Laura Mantoan Ritter

I investigate novel diagnostic and therapeutic tools and precision treatments for super-refractory and genetic forms of epilepsy.

The first area of interest is the mechanistic target of rapamycin (mTOR) signalling pathway, which regulates fundamental cellular processes including growth control, autophagy and metabolism.

Hyperactivation of the mTOR pathway causes 14 diverse, rare, early-onset, hard-to-treat genetic diseases affecting 10,000 people in the UK. The symptoms range from brain malformations causing epilepsy to benign tumours in multiple organs.

With my co-investigators Prof Joseph Bateman and Prof Deb Pal at the Institute of Psychology, Psychiatry and Neurosciences, KCL, we are leading a National rare disease clinical and research node for mTOR pathway diseases, consisting of 12 national collaborating centres: we are establishing an mTOR diseases patient registry and tissue repository, patient-derived iPSC lines and will identify targets for genetic precision treatments. Using human surgical tissue from patients with focal cortical dysplasia (a brain malformation and one of the commonest causes of drug-resistant focal epilepsy), my group also investigates novel somatic mTOR pathway mutations by next generation sequencing. We are further developing novel genetic “liquid biopsy” tools for this group of patients.

The second focus of my research is New-onset refractory status epilepticus (NORSE). NORSE and its subcategory febrile infection-related epilepsy syndrome (FIRES) are rare, devastating clinical presentations, typically affecting previously healthy adults and children, with high case fatality, and long-term morbidity in survivors. Aetiology is not understood, resistance to anaesthetic and antiseizure drug therapy is a major hurdle and there is urgent need to develop new treatment approaches.

My translational research team brings outstanding clinicians and scientific collaborators together and is embedded within NORSE-UK, a UK-wide network of all tertiary Neuroscience Centres in the UK, which I founded and lead (with Dr Lina Nashef, Consultant Neurologist, King’s College Hospital). My group investigates novel diagnostic tools (metagenomic sequencing, astrovirus sequencing, cytokine assays, neuropathology) to understand the aetiology and pathophysiology of NORSE.

Through a current clinical trial we are addressing the question whether vagal nerve stimulation (VNS) in NORSE patients may confer benefits in aborting unremitting status epilepticus, modulate ictogenesis and reduce long-term chronic seizure burden.