Speech development in spinal muscular atrophy after disease-modifying therapies

PROJECT SUMMARY Spinal Muscular Atrophy (SMA) is a rare neurodegenerative disorder characterized by progressive muscle weakness and atrophy due to degeneration of lower motor neurons. Historically, SMA was the leading genetic cause of infant mortality, with the majority of those who survived past infancy relying on mechanical ventilation and alternative nutritional support to live beyond age 2 years. Since 2016, however, FDA approved disease-modifying therapies have altered the disease’s trajectory, enabling the acquisition of motor milestones, reducing the need for ventilatory support, and allowing full oral nutrition. Despite these advances, the impact of disease modifying therapies on speech, language, and cognition has yet to be empirically quantified. This proposed project seeks to address this gap by examining speech, language, and cognitive development in children with SMA who have received these therapies. The aims of this study are as follows: Aim 1: To characterize speech motor abilities in children with SMA following disease-modifying therapy. We will collect behavioral speech data from 20 participants with SMA who have received disease-modifying therapy, aged 2 to 21 years, from a regional SMA clinic. From these data we will: (A) quantify performance of individuals with SMA after disease-modifying therapies compared to typically-developing expectations on the following variables: speech intelligibility, articulation rate, standardized articulation scores, maximum mouth opening, profile of speech subsystem involvement, and parent reported intelligibility in context; and (B) identify differences across these same variables among individuals, based on whether treatment was initiated pre- or post-symptomatically, and the age of treatment initiation. Aim 2: To characterize language and cognitive development in children with SMA following disease-modifying therapy. Using the children with SMA from Aim 1, we will: (A) quantify performance compared to typically-developing expectations on the following variables: receptive language, expressive language, and cognitive ability, as measured by standardized test scores and language sample analyses, and (B) identify differences across these same variables among individuals based on age at treatment initiation and symptom onset. This research is a critical first step for developing a comprehensive understanding of communication development, informing targeted speech interventions, and maximizing communicative participation for a new generation of children with SMA. The proposed project is a foundational first step to my long-term goal to advance the development of evidence-based speech and communication treatment for SMA to maximize participation and quality of life. This project, bolstered by extraordinary support from the University of Wisconsin-Madison, will provide extensive training in SMA, bulbar function, research design and analysis, ethical research practices, scientific writing, and professional development. This comprehensive training will position me to make meaningful contributions to the field of communication sciences and disorders and to serve the SMA community as an academic researcher.