Patient and Family Perspectives on Clinical Outcomes in Therapy Trials in Megalencephalic Leukoencephalopathy with...

To determine which clinical outcomes are most meaningful to patients with megalencephalic leukoencephalopathy with subcortical cysts (MLC) and their caregivers to enhance clinical trial readiness.

An online survey was developed by the MLC Clinical Expert Consortium and Alliance MLC. The survey, available in eight languages, was distributed via treating neurologists and Alliance MLC, and completed anonymously by patients and caregivers. It included open-ended questions on burdensome daily-life aspects, treatment priorities, and therapy expectations; responses were categorized into functional domains. The survey also included a ranking of key symptom domains. Responses were analyzed separately for caregiver- and patient-reported burden. Subgroup analyses were performed for age (<15 years vs. ≥15 years) and country of residence (Türkiye, India, and Italy).

Eighty-five surveys representing 83 patients were included. Motor dysfunction was most frequently reported as most burdensome for both caregivers (74%) and patients (58%), followed by communication and activities of daily living (ADL). Within the motor domain, ambulation was most frequently mentioned. Regarding the ranking, motor function scored highest in 69% of respondents. In patients ≥ 15 years, ambulation was less frequently mentioned, whereas ADL dependency was more frequently reported than in patients <15 years. Comparisons between countries revealed few differences. Hopes for therapy were mainly concerned with motor improvement and halting disease progression.

Motor function, particularly ambulation, is the most burdensome and prioritized domain for patients with MLC and their caregivers, regardless of age or country. Incorporating patient-centered priorities into future clinical trial design is essential to ensure that emerging therapies target meaningful improvements.