Clinical trial NCT05096871: Association of Brain Derived Neurotrophic Factor (BDNF) rs6265 Gene Polymorphism With Susceptibility to Epilepsy
Official title: Association of Brain Derived Neurotrophic Factor (BDNF) rs6265 Gene Polymorphism With Susceptibility to Epilepsy
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Epilepsy
Keywords: BDNF in epileptic patients
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2021-10-27
Enrollment: 90
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with epilepsy aged from 1 year to less than 15 years, in Pediatric department of Sohag University Hospital and healthy control children of matched age and sex

Brief summary: Epilepsy is a common neurological condition that affects people of all ages.Recent studies found that epilepsy is associated with several chromosomal regions, where mutations in these regions cause neurological dysfunction.

BDNF which is the most ample neurotropic factor in the CNS, has survival and growth promoting roles in a variety of neurons. It has been shown to promote excitatory (glutamatergic) synapses while weakening inhibitory (GABAergic) ones.

A nonsynonymous G to A single-nucleotide polymorphism (SNP) exists at position 196 of exon 2 (rs6265), which results in valine (val) to methionine (met) substitution. This polymorphism affects intracellular packaging of pro-BDNF, its axonal transport and in turn, activity-dependent secretion of BDNF at the synapse.

Detailed description: Epilepsy was defined as the separate occurrence of two or more unprovoked seizures, manifested by involuntary motor, sensory, or autonomic, alone or in combination, and not diagnosed as neonatal or febrile seizures. Despite extensive studies, the molecular causes of the disease are not yet discovered completely. A functional imbalance between excitatory (transmitted by glutamate) and inhibitory signals (transmitted by γ-amino butyric acid or GABA) in neural cells has been regarded as a putative contributing factor in epilepsy.

The brain-derived neurotropic factor (BDNF) encodes a small dimeric protein which is the most ample neurotropic factor in the CNS.It has been shown to promote excitatory (glutamatergic) synapses while weakening inhibitory (GABAergic) ones.Any interference with the BDNF signaling pathway may negatively affect downstream neuronal functions and cause neuronal diseases.

A nonsynonymous G to A single-nucleotide polymorphism (SNP) exists at position 196 of exon 2 (rs6265), which results in valine (val) to methionine (met) substitution at codon 66 (val66met), changing the 5' proregion of the human BDNF protein. This polymorphism affects intracellular packaging of pro-BDNF, its axonal transport and in turn, activity-dependent secretion of BDNF at the synapse

Eligibility criteria: Inclusion Criteria:

• Epileptic patients aged more than 1 year and less than 15 year who recently had seizures over a period of one year

Exclusion Criteria:

* Patients \> 15 years old or less than 1 year.
* Patients that have epilepsy as a result of head injuries, brain tumors , exposure to low oxygen during birth or infections such as meningitis or encephalitis .
* Patients that have no sufficient medical records or unreliable seizure frequency,
* patients with developmental disorders such as Autism and Neurofibromatosis

Primary outcomes:
measure: Iinvestigate the possible association between BDNF rs6265 polymorphism and epilepsy susceptibility in Egyptian patients
timeFrame: within 3 days after collection of samples
Secondary outcomes:
measure: Assess the utility of serum BDNF concentration as a diagnostic tool for Epilepsy and evaluate its relationship with disease severity
timeFrame: within 3 days after collection of samples
Other outcomes:
Locations:
Study officials:
References:
citation: Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR. The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell. 2003 Jan 24;112(2):257-69. doi: 10.1016/s0092-8674(03)00035-7.
citation: Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci. 2004 May 5;24(18):4401-11. doi: 10.1523/JNEUROSCI.0348-04.2004.
citation: Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, Engel J Jr, Forsgren L, French JA, Glynn M, Hesdorffer DC, Lee BI, Mathern GW, Moshe SL, Perucca E, Scheffer IE, Tomson T, Watanabe M, Wiebe S. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014 Apr;55(4):475-82. doi: 10.1111/epi.12550. Epub 2014 Apr 14.
citation: Loscher W, Potschka H, Sisodiya SM, Vezzani A. Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options. Pharmacol Rev. 2020 Jul;72(3):606-638. doi: 10.1124/pr.120.019539.