Kim Kyeongsoon, Kleinman Hynda K, Lee Hahn-Jun, Pahan Kalipada
Department of Pharmaceutical Engineering, Inje University, Gimhae, South Korea.
Polaryx Therapeutics Inc., Paramus, NJ, USA.
Orphanet J Rare Dis. 2017 Jun 17;12(1):113. doi: 10.1186/s13023-017-0663-8.
Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of genetically distinct lysosomal disorders that mainly affect the central nervous system, resulting in progressive motor and cognitive decline primarily in children. Multiple distinct genes involved in the metabolism of lipids have been identified to date with various mutations in this family of diseases. There is no cure for these diseases but some new therapeutic approaches have been tested that offer more hope than the standard palliative care. Many of the therapeutic advances require invasive procedures but some progress in slowing the disease has been found and more options can be expected in the future. We also review the literature on children with disease/conditions other than NCL for the non-invasive use, safety, and tolerability of a lipid-lowering drug, gemfibrozil, as a potential treatment for NCLs. Gemfibrozil has shown efficacy in an animal model of NCL known as CLN2 (late infantile classic juvenile) and has been shown to be safe for lowering lipids in children. Among the 200 non-NCL children found in the published literature who were treated with gemfibrozil for NCL-related problems, only 3 experienced adverse events, including 2 with muscle pain and 1 with localized linear IgA bullous dermatitis. We conclude that gemfibrozil is safe for long-term use in children, causes minimal adverse events, is well tolerated, and may delay the progression of NCLs. Gemfibrozil may potentially be an alternative to more invasive therapeutic approaches currently under investigation and has the potential to be used in combination with other therapeutic approaches.
神经元蜡样脂褐质沉积症（NCL），也被称为巴顿病，是一组基因不同的溶酶体疾病，主要影响中枢神经系统，主要导致儿童进行性运动和认知能力下降。迄今为止，已确定多个参与脂质代谢的不同基因在这一系列疾病中存在各种突变。这些疾病无法治愈，但已经测试了一些新的治疗方法，比标准的姑息治疗提供了更多希望。许多治疗进展需要侵入性操作，但已发现一些在减缓疾病方面的进展，未来有望有更多选择。我们还回顾了关于非NCL疾病/病症儿童使用降脂药物吉非贝齐作为NCL潜在治疗方法的非侵入性使用、安全性和耐受性的文献。吉非贝齐在一种名为CLN2（晚婴儿型经典青少年型）的NCL动物模型中显示出疗效，并且已证明对降低儿童血脂是安全的。在已发表文献中发现的200名因NCL相关问题接受吉非贝齐治疗的非NCL儿童中，只有3人出现不良事件，包括2人肌肉疼痛和1人局限性线状IgA大疱性皮肤病。我们得出结论，吉非贝齐对儿童长期使用是安全的，不良事件最少，耐受性良好，可能会延缓NCL的进展。吉非贝齐可能是目前正在研究的更具侵入性治疗方法的替代方案，并且有可能与其他治疗方法联合使用。
