Advanced Treatments for Childhood Epilepsy

Joshi, Sucheta M.; Singh, Rani K.; Shellhaas, Renée A.

doi:10.1001/jamapediatrics.2013.424

Cited by 13 publications

(7 citation statements)

References 71 publications

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“…SV2A −/− mice, on the other hand, exhibit early severe seizures and die within 2–3 weeks after birth (Kaminski et al, 2012). Other data from these transgenic mice demonstrated the role of SV2A in modulation of vesicular exocytosis (Xu and Bajjalieh, 2001; Budzinski et al, 2009; Chang and Sudhof, 2009; Wan et al, 2010; Yao et al, 2010; Joshi et al, 2013). Although LEV failed in classical seizure screening tests, this drug significantly inhibited the development of seizure kindling and displayed a potential antiepileptogenic effect in the chronic pilocarpine post-SE rat model (Kaminski et al, 2012).…”

Section: Introductionmentioning

confidence: 87%

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Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Liefferinge¹,

Massie²,

Portelli³

et al. 2013

Front. Cell. Neurosci.

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The vesicular neurotransmitter transporters (VNTs) are small proteins responsible for packing synaptic vesicles with neurotransmitters thereby determining the amount of neurotransmitter released per vesicle through fusion in both neurons and glial cells. Each transporter subtype was classically seen as a specific neuronal marker of the respective nerve cells containing that particular neurotransmitter or structurally related neurotransmitters. More recently, however, it has become apparent that common neurotransmitters can also act as co-transmitters, adding complexity to neurotransmitter release and suggesting intriguing roles for VNTs therein. We will first describe the current knowledge on vesicular glutamate transporters (VGLUT1/2/3), the vesicular excitatory amino acid transporter (VEAT), the vesicular nucleotide transporter (VNUT), vesicular monoamine transporters (VMAT1/2), the vesicular acetylcholine transporter (VAChT) and the vesicular γ-aminobutyric acid (GABA) transporter (VGAT) in the brain. We will focus on evidence regarding transgenic mice with disruptions in VNTs in different models of seizures and epilepsy. We will also describe the known alterations and reorganizations in the expression levels of these VNTs in rodent models for temporal lobe epilepsy (TLE) and in human tissue resected for epilepsy surgery. Finally, we will discuss perspectives on opportunities and challenges for VNTs as targets for possible future epilepsy therapies.

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Section: Introductionmentioning

confidence: 87%

“…The ketogenic diet is often used to control epilepsy (Joshi et al, 2013). Although fasting does not affect the activity of glutamate reuptake transporters (Bough et al, 2007), the vesicular transporters are possibly targeted by the ketone bodies, in particular acetoacetate and β-hydroxybutyrate, produced by this diet.…”

Section: Vglutsmentioning

confidence: 99%

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Liefferinge¹,

Massie²,

Portelli³

et al. 2013

Front. Cell. Neurosci.

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“…2 Up to 30% of children with epilepsy continue to have seizures while on anti-seizure medication, a condition known as drug-resistant epilepsy (DRE). Novel neurotechnologies, including minimally invasive and neuromodulatory options for seizure control, represent a new frontier for improving the subjective and objective quality of life for pediatric DRE patients, 3 but best practices for treatment do not currently exist. Properly selected, up to 70% of DRE patients can become seizure-free after surgery.…”

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confidence: 99%

The Clinical Research Landscape of Pediatric Drug-Resistant Epilepsy

et al. 2020

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Objective: To characterize the clinical research landscape of pediatric drug-resistant epilepsy (DRE) with a focus on neurotechnology. Method: We searched the ClinicalTrials.gov registry using the terms “epilepsy” and “drug resistant” for studies including participants age 0-17 years. Returns were grouped by intervention (eg, neurotechnological, drug). Key trial features such as age range, trial status and outcomes were compared across interventions. Results: We identified 101 registered trials with pediatric DRE patients. Thirty-two (32%) investigate neurotechnological interventions, devices, or diagnostic procedures; 13 (41%) are currently active. Among neurotechnology trials, 15 (46%) investigate vagus nerve stimulation, transcranial direct current stimulation, or deep brain stimulation; few are specific to children. Of the remaining 69 trials, 37 investigate a drug, 17 investigate a dietary therapy, and 15 investigate another intervention. Seizure frequency is the most frequent primary outcome measured in the trials identified. Significance: The landscape of registered trials pertaining to pediatric DRE reflects a lag between clinical research and clinical practice, and highlights the need for timely evidence before novel neurotechnological interventions are widely adopted into clinical practice.

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“…The oligonucleotide is delivered intrathecally through lumbar puncture, providing a more focused CNS delivery. Such an approach, while still invasive, could be used for microRNA‐based therapies in epilepsy, for example as an intermediate therapeutic intervention in the case when currently available drugs fail, before performing surgery or in cases where surgery is not indicated (Joshi et al, ).…”

Section: Conclusion and Future Challenges For Clinical Developmentmentioning

confidence: 99%

MicroRNA‐induced silencing in epilepsy: Opportunities and challenges for clinical application

Tiwari

Peariso

Groß

2017

Developmental Dynamics

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MicroRNAs are master regulators of gene expression. Single microRNAs influence multiple proteins within diverse molecular pathways and networks. Therefore, changes in levels or activity of microRNAs can have profound effects on cellular function. This makes dysregulated microRNA-induced silencing an attractive potential disease mechanism in complex disorders like epilepsy, where numerous cellular pathways and processes are affected simultaneously. Indeed, several years of research in rodent models have provided strong evidence that acute or recurrent seizures change microRNA expression and function. Moreover, altered microRNA expression has been observed in brain and blood from patients with various epilepsy disorders, such as tuberous sclerosis. MicroRNAs can be easily manipulated using sense or antisense oligonucleotides, opening up opportunities for therapeutic intervention. Here, we summarize studies using these techniques to identify microRNAs that modulate seizure susceptibility, describe protein targets mediating some of these effects, and discuss cellular pathways, for example neuroinflammation, that are controlled by epilepsy-associated microRNAs. We critically assess current gaps in knowledge regarding target-and cell-specificity of microRNAs that have to be addressed before clinical application as therapeutic targets or biomarkers. The recent progress in understanding microRNA function in epilepsy has generated strong momentum to encourage in-depth mechanistic studies to develop microRNA-targeted therapies. Developmental Dynamics 247:94-110, 2018. V C 2017 Wiley Periodicals, Inc.

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Advanced Treatments for Childhood Epilepsy

Cited by 13 publications

References 71 publications

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?

The Clinical Research Landscape of Pediatric Drug-Resistant Epilepsy

MicroRNA‐induced silencing in epilepsy: Opportunities and challenges for clinical application

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