Nucleotide Protein -3 in Epileptic Children

Biochemical Role of Nucleotide Protein -3 That Activate the Interleukin-1B in Epileptic Children

Epilepsy is one of common serious neurological malfunction, characterized by recurrent unprovoked seizures. It always accompanied with multitude of complications as cognitive, behavioral, and psychiatric disorders.

Experimental studies and clinical evidence obtained in animal models of epilepsy and human brain specimen from various drug-resistant forms of epilepsy show the activation of the innate and adaptive immunity mechanisms and the induction of the associated inflammatory processes in the epileptogenic foci.

Study Overview

• Status: Unknown
• Conditions: Epilepsy in Children
• Intervention / Treatment: Diagnostic test: Expression of nucleotide protein -3

Detailed Description

Epilepsy affects approximately 1% of the world population. Lifetime prevalence of childhood and adolescence epilepsy (children <18 years) in Upper Egypt was 9.7/1000, with higher prevalence among children <12 years (10.8/1000).

There is a clear cause for epilepsy in only a minority of the cases, while in up to70% of all case of epilepsy in adults and children, no cause can be discovered. Some of the main causes of epilepsy include: Low oxygen during birth, head injuries that occur during birth or from accidents during youth or adulthood, brain tumors, infections such as meningitis or encephalitis, stroke or any other type of damage to the brain.

A role of inflammatory molecules in the generation of seizures had been first investigated when selected anti-inflammatory treatments, in particular, steroids, immuno-globulins, and adrenocorticotropic hormone (ACTH), were shown to control seizures in pediatric epilepsies refractory to conventional anticonvulsive drugs. In addition, specific epileptic disorders have been associated with the presence of neuronal antigen-directed antibodies in plasma or cerebrospinal fluid (CSF).

A nucleotide-binding oligomerization domains (NODs) are cytosolic proteins that include key regulators of apoptosis and pathogen resistance in mammals and plants. A large number of NODs contain leucine-rich repeats (LRRs), hence referred to as NOD-LRR proteins. The NLRP3 gene provides instructions for making a protein called cryopyrin. Cryopyrin is a member of a family of proteins called nucleotide-binding domain and leucine-rich repeat containing (NLR) proteins. NLR family have two common features: the first is a nucleotide-binding oligomerization domain which is bound by ribonucleotide-phosphates (rNTP) and is important for self-oligomerization. The second is a C-terminal leucine-rich repeat, which serves as a ligand-recognition domain for other receptors (e.g. Toll like receptor (TLR)) or microbial ligands, while NLRP3 has been identified in microglial cells.

• Study Type: Observational
• Enrollment (Anticipated): 80

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Epileptic children

Description

Inclusion Criteria:

• Epileptic children in Assiut university hospital, pediatric department, neurology unit.

Exclusion Criteria:

• Children with other chronic disease such as liver, kidney or heart disease
• patient who have apparent infection

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
epileptic children; fifty patient with epilepsy	Diagnostic test: Expression of nucleotide protein -3; Expression of nucleotide protein -3 will be measured in serum by ELISA
Healthy controls; thirty healthy control	Diagnostic test: Expression of nucleotide protein -3; Expression of nucleotide protein -3 will be measured in serum by ELISA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The mean difference of nucleotide protein -3 inflammatory marker expression in epileptic children and controls	better understanding the role of inflammation in pathogenesis of epilepsy in children	Baseline

Collaborators and Investigators

• Sponsor: Assiut University

Publications and helpful links

General Publications

• He Q, Jiang L, Man S, Wu L, Hu Y, Chen W. Curcumin Reduces Neuronal Loss and Inhibits the NLRP3 Inflammasome Activation in an Epileptic Rat Model. Curr Neurovasc Res. 2018;15(3):186-192. doi: 10.2174/1567202615666180731100224.
• Farghaly WM, Abd Elhamed MA, Hassan EM, Soliman WT, Yhia MA, Hamdy NA. Prevalence of childhood and adolescence epilepsy in Upper Egypt (desert areas). Egypt J Neurol Psychiatr Neurosurg. 2018;54(1):34. doi: 10.1186/s41983-018-0032-0. Epub 2018 Nov 9.
• Xu D, Miller SD, Koh S. Immune mechanisms in epileptogenesis. Front Cell Neurosci. 2013 Nov 8;7:195. doi: 10.3389/fncel.2013.00195. eCollection 2013.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2020
• Primary Completion (Anticipated): November 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: January 3, 2020
• First Submitted That Met QC Criteria: January 3, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 6, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Epilepsy; Children; NLRP3; Interleukin B1; Nuclear Factor-Kappa B
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy
• Other Study ID Numbers: Epilepsy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No