Metabolism-based therapies for epilepsy: new directions for future cures.
Mackenzie C. Cervenka,Juan M. Pascual,Jong M. Rho,Elizabeth A. Thiele,Gary Yellen,Vicky Whittemore,Adam L. Hartman +6 more
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TLDR
In this paper, the state of the science in metabolism-based therapies for epilepsy across the research lifecycle from basic to translational to clinical studies is considered, and a conceptual framework for creative, rigorous, and transparent research to benefit people with epilepsy through the understanding and modification of metabolism.Abstract:
OBJECTIVE Thousands of years after dietary therapy was proposed to treat seizures, how alterations in metabolism relates to epilepsy remains unclear, and metabolism-based therapies are not always effective. METHODS We consider the state of the science in metabolism-based therapies for epilepsy across the research lifecycle from basic to translational to clinical studies. RESULTS This analysis creates a conceptual framework for creative, rigorous, and transparent research to benefit people with epilepsy through the understanding and modification of metabolism. INTERPRETATION Despite intensive past efforts to evaluate metabolism-based therapies for epilepsy, distinct ways of framing a problem offer the chance to engage different mindsets and new (or newly applied) technologies. A comprehensive, creative, and inclusive problem-directed research agenda is needed, with a renewed and stringent adherence to rigor and transparency across all levels of investigation.read more
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DEPDC5-dependent mTORC1 signaling mechanisms are critical for the anti-seizure effects of acute fasting
Christopher J. Yuskaitis,Jinita B Modasia,Sandra Schrötter,Leigh-Ana Rossitto,Karenna J. Groff,Christopher Morici,Divakar S. Mithal,Ram Prosad Chakrabarty,Navdeep S. Chandel,Brendan D. Manning,Mustafa Sahin +10 more
TL;DR: In this paper , the brain mTORC1 signaling is reduced after acute fasting of mice and that neuronal mTORc1 integrates GATOR1 complex-mediated amino acid and tuberous sclerosis complex (TSC)-mediated growth factor signaling.
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Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link.
TL;DR: In this paper, the authors review the mechanisms by which sleep deprivation induces neuroinflammation and propose that neuroinflammations synergizes with seizure activity to worsen neurodegeneration in the epileptic brain.
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Caloric Restriction Mimetic 2-Deoxyglucose Reduces Inflammatory Signaling in Human Astrocytes: Implications for Therapeutic Strategies Targeting Neurodegenerative Diseases
K. Vallee,Jerel Adam Fields +1 more
TL;DR: Data suggest that inhibiting glycolysis in human astrocytes reduces IL-1β-induced reactivity, which may lead to novel therapeutic strategies to limit inflammation and enhance bioenergetics toward the goal of preventing and treating neurodegenerative diseases.
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Identification of Glucose Transport Modulators In Vitro and Method for Their Deep Learning Neural Network Behavioral Evaluation in Glucose Transporter 1–Deficient Mice
Gauri Kathote,Qian Ma,Gustavo Angulo,Hong Chen,Vikram Jakkamsetti,Aksharkumar Dobariya,Levi B. Good,Bruce A. Posner,Jason Y. Park,Juan M. Pascual +9 more
TL;DR: In this article , a gait testing platform for deep learning neural network analysis of drug impact on Glut1-deficient mouse locomotion is presented. But, the method is limited to a G1D mouse model that replicates the ataxia and other manifestations cardinal to the human disorder.
Journal ArticleDOI
Maximum dose, safety, tolerability and ketonemia after triheptanoin in glucose transporter type 1 deficiency (G1D)
I. Malaga,Adrian Avila,Sharon Primeaux,Raja Reddy Kallem,Charles R. Roe,William C. Putnam,Jason Y. Park,Shlomo Shinnar,Chul-Woo Ahn,Juan M. Pascual +9 more
TL;DR: In this paper , a 3 + 3 dose-finding approach was used to establish a maximum, potentially greater dose of triheptanoin for Glucose transporter type 1 deficiency encephalopathy (G1D).
References
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Ketogenic Diet for the Treatment and Prevention of Dementia: A Review:
TL;DR: The ketogenic diet has shown promise in regard to delay or mitigation of symptoms of cognitive decline and the renewed emphasis on neuroinflammation as a pathogenic contributor to cognitive decline, and the decreased systemic inflammation observed with theketogenic diet, it is plausible that this diet may delay, ameliorate, or prevent progression of Cognitive decline.
Journal ArticleDOI
The relationship between d‐beta‐hydroxybutyrate blood concentrations and seizure control in children treated with the ketogenic diet for medically intractable epilepsy
Jeffrey Buchhalter,Jeffrey Buchhalter,Sabrina D'Alfonso,Mary B. Connolly,Ernest Fung,Aspasia Michoulas,David S. Sinasac,Rachel Singer,Jacklyn Smith,Narender Singh,Jong M. Rho +10 more
TL;DR: This study was performed to clarify the relationship between seizure control and the most commonly measured metabolite of the ketone body d‐beta‐hydroxybutyrate, because specific ketone bodies may be useful as biomarkers of diet efficacy.
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Ketogenic Diets as an Adjuvant Therapy for Glioblastoma (KEATING): A Randomized, Mixed Methods, Feasibility Study
Kirsty J Martin-McGill,Kirsty J Martin-McGill,Anthony G Marson,Anthony G Marson,Catrin Tudur Smith,Bridget Young,Samantha J Mills,M. Gemma Cherry,M. Gemma Cherry,Michael D. Jenkinson,Michael D. Jenkinson +10 more
TL;DR: Recruitment to a KD trial for patients with GBM is possible; a six-week intervention period is proposed for a phase III trial and improvements to optimize future phase III trials are recommended.
Journal ArticleDOI
Epilepsy in inherited metabolic disorders.
TL;DR: It is expected that in a few years' time it will be possible to know the metabolomic profile of these diseases (possibly by non-invasive methods), thus facilitating accurate diagnosis and making it possible to establish the response to treatment and to identify all individuals who are carriers or remain minimally symptomatic in terms of their risk of manifesting or transmitting epilepsy.
Journal ArticleDOI
Can we predict a favourable response to Ketogenic Diet Therapies for drug-resistant epilepsy?
Natasha E. Schoeler,J. Helen Cross,Josemir W. Sander,Josemir W. Sander,Sanjay M. Sisodiya,Sanjay M. Sisodiya +5 more
TL;DR: No strong evidence that there are any specific factors that affect response to Ketogenic Dietary Therapies is found; gender and intellectual status do not seem to affect response; evidence is inconsistent for all other factors.
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