Abstract / Summary
Background CLN2 disease, Neuronal Ceroid Lipofuscinosis (NCL) type 2, is a rare, genetic neurodegenerative condition predominantly affecting children and characterized by seizures, progressive language and motor decline, vision loss, and premature death. Currently, the only approved disease-modifying therapy is the enzyme replacement therapy (ERT) Cerliponase alfa, administered fortnightly via intracerebroventricular infusion as a lifelong treatment. While ERT has been shown to slow motor and language decline, it is not curative and does not fully address all aspects of disease progression, including retinal degeneration. To better understand the lived experience of affected families, and perspectives on current and emerging treatments, we conducted a community survey of parents and caregivers of individuals with CLN2 disease. Methods A 25-question anonymous, voluntary survey was distributed through the US-based Batten Disease Support, Research and Advocacy (BDSRA) Foundation, and its international partner patient advocacy organisations via email, e-newsletters and social media. Eligible participants included current and bereaved parents or primary caregivers of individuals with CLN2 disease, regardless of treatment history. The survey explored treatment experiences and burden, unmet needs, and knowledge of and attitudes toward emerging therapeutic approaches, particularly gene-targeted therapies. Thematic analysis was performed on free-text responses. Results Ninety-eight respondents from 19 countries completed the survey, with the majority of participants from the United States and other predominantly English-speaking countries. Fifty-seven respondents reported current or prior use of ERT, with 94.7% (n=54/57) actively receiving treatment at the time of survey. ERT was perceived to provide greatest benefit for motor function and seizure control; however, respondents reported substantial treatment burden (mean burden score 4.8/7, n=66). Despite treatment availability, 94.9% of respondents (n=75/79) indicated a need for alternative therapeutic options and 94.8% (73/77) expressed interest in learning more about gene therapy. Overall, 72.4% (n=55/76) reported they were likely or very likely to consider participation in an investigational gene therapy trial. Key considerations included potential safety risks (57.9%, n=44/76), preclinical safety and efficacy evidence (54.0%, n=41/76), and whether ERT discontinuation would be required to participate (54.0%, n=41/76). Thematic analysis of 293 free-text responses identified substantial emotional, psychosocial and family impact, alongside treatment burden and persistent unmet need, hope for transformative therapies, and faith and resilience as prominent themes. Conclusion Despite the clinical benefits of ERT, CLN2 disease continues to impose substantial disease, treatment, and caregiver burden. Families expressed strong interest in emerging gene-targeted therapies while identifying safety, efficacy, treatment burden, and preservation of function as important considerations. Together, these findings demonstrate an ongoing need for therapies that can further modify disease progression, more comprehensively address both central nervous system and ocular manifestations of CLN2 disease and reduce treatment burden for affected individuals and their families.