Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN.
Open-Label Fosmetpantotenate, a Phosphopantothenate Replacement Therapy in a Single Patient with Atypical PKAN.
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DOI：
10.1155/2017/3247034
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发表时间：
2017
影响因子：
0.9
通讯作者：
Kleopa KA
中科院分区：
文献类型：
--
作者：
Christou YP;Tanteles GA;Kkolou E;Ormiston A;Konstantopoulos K;Beconi M;Marshall RD;Plotkin H;Kleopa KA
Objective.泛酸激酶相关神经变性（PKAN）是一种常染色体隐性遗传疾病，具有不同的发病、进展速度和表型表达。迟发性、进展缓慢的PKAN通常表现为神经精神和运动表现，包括言语困难、进行性肌张力障碍、强直和帕金森综合征。PKAN是由双等位基因PANK 2突变引起的，PANK 2是编码泛酸激酶2的基因，泛酸激酶2是辅酶A生物合成中的调节酶。目前的治疗策略依赖于症状缓解。我们描述了治疗的第一个，迟发性PKAN患者口服磷泛酸盐（以前称为RE-024），一种新的替代疗法，开发绕过酶缺陷。方法.这是一项开放标签、非对照、12个月的泛酸磷治疗，治疗对象为1例迟发型、中度重度和缓慢进展型PKAN患者。结果患者的所有临床参数均有所改善，包括统一帕金森病评定量表（UMRS）、Barry-Albright肌张力障碍量表、EuroQol五维三水平（EQ-5D-3L）量表、定时25英尺步行试验和电声门图语音分析。泛酸磷耐受性良好，仅出现一过性肝酶升高，在剂量降低后恢复正常，在随后的剂量增加后未复发。结论.磷泛酸盐在单个PKAN患者中显示出有希望的结果，应在对照试验中进一步研究。
Objective. Pantothenate kinase-associated neurodegeneration (PKAN) is an autosomal recessive disorder with variable onset, rate of progression, and phenotypic expression. Later-onset, more slowly progressive PKAN often presents with neuropsychiatric as well as motor manifestations that include speech difficulties, progressive dystonia, rigidity, and parkinsonism. PKAN is caused by biallelic PANK2 mutations, a gene that encodes pantothenate kinase 2, a regulatory enzyme in coenzyme A biosynthesis. Current therapeutic strategies rely on symptomatic relief. We describe the treatment of the first, later-onset PKAN patient with oral fosmetpantotenate (previously known as RE-024), a novel replacement therapy developed to bypass the enzymatic defect. Methods. This was an open-label, uncontrolled, 12-month treatment with fosmetpantotenate of a single patient with a later-onset, moderately severe, and slowly progressive form of PKAN. Results. The patient showed improvement in all clinical parameters including the Unified Parkinson's Disease Rating Scale (UPDRS), Barry-Albright Dystonia Scale, the EuroQol five-dimensional three-level (EQ-5D-3L) scale, timed 25-foot walk test, and electroglottographic speech analysis. Fosmetpantotenate was well-tolerated with only transient liver enzyme elevation which normalized after dose reduction and did not recur after subsequent dose increases. Conclusions. Fosmetpantotenate showed promising results in a single PKAN patient and should be further studied in controlled trials.