Mos-FED (Mosaicism in Focal Epilepsy Cortical Dysplasia Tissue) (MosFED)

King's College Hospital NHS Trust

Status: Enrolling

Conditions: Epilepsy; Focal Cortical Dysplasia

Treatments: Genetic: Blood and nasal swab sampling

Study type: Interventional

Funder types: Other

Identifiers

NCT06053671

22/WA/0326 (Other Identifier)

303113_28022022

Details and patient eligibility

About

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.

Full 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.

Enrollment: 60 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Epilepsy in Focal Cortical Dysplasia Type IIA/B

Key Inclusion Criteria:

1. Adult and Paediatric Patients (male and female)

2. A histologically proven diagnosis of FCDIIA/B or a suspected diagnosis of FCDIIA/B (on MRI/EEG and PET grounds) awaiting resective Epilepsy surgery.

3. Able to attend appointment/hospital and undergo sampling of serum and nasal swab

4. Informed Consent Available

   Key Exclusion Criteria:

5. Any acute or chronic conditions that could limit the ability of the patient to participate in the study.

6. Refusal to give informed consent.

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Patients with histologically confirmed FCDIIA/B undergoing or post Epilepsy Surgery

Experimental group

Description:

Genetic screening of DNA samples (blood, mucosal swab, brain tissue)

Treatment:

Genetic: Blood and nasal swab sampling