Research Project 1

Hugo W. Moser Res Inst Kennedy Krieger, Baltimore MD

Investigators

Abstract

PROJECT 1: TRIAL READINESS – PROJECT ABSTRACT The Neuronal Ceroid Lipofuscinoses (NCLs, Batten diseases) are rare, inherited, fatal lysosomal disorders of childhood onset. Although the thirteen NCLs each have a unique genetic etiology, they share in common a set of severe, progressive signs and symptoms: vision loss, epilepsy, dementia, and movement disorders, resulting in lifelong disability and shortened lifespan. CNS-directed enzyme replacement therapy was approved for the treatmnt of CLN2 disease n 2017, however, progress in advancing new interventions and launching rigorous clinical phase trials has slowed since that time. Effective and targeted therapies are lacking for the other 12 recognized NCL diseases. Fortunately, small- and large-molecule and several gene-targeted therapies are at various stages of preclinical development for multiple NCL diseases. The Batten Disease Clinical Research Consortium (BDCRC) proposes a multi-site, longitudinal study of the NCLs to promote trial readiness and decrease common rare disease roadblocks to therapeutic translation: lack of comprehensive natural history data and lack of patient-centered, responsive outcome measures. This represents the first multi-site natural history collaboration for the NCLs in the United States. The study is open to all individuals with neuronal ceroid lipofuscinosis; initial analyses will target higher prevalence disease forms: CLN1, CLN2, CLN3, and CLN6 diseases. We will model the natural history of disease progression, focused on key disease events, loss of functional milestones, and application of disease-specific rating scales. We will also use novel digital technologies to evaluate gait, speech, and language functions in the clinic and in the home. Using a caregiver-centered approach, we will develop, conduct initial validity testing, and pilot a new NCL severity observer-reported outcome measure. In concert with the natural history study, participants will contribute biospecimens, linked to deep phenotypic data, to establish a national NCL biorepository. In accomplishing these aims, the BDCRC will fill critical gaps in NCL clinical knowledge, including development of robust and responsive outcome measures, and create resources to support rigorous design in future clinical trials, significantly improving readiness for testing novel therapeutics, ultimately leading to better treatments and improved outcomes for those living with NCL.