Understanding the Patient Journey, Current Treatment Approaches and Emerging Therapeutic Opportunities in CLN2 Batten Disease

Background CLN2 disease, Neuronal Ceroid Lipofuscinosis (NCL) type 2, is a rare, genetic neurodegenerative condition predominantly affecting children. CLN2 disease is characterized by seizures, language and motor decline, vision loss, and premature death. Currently, the only regulatory-approved 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 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 BDSRA Foundation and international partner patient advocacy organisations via email 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, unmet needs, and knowledge of and attitudes toward emerging therapeutic approaches, particularly gene-based therapies. Results Ninety-eight respondents from 19 countries completed the survey. 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 factors influencing decision-making 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=44/76). Conclusion While ERT has altered the treatment landscape for CLN2 disease, this survey highlights the ongoing disease burden and treatment challenges experienced by families. Findings demonstrate strong community interest in next-generation therapies that may reduce treatment burden and provide more comprehensive disease modification, including effects on both central nervous system (CNS) and ocular manifestations.