Principal Investigator Prof. Louise Gallagher
Research Title: “Identification of quantitative EEG parameters for prognosis and severity rating in neurodevelopmental disorders.”
Meath Foundation Research Funding Awarded 2019
There were accessible and measurable markers that could help diagnosis, prognosis and treatment in Rett Syndrome and other Disorders of Brain Development, Dr. Daniela Tropea, Associate Professor of Molecular Psychiatry Trinity College Dublin, told the Conference.
She said a systematic study in a large number of patients would reveal more biomarkers for patients’ stratification and for measuring the efficacy of candidate treatments.
She was speaking on “Identification of quantitative EEG parameters for prognosis and severity rating in neurodevelopmental disorders.”
Prof. Tropea, who was the Lead Researcher on the project works with Prof. Louise Gallagher, Consultant Child and Adolescent Psychiatrist, who was awarded Meath Foundation research funding for the work.
Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by motor and communication deficits, cardio-respiratory dysfunction, problems with bone formation, seizures, anxiety, stereotypies. Retts Syndrome is caused by mutation in X-linked MECP2 encoding methyl CpG- binding protein 2.
Prof. Tropea said it was a rare condition, with a variability of symptoms. Clinical presentation was not always overlapping with genetic mutation. There was a general correlation of milder presentation with mutations in the C-Terminal region.
New candidate treatments were continuously proposed and tested, gene therapy was becoming a reality and it was important to use the lessons that had been learned.
In March 2023, the FDA had approved Trofinetide, the first drug approved for Rett’s Syndrome. Dr Tropea pioneered the studies of this class of compounds for the treatment of neurodevelopmental disorders, and she remarked, “We are very keen to use these compounds, but it is important to identify measurable parameters that can predict which patients would respond to the drug.”
She said there were challenges in clinical trials for rare disorders, problems measuring the efficacy of a drug (how did we measure the severity of the condition? what symptom did we look at?), different response to a drug (could we improve the selection of patients for the trials), the rarity of the condition/variability of the symptoms and different response to the drug (could we improve the selection of patients for the trials and the measurement of drug efficacy).
Looking at biomarkers of cortical activity, she said quantitative EEG revealed different coordination in brain activity in patients with different clinical presentations.
Coordination of cortical activity was dependent on the cortical area. Cortical activity was different in patients with resistance to AED. Quantitative analysis revealed differences across brain areas.
They had carried out the research project to establish if it was possible to use quantitative EEG to predict which patients would respond to treatment.
“Based on the score of the International Severity Scale (ISS) we divided the patients in two groups, and we measured cortical activity before and after the treatment. We divided patients into two groups – those who responded to treatment (Responders) and patients who did not respond to treatment (Non Responders). We found that the patterns of cortical activity were different in patients that responded and those who did not respond to treatment. Our pilot study showed that the quantification of brain activity combined with machine learning revealed in advance which patients would respond to treatment.
“The way to understand and defeat Rare Disorders is by joining forces. We need to increase the number of patients in our research and to coordinate the efforts with other countries. To this aim we created DATARETT: a data platform for clinical and research data currently set up in Ireland for the collection of data of Irish patients with RTT. We plan to expand it to include several data type and multiple members in different countries. We also plan to expand the platform to other rare neurodevelopmental disorders.”
Prof. Tropea said she would like to thank Prof. Louise Gallagher, Stefania Bellini, Ines Molinos, Nial Mortimer, Conor Keogh, Adam Dyer, Stephen Shovlin, Albert Sanfeliu, Snow Back, Ciara Campbell, Komal Zade the Rett Families and the Clinical personnel involved in the work.