Achievement of Therapeutic Goals Over 2 Years of Velaglucerase Alfa Enzyme Replacement Therapy in Patients with Type 1 Gaucher Disease (original) (raw)

Abstract

Background and Purpose: Late infantile neuronal ceroid lipofuscinosis (LINCL/Batten disease), is a uniformly fatal lysosomal storage disease resulting from mutations in the CLN2 gene that encodes for tripeptidyl peptidase, a lysosomal enzyme necessary for degradation of protein waste products. Onset occurs at age 2-4 years, with progressive central nervous system degeneration and death by age 8-12 years. To assess disease severity, we developed an objective measure based upon five imaging biomarkers acquired over the whole brain. Methods: Five magnetic resonance imaging (MRI) techniques were used to measure the following variables across the whole brain: 1) apparent diffusion coefficient (ADC), 2) diffusion fractional anisotropy (FA), 3) T2 relaxation times, 4) the volume percentage of cerebrospinal fluid (%CSF), and 5) N-acetylaspartate to creatine ratios (NAA/Cr). Twenty-five data sets were prospectively acquired from twenty subjects with LINCL [2.5-8.1 years, 7 male/13 female] under general anesthesia using a 3.0 Tesla MRI system. Results: We sought to determine the correlation between the combination of MRI parameters with subject age and the complement of a clinical LINCL score developed by our group. A multivariate linear regression was used to combine the five MRI biomarkers into a single score which varied with age such that R2 = 0.69,(p < 0.001) and clinical LINCL score R2 = 0.73,(p < 0.001). Conclusion: The multiparametric disease severity score obtained from the combination of ADC, FA, T2, %CSF, and NAA/Cr whole brain MRI techniques may provide a robust objective measure of disease severity in Batten disease. Further subject accrual is ongoing.

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