Mos-FED (Mosaicism in Focal Epilepsy Cortical Dysplasia Tissue)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Blood and nasal swab sampling.
- Who it may be relevant to
- Registry conditions: Focal Cortical Dysplasia, Epilepsy. Basic parameters: No limits · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United Kingdom
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Dissecting mTOR Pathway Mosaicism in FCDII-Harbouring Epileptic Brain and Peripheral Tissue.
Overview
Focal cortical dysplasia (FCD) is a malformation of brain development, the most common cause of drug-resistant epilepsy and often caused by mutations in mammalian target of rapamycin (mTOR) pathway genes. Patients with FCD develop drug-resistant seizures. This study will look at FCD tissue removed during epilepsy surgery and aims to detect mutations in mTOR pathway genes in brain cells. Secondly, the investigators will establish if evidence of mutations found in brain cells can also be detected as circulating free DNA (cfDNA) in blood. By looking at which genes are made into proteins in individual cells found in epilepsy surgical tissue (single cell expression profiling),the investigators will attempt to identify new genetic targets in FCD. The main outcome will be finding new causes of epilepsy with FCD and the development of new diagnostic and screening tools.
Detailed description
Primary Objectives:
1. To identify if somatic mosaicism for mTOR is present in resected tissue from patients with FCDIIA/B, and can be detected in DNA from patient's serum as circulating free DNA (cfDNA) or from nasal epithelial cells collected non-invasively by olfactory mucosal brush swab. 2. To establish if single cell expression profiling from resected fresh frozen tissue reveals novel FCD causing pathways and single cell RNA sequencing increases the yield of mTOR pathway variant detection. 3. To determine if phosphorylated upstream and downstream mTOR pathway components can be characterised by immunohistochemistry and Western blot as novel biomarkers of mTOR activation in human FCDII tissue.
Secondary Objectives:
To engage with patients, representatives and charitable organisations to assess feasibility and develop plan to set up a future trial of mTOR inhibitor treatment.
Interventions
- Genetic Blood and nasal swab sampling
Genetic screening of DNA samples (blood, mucosal swab, brain tissue) from 60-100 patients with histologically confirmed diagnosis of FCDIIA/B identified from Epilepsy Surgery Databases.
Primary outcome measures
- somatic mosaicism [Time frame: 2 years]
- single cell expression profiling [Time frame: 2 years]
- phosphorylated targets [Time frame: 2 years]
Eligibility criteria
Epilepsy in Focal Cortical Dysplasia Type IIA/B
Inclusion criteria
- Adult and Paediatric Patients (male and female)
- A histologically proven diagnosis of FCDIIA/B or a suspected diagnosis of FCDIIA/B (on MRI/EEG and PET grounds) awaiting resective Epilepsy surgery.
- Able to attend appointment/hospital and undergo sampling of serum and nasal swab
- Informed Consent Available
Exclusion criteria
- Any acute or chronic conditions that could limit the ability of the patient to participate in the study.
- Refusal to give informed consent.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Diagnostic
Study locations
United Kingdom · 1 center
- King's College Hospital — London
Identifiers
NCT: NCT06053671 · 303113_28022022 · 22/WA/0326