two core symptoms: a deficit in social communication and the presence of repetitive behaviors and/or restricted interests. Currently, there is no US Food and Drug Administration-approved drug for these core symptoms. This article reviews the biological origins of the social function deficit associated with autism spectrum disorder and the drug therapies with the potential to treat this deficit. A review of the history of autism demonstrates that a deficit in social interaction has been the defining feature of the concept of autism from its conception...