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Title: Do novel gene therapies influence motor, social and thinking skills in young children with spinal muscular atrophy?
Supervisor: Michelle de Haan, Giovanni Baranello
Project Description:
Background and aims:
Spinal muscular atrophy is a genetic neuromuscular condition that creates life-impacting, major motor difficulties (e.g., difficulties swallowing, breathing, playing) that affect life expectancy and quality of life. Spinal muscular atrophy type 1 (SMA1) appears within the first 6 months; it is the most common and severe form wherein children do not achieve motor milestones such as sitting or walking. Historically, children with this type of SMA do not survive beyond their second birthdays. Fortunately, today, children are potentially able to live longer and have improved motor outcomes due to the development of novel disease-modifying and gene replacement therapies. However, the longer term neurodevelopmental, communication, and wellbeing outcomes of children with SMA1 who have been treated with these novel therapies are still largely unknown. Given the well-established contribution of motor skills to cognition and social skills in typical development, we aim to understand the motor, cognitive and social outcomes for treated SMA1 children. Our investigations will cover specific neuropsychological domains, including speech/language, social communication and interaction, spontaneous play, memory, and executive functions as well as neurophysiological measures (EEG) of cognitive ability that are relatively independent of motor or speech difficulties. We will compare children who received different forms of treatment, and will consider the role of different variables, including disease severity, age at diagnosis and treatment initiation, disease duration before treatment, number of SMN2 gene copies, and socio-cultural-environmental factors.
Methods:
Participants will be children diagnosed with SMA1 at Great Ormond Street Hospital, and healthy peers .
Measures will include a variety of standard neuropsychological measures and questionnaires, direct behavioural observations using standardised approaches, parent-child interaction and electroencephalography (EEG).
Project outcomes:
We aim to develop a gold standard protocol for developmental follow up to predict outcomes and evaluate treatments. From a theoretical point of view, the project will inform how motor development contributes to social and cognitive development. The student will receive the chance to acquire a diverse set of skills in neuropsychological assessment, EEG acquisition and analysis, video coding of parent-child interactions and applying these in children of a wide age range and ability levels.
Timeline:
Fall 2025: Training-assessments & library skills, finalising ethics approval; literature review
Jan 2026: Start of Data collection; start of systematic review.
March 2026: Submit systematic review for publication
March 2026: Complete MPhil/PhD upgrade
Jan 2028: Complete data collection and finalise analysis plan;
Feb-August 2028: data analysis; write up of thesis; identify examiners.
Fall 2028 Submit completed thesis
References:
1. Katus, L., Mason, L…..de Haan, M. and the BRIGHT team (2020). ERP markers are associated with neurodevelopmental outcomes in 1-5 month old infants in rural Africa and the UK. Neuroimage, 210:116591. doi: 10.1016/j.neuroimage.2020.116591.
2.Masson, R, Brusa, C., Scoto, M., Baranello, G. (2021) Brain, cognition, and language development in spinal muscular atrophy type 1: a scoping review. Dev Med Child Neurol ;63(5):527-536. doi: 10.1111/dmcn.14798.
3.Servas, L., Baranello, G., et al. (2021). Therapeutic interventions for spinal muscular atrophy: preclinical and early clinical development opportunities Expert Opin Investig Drug30(5):519-527. doi: 10.1080/13543784.2021.1904889.
Contact Information:
Michelle de Haan