<p>The study of cognitive function in spinal muscular atrophy (SMA) is a newly emerging field, generating important questions about how the disease and its treatment may influence neurodevelopment over time. At <strong>Cure SMA 2025</strong>, several presentations focused on the cognitive implications of SMA, including a panel discussion with clinical and research experts convened to explore emerging evidence and the importance of incorporating cognitive screening into patient care.</p> <p><br></p> <p><em>Following these presentations, featured expert Julie A. Parsons, MD, was interviewed by </em>Conference Reporter <em>Associate Editor-in-Chief Mona Shah, PharmD. Clinical perspectives from Dr Parsons on these findings are presented here.</em></p>

At Cure SMA 2025, a panel discussion called “Uncovering Cognitive Implications in Spinal Muscular Atrophy: Research Gaps, Clinical Insights, and Future Directions” featured several talks that shared new insights into and data on neurocognition in SMA. This is a new area of research and data collection, so there is limited information available.

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During the first presentation from the panel discussion, Sarah Wright, DO, from the Children’s National Hospital in Washington, DC, reported on the results of a modified Delphi survey of pediatric SMA providers to better understand the cognitive and neurodevelopmental concerns that are present in children with SMA (abstract 51). Of the 40 providers who were sent the questionnaire, 27 responded from 21 institutions; respondents saw a median of 75 patients with SMA per year. The domains that were of greatest concern to providers were language and social-emotional development, followed by executive function and attention deficits. Providers thought that the SMN2 copy number and age at diagnosis were the most critical factors influencing cognition and neurodevelopment, while the timing of disease-modifying therapy was not felt to be as important.

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Dr Wright also presented a literature review of cognitive function in SMA, showing that patients who seem to be the most affected have 2 or less copies of the SMN gene and lower assessment scores. She noted that autism may also occur more frequently in patients with SMA than in the general population. The American Academy of Pediatrics (AAP) recommends screening for autism with the Ages and Stages Questionnaire (ASQ) at 14 and 18 months as a routine assessment during pediatric evaluations, and that should be done in our children with SMA as well. Dr Wright concluded that there is a need for longitudinal studies using validated instruments to assess patients with SMA, as well as more research on SMA pathophysiology to better understand the impact of SMN protein on the central nervous system (CNS).

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Eduardo Tizzano, MD, PhD, presented emerging evidence linking SMN2 copy number to CNS malformations in the brains of patients with SMA during his talk from the panel discussion. Dr Tizzano and colleagues are also trying to correlate the genotype of patients who have significant neurocognitive issues with their genetic backgrounds. Based on Dr Tizzano’s presentation, I thought that it was interesting that there appears to be some validity to the statement that diminished SMN protein really does have an effect on the CNS.

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Next in the panel discussion at Cure SMA 2025, Gretchen Weatherly, PhD, LP, presented the current limitations in assessing neurocognition in patients with SMA. She acknowledged that, while we do not yet have SMA-specific neurocognitive assessment tools, this should not prevent clinicians from using the tools that we do have. In Dr Weatherly’s view, the tools that we have are adequate to perform assessments of cognitive function. Listening to patients and asking them about things that are happening with their school, development, and language during each SMA visit is a good start to introducing the idea that neurocognition is a concern. A longstanding idea in the SMA community is that “children with SMA are really smart,” and this has resulted in a little bit of a resistance to assessments. However, I agree that neurocognitive challenges are a real concern, and assessments can be done even if they are not validated specifically for SMA.

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In addition to the panel discussion, Charalambos Demetriou, PhD, presented his research on the developmental expression of SMN in the brain in a mouse model of SMA, which was a really good setup to help understand why translational medicine is important. We still do not fully understand SMN function in the CNS, but it may be related to cell proliferation and neuronal growth. I think that Dr Demetriou’s experimental mouse model that mimics what is happening in the human experience, including disease modifications at different age and stage points, is really interesting research. This may help us understand the thought that you may be able to change the neurophysiology and neuropathology in the CNS with the use of disease-modifying therapy and increases in SMN protein levels.

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So, I think that we are in this interesting space right now with neurocognition in that we have concerns that there are issues regarding lower SMN2 copy numbers and theoretically lower levels of SMN proteins in patients with SMA. We need more research on SMA pathophysiology to help us understand the importance and significance of SMN protein in the CNS and additional longitudinal studies to increase awareness and identify more standardized tools to do the assessments. Going forward, it is really important to evaluate these children with SMA because, if we can intervene and change their outcomes, there is no reason they should be treated differently than patients without SMA.