PRE-CELL: Clinical and Novel Biomarker Measures of Disease Progression in a Lead-In-Observational Study for a Planned Phase 1 Trial of Genetically-Modified Mesenchymal Stem Cells Over-Expressing BDNF in Patients with Huntington’s Disease (S25.004)

Abstract

Objective: To describe baseline characteristics and longitudinal rate of change in multiple clinical, novel biomarker and structural MRI measures for a cohort of subjects with early-stage Huntington’s disease (HD). Background: There are no existing disease-modifying therapies for HD. Mesenchymal stem cells (MSCs) engineered to overexpress brain-derived neurotrophic factor (BDNF) is a proposed therapeutic for neuroprotection in HD. PRE-CELL is the lead-in study for a future planned Phase I trial of MSC/BDNF in HD. Design/Methods: Subjects with genetically-confirmed early-stage HD, without dementia, unstable psychiatric symptoms, contraindications to MRI or neurosurgery were assessed every 6 months for 12 - 24 months. A linear mixed effects model was used to analyze the repeated measures of selected outcome measures in the cohort. Results: Forty-two subjects have been screened and 32 enrolled (38[percnt] females, mean age of 52, range, 23 - 74). The estimated annual change rates for selected clinical measures include: UHDRS Total Functional Capacity score, -0.7884 (p-value < 0.0001); Independence Score, -6.2546 (p-value < 0.0001); Total Motor Score 9.1038 (p-value < 0.0001); HD-Quality of Life score, 17.089 (p-value = 0.0078), E-COG total score, 6.6312 (p-value = 0.0035). Rates of change in the HD Cognitive Assessment Battery will be presented. Biomarker analysis indicates a strong linear relationship between serum and CSF mutant Huntingtin protein levels (correlation of 0.87774, p-value <0.0001). Analysis of serum and CSF BDNF levels will be presented. Structural MRI analysis shows significant reduction in striatal volume detected at 6 months. Conclusions: The PRE-CELL study has enrolled a cohort of subjects with early-stage HD and has characterized the rate of change in clinical, imaging and novel serum and CSF biomarker measures. This data will be used as a baseline for subjects who are candidates for the future planned Phase 1 trial once regulatory approval has been obtained.

Disclosure: Dr. Wheelock has nothing to disclose. Dr. Tempkin has received personal compensation for activities with Lundbeck Pharmaceuticals. Dr. Duffy has nothing to disclose. Dr. Martin has nothing to disclose. Dr. Mooney has nothing to disclose. Dr. Dayananthan has nothing to disclose. Dr. Scher has received personal compensation for activities with Lundbeck, Inc. as honorarium. Dr. Farias has nothing to disclose. Dr. Swadell has nothing to disclose. Dr. DeCarli has nothing to disclose. Dr. Brunberg has nothing to disclose. Dr. Li has nothing to disclose. Dr. Liu has nothing to disclose. Dr. Yarborough has nothing to disclose. Dr. Stout has nothing to disclose. Dr. Moscovitch-Lopatin has nothing to disclose. Dr. Hersch has nothing to disclose. Dr. Fink has nothing to disclose. Dr. Annett has nothing to disclose. Dr. Nolta has nothing to disclose.