1. University of Rochester Batten Center:
Research Program in JNCL: Creation of a Patient Registry and Collaboration with Patient Advocates
JW Mink, EA de Blieck, EF Augustine, FJ Marshall, HR Adams, J Cialone, JM Kwon, A Thatcher, N Newhouse, A Vierhile and the Batten Study Group
INTRODUCTION
The University of Rochester Batten Center’s (URBC) mission is to find treatments to slow, halt, or prevent JNCL. To reach move toward this goal, the URBC has 1)
established a JNCL research cohort, 2) developed a clinical outcome measure, 3) validated a non-invasive diagnostic sampling method, and 4) designed and
implemented a clinical trial in JNCL.
Objective 1 - Batten Disease Registry
Points of Interest
•237 registrants from 198 families
•149 with JNCL (CLN3 disease)
•120 children from 99 families have participated in the
UBDRS study
•To date, seven participants have been recruited and
enrolled in the ongoing clinical trial via the registry
Quantitative, Natural History Studies of JNCL with the UBDRS
• Multi-domain, clinical rating scale
▪ Obtained at annual BDSRA meetings in a mobile research setting
• Used for natural history studies and clinical trials
• Validated telemedicine use of scale
Figure 2. UBDRS Subjects by Year and Setting
Objective 2 - Unified Batten Disease Rating Scale
UBDRS Accomplishments
•A total of 323 UBDRS exams have been completed on 120 children
•120 children evaluated annually, from 1 to 11 times each
•UBDRS reliability & validity established
•87 JNCL-affected children completed neurobehavioral studies. Of
these, 59 also completed the UBDRS, permitting direct comparison
•Disease burden and rate of progression was quantified in 82
subjects. This is the largest known cohort of JNCL-affected persons
that has been evaluated with a disease-specific rating scale
Objective 3 – Novel Diagnostic Methods
Points of Interest
•For those negative for the common deletion, the entire CLN3
coding region was subjected to Sanger nucleotide sequence
analysis
•Genetic confirmation obtained for all 120 UBDRS subjects
Develop Non-Invasive Diagnostic Sampling Method
•Buccal epithelial cell collection for genotyping (2004) – a non-
invasive, child friendly method (vs. venipuncture or biopsy)
•Developed and validated a rapid diagnostic testing
methodology for the most common CLN3 mutation (965 bp
deletion of exons 7 and 8)
• The registry and BDSRA collaboration enabled us to
implement multiple research protocols, to develop and
validate a rating scale, evaluate natural history of disease, and
and establish new methods for disease confirmation.
• This work highlights the preparatory natural history research
and infrastructure development needed to facilitate efficient
implementation of clinical trials in rare diseases.
Conclusions
This work was support by grants from the Batten Disease Support and Research Association, National Institute of Neurological Disorders and Stroke (R01NS060022, K12 NS066098, U54NS065768, K23
NS058756), Luke & Rachel Batten Foundation, and the Food and Drug Association Orphan Products Development (1 R01 FD003908-01). All work was conducted under URMC Research Subjects Review
Board-approved protocols. All parents provided consent for their child’s participation. We thank the BDSRA for their assistance, and especially thank all affected children and families for their
participation in this research.