University of Rochester, Rochester, NY 14642, USA.
J Inherit Metab Dis. 2011 Oct;34(5):1075-81. doi: 10.1007/s10545-011-9346-0. Epub 2011 May 10.
Juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3 disease; Batten disease) is an autosomal recessive neurodegenerative disease of childhood that typically presents at school age with vision loss followed by progressive cognitive decline, motor dysfunction, seizures, and behavior problems. No therapy has been shown to slow the progression of disease in JNCL patients, and all current treatments are symptomatic. Flupirtine has been shown in vitro to reduce apoptosis in CLN3 lymphocytes. Based on that preclinical study, several children with JNCL were given flupirtine by their parents. The purpose of this study was to determine if there was evidence of attenuated disease progression in any JNCL symptom domain. We administered a survey to parents of JNCL children to qualitatively assess flupirtine efficacy. We used the Unified Batten Disease Rating Scale (UBDRS) to determine specific aspects of disease progression and investigated three age-related factors: loss of independent ambulation, loss of intelligible speech, and loss of ability to perform independent activities of daily living. The median scores for the UBDRS physical, behavior, and capability subscales were determined in flupirtine-exposed subjects and compared to age-, sex-, and genotype-matched subjects who had never taken flupirtine. Twenty-one percent of survey responders reported administering flupirtine to their JNCL child, and 56% of these families perceived beneficial changes that they attributed to flupirtine. However, our quantitative, prospectively obtained data did not show any change in JNCL disease progression that could be attributed to flupirtine. This study highlights the need for prospective experimental therapeutic research.
青少年神经元蜡样脂褐质沉积症(JNCL;CLN3 病;Batten 病)是一种常染色体隐性遗传的儿童神经退行性疾病,通常在学龄期以视力丧失为首发症状,随后出现进行性认知下降、运动功能障碍、癫痫发作和行为问题。目前尚无治疗方法可减缓 JNCL 患者的疾病进展,所有现有治疗均为对症治疗。氟吡汀在体外已被证明可减少 CLN3 淋巴细胞的凋亡。基于该临床前研究,一些 JNCL 患儿的父母让他们服用氟吡汀。本研究旨在确定氟吡汀是否能减轻任何 JNCL 症状领域的疾病进展。我们对 JNCL 患儿的父母进行了一项调查,以定性评估氟吡汀的疗效。我们使用统一 Batten 病评定量表(UBDRS)来确定疾病进展的具体方面,并研究了三个与年龄相关的因素:丧失独立行走能力、丧失清晰言语能力和丧失独立日常生活活动能力。在接受氟吡汀治疗的受试者中确定 UBDRS 身体、行为和能力子量表的中位数评分,并将其与从未服用过氟吡汀的年龄、性别和基因型匹配的受试者进行比较。调查响应者中有 21%报告给他们的 JNCL 患儿服用了氟吡汀,其中 56%的家庭认为有有益的变化,他们将这些变化归因于氟吡汀。然而,我们的前瞻性、定量数据并未显示氟吡汀可导致 JNCL 疾病进展的任何变化。本研究强调了前瞻性实验治疗研究的必要性。