脊髓性肌萎缩症治疗新药――SPINRAZA

目的 :探讨新药SPINRAZA的药理作用。方法:脊髓性肌萎缩症(SMA)是一种常染色体隐性遗传性神经肌肉疾病。美国FDA已经批准SPINRAZA用于儿童和成人SMA的治疗。本文主要从作用机制、药效学、药动学、临床疗效及不良反应等方面对SPINRAZA进行综述。结果:SPINRAZA对SMA有较好的治疗作用,显著增加HFMSE评分,改善患者的运动功能。结论:SPINRAZA为一种反义寡核苷酸(SAO),能够改变SMN2基因的剪接,从而增加全功能SMN蛋白的生成,为SMA患者提供了一种重要的治疗手段。     

从利司扑兰浅谈我国罕见病药物的审评审批

利司扑兰是基于我国罕见病监管政策快速获批的脊髓性肌萎缩症(SMA)治疗药物,其注册上市有效解决了我国患者未满足的临床需求和药物可获得性问题。本文结合SMA的疾病特征和未满足临床需求,简要回顾了利司扑兰的研发过程,以及申请人在早期临床研究期间与国家药品监督管理局药品审评中心(CDE)之间的沟通交流,进而阐述了CDE对利司扑兰关键性临床研究的评估,着重介绍了有关地区间差异问题的数据分析和审评考量。这个案例不仅展现了我国监管机构从患者的临床需求出发、积极解决罕见病药物可及性的价值导向,和对罕见病人群的人文关怀,另一方面也彰显了以数据为基础、以科学为依据的审评原则。     

46例成人型脊髓性肌萎缩症临床及病理分析

目的 总结成人型脊髓性肌萎缩症（SMA4）的临床与病理学特征。方法 收集46例经肌肉活检证实的SMA4病例进行临床和病理学分析。结果 SMA4平均发病年龄38.7岁，起病与进展隐袭，预后相对良好；肌无力及肌萎缩以四肢近端为主；约四分之一患者血清CPK轻度升高；EMG示神经源性损害；肌活检主要为小群性肌萎缩，ATP酶染色见同型肌群化及肌纤维代偿性肥大。结论 根据临床表现，结合肌肉活检，可为确诊SMA4提供可靠依据。     

作用于SMN2的脊髓性肌萎缩治疗药物研究进展

脊髓性肌萎缩(spinal muscular atrophy, SMA)是一种严重的遗传性神经肌肉疾病,由于其存活运动神经元1 (survival motor neuron, SMN1)基因缺失或突变导致其编码的SMN蛋白水平降低,引起α神经元的缺失和进行性肌肉萎缩,导致运动功能的丧失和寿命的缩短。研究发现,促进SMN2基因中外显子7的包含,可产生具有完全功能的SMN蛋白,改善疾病的症状。迄今为止,包含基因治疗药物onasemnogene abeparvovec在内,只有3种用于SMA的治疗药物上市。本文简要介绍了反义寡核苷酸药物诺西那生钠(nusinersen)和小分子化学药物利司扑兰(risdiplam),并综述了处于临床及临床前研究阶段的以SMN2为靶点的小分子化学药物和反义寡核苷酸药物的研究进展。     

诺西那生钠在脊髓性肌萎缩症治疗中的生化研究

目的：探讨诺西那生钠在脊髓性肌萎缩症(SMA)治疗中对生化指标的影响。方法：选择2021年6月—2023年6月收治的SMA患儿40例,所有SMA患儿均接受诺西那生钠治疗。对比患儿治疗前后肝功能[丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、谷氨酰转肽酶(GGT)]、肾功能[尿素(BUN)、肌酐(CREA)、胱抑素C(CysC)]、肌酸激酶(CK)、脑脊液[葡萄糖(GLU)、乳酸脱氢酶(LDH)、脑脊液蛋白(TPC)]等指标的变化情况。结果：与治疗前相比,患儿治疗14 d肝功能指标(ALT,AST和GGT)均明显升高,但在治疗28 d时出现下降趋势,治疗63 d肝功能指标水平接近基线水平,差异有统计学意义(P<0.05)。患儿治疗期间肾功能指标(BUN,CREA和CysC)未出现明显变化,各项指标不同时间点对比,差异无统计学意义(P>0.05)。患儿治疗期间脑脊液指标(GLU,LDH和TPC)未出现明显变化,各项指标不同时间点对比,差异无统计学意义(P>0.05)。与治疗前相比,患儿治疗后CK明显下降,差异有统计学意义(P<0.05)。结论：SMA患...     

婴儿型脊髓性肌萎缩症1例

脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传病,累及脊髓前角运动神经元细胞,导致进行性、对称性肌萎缩和肌张力减低。本症早期发现和诊断较困难,容易误诊。笔者现就临床工作中诊治的1例脊髓性肌萎缩患儿进行分析和讨论。1病历摘要患儿男,61天,因咳嗽、气促4天,呼吸停止复苏后20分钟入院。系G1P1足月自然分娩,无产伤窒息史,人工喂养至今,既往体健。父母体健。     

诺西那生钠注射液治疗儿童脊髓性肌萎缩症疗效观察

目的:探讨脊髓性肌萎缩症(SMA)患儿应用诺西那生钠注射液的临床疗效及安全性。 方法:选取 2022 年 1-6 月于我院 接受诺西那生钠鞘内注射治疗的 SMA 患儿 26 例,于治疗当天(T0)、第 14 天(T1)、第 28 天(T2)及第 63 天(T3)评估并比较 Hammersmith 扩展功能运动量表(HFMSE)、上肢模块修订版(RULM)、6 分钟步行试验(6MWT)及不良反应发生情况。 结果:与 T0 比较,T3 时 HFMSE 评分升高[(20. 69± 14. 64 ) 分 vs. ( 23. 38± 15. 69) 分, P< 0. 01]。 与 T0 比较,T3 时 RULM 评分升高 [(18. 27±10. 15)分 vs. (19. 88±10. 21)分,P<0. 05]。 结论:SMA 患儿应用诺西那生钠注射液治疗后,HFMSE 和 RULM 评分显 著提高,近端肢体运动功能明显改善,且无明显不良反应发生     

幼儿脊髓性肌萎缩的临床特征及电生理分析

目的 分析幼儿脊髓性肌萎缩症的临床及电生理特点,探讨电生理检查对本病的诊断意义.方法 回顾性分析11例幼儿脊髓性肌萎缩症患儿的临床资料,患儿血清肌酸磷酸激酶水平,正中神经、尺神经、胫神经和腓神经运动传导检查,包括远端潜伏期、运动传导速度和复合肌肉动作电位波幅.结果 幼儿脊髓性肌萎缩症的主要临床特征为出生后不久出现进行性加重的四肢弛缓性瘫痪.所有患儿的复合肌肉动作电位波幅显著下降,伴有远端潜伏期延长和运动传导速度减缓.肌电图显示神经源性损伤.结论 婴儿型脊髓性肌萎缩症有较典型的临床及电理特征,电生理检查为本病的诊断提供重要依据.     

DHPLC联合一代测序技术在脊髓肌萎缩症携带者筛查中的应用

目的 探讨高效液相色谱联合一代测序技术进行运动神经元生存基因(survival motor neuron,SMN)缺失/点突变检测在脊髓肌萎缩症(spinal muscular atrophy,SMA)携带者筛查中的临床应用价值.方法 收集2018年1月至2019年1月就诊的3544例样本进行高效液相色谱技术(DHPL...     

Riluzole pharmacokinetics in young patients with spinal muscular atrophy

AIMS

The objective of the present study was to assess the pharmacokinetics of riluzole in patients with spinal muscular atrophy (SMA).

METHODS

Fourteen patients were enrolled in an open-label, nonrandomized and repeat-dose pharmacokinetic study. All participants were assigned to receive 50 mg riluzole orally for 5 days. Riluzole plasma concentrations were determined from samples obtained at day 5.

RESULTS

The pharmacokinetic analysis demonstrated that a dose of 50 mg once a day was sufficient to obtain a daily total exposure [AUC(0,24 h) = 2257 ng ml⁻¹ h] which was comparable with results obtained in adult healthy volunteers or ALS patients in whom a dose of 50 mg twice a day is recommended. The pharmacokinetic simulation demonstrated that the administration of 50 mg twice a day could result in higher concentrations, hence reduced safety margin.

CONCLUSION

The dose of 50 mg once a day was chosen for the clinical trial evaluating the efficacy of riluzole in SMA patients.     

New treatments in spinal muscular atrophy: an overview of currently available data

ABSTRACT

Introduction: Spinal muscular atrophy (SMA) is one of the most common inherited neuromuscular disorders. It causes progressive muscle weakness and results in significant disability. Until recently, there were no drugs available for the treatment of SMA. Several phase 1–3 studies, including three double-blind randomized placebo-controlled studies have demonstrated the efficacy of disease-modifying approaches including gene replacement therapy, antisense oligonucleotides, and splicing modifiers.

Areas covered: This article covers the publically available data on therapeutic strategies that address the underlying cause of SMA and clinical data available on approved treatments and drugs in the pipeline.

Expert opinion: The newer therapeutic options in SMA have a good safety profile and deliver a therapeutic benefit in most patients. It is essential that the recommended standards of care are delivered along with the drugs for the best outcomes. No biomarkers to distinguish responders from non-responders are available; it is important that biomarkers be identified. Early treatment is essential for the maximum efficacy of the newly available treatments.     

Investigational therapies for the treatment of spinal muscular atrophy

Introduction: Currently, there is no cure available for the hereditary neurodegenerative disease proximal spinal muscular atrophy (SMA), which is the number one genetic killer in early childhood. However, growing knowledge of SMA pathophysiology has opened new avenues for potential therapeutic interventions.

Areas covered: This review summarizes a variety of investigational therapeutic approaches for SMA. Focusing on the current state-of-the-art applications, the authors discuss the outcome of the first clinical interventions and compare the first results from the newest strategies. The achievements of the investigational drugs highlighted in this article were deduced from original articles, pharmaceutical company press releases and clinical trial results.

Expert opinion: Nearly two decades after the discovery of the disease causing gene survival motor neuron 1, many therapeutic options for SMA have been developed, some of which made it to clinical trials but could not prove their promising experimental results. Recently, big research efforts from academia, government and the pharmaceutical industry have led to the development of highly promising compounds that are currently in clinical trials, and which could lead to feasible treatment options in the future.     

左旋氨氯地平的临床药理及临床应用

本文综述了左旋氨氯地平的临床药理、近年来临床应用、不良反应及与其他药物联合应用的情况。     

Clinical pharmacology and the provision of drug information

Summary Clinical pharmacologists have a service role in the provision of drug information to individuals both in hospitals and primary health care. We present here a systematic approach in answering questions in a drug information centre (DIC), and describe the working method and the documentation of the work in a question answer (Q/A) data base.Drugline is a full-text data base offering problem-oriented drug evaluation comparable to a clinical consultation. The drug information is produced in a non-commercial drug information centre sponsored by the national health care sector and the National Corporation of Swedish Pharmacies, and run jointly by clinical pharmacologists and pharmacists.A minor part of Drugline is available in English for online searching, in parallel with Medline at the database host, the Medical Information Centre at the Karolinska Institute Library and Information Centre, and the users represent mainly medical libraries, hospital pharmacies, university clinics, and the pharmaceutical industry. A network of DICs has been organized in Swedish university hospitals with access to Drugline for searching and the storage of questions and answers.This network has the potential for expansion throughout Europe. It offers the unique possibility of complementing drug product information with problem-oriented drug information emerging from cases in the real world of prescribing.     

心血管疾病新药阿齐沙坦酯的药理与临床评价

阿齐沙坦酯(azilsartan medoxomil)是一种血管紧张素II受体拮抗剂,用于治疗高血压,可与其他抗高血压药物联用。本文参照美国FDA有关该药的申报资料,对其药理作用、药代动力学、临床评价、安全性评价及药物相互作用等进行综述。     

Clinical pharmacology — Training and career

Summary As young physicians, attending and participating in various postgraduate clinical pharmacology training programmes, it is our experience that many of our clinical colleagues are not informed about (i) the definition or functions of a clinical pharmacologist, (ii) postgraduate education opportunities, or (iii) career prospects in this field. By reviewing the training and career opportunities in a country in which the speciality is well-developed (Great Britain) it may be possible partly to answer these points.