更新于：2024-05-01

Friedreich Ataxia

Friedreich共济失调

更新于：2024-05-01

基本信息

别名

ATAXIA, FRIEDREICH、Ataxia, Friedreich、Ataxia, Friedreich Familial

+ [101]

简介

An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)

关联

项与 Friedreich共济失调相关的药物

Omaveloxolone

靶点

Nrf2

作用机制

Nrf2刺激剂

在研机构

Reata Pharmaceuticals, Inc. [+1]

原研机构

Reata Pharmaceuticals, Inc.

在研适应症

Friedreich共济失调

非在研适应症

晚期恶性实体瘤 [+4]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2023-02-28

EGb-761

靶点

NOS2

作用机制

NOS2抑制剂 [+1]

在研机构

Ipsen SA

原研机构

Dr. Willmar Schwabe GmbH & Co. KG

在研适应症

神经系统疾病 [+1]

非在研适应症

认知障碍 [+6]

最高研发阶段批准上市

首次获批国家/地区

法国

首次获批日期2002-02-28

Deferiprone

去铁酮

靶点-

作用机制

铁调节

在研机构

CHIESI Farmaceutici SpA [+3]

原研机构

Apotex, Inc.

在研适应症

镰状细胞血症 [+2]

非在研适应症

急性肾损伤 [+8]

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期1999-08-25

172

项与 Friedreich共济失调相关的临床试验

NCT06375551 / Not yet recruitingN/A

Refining and Pilot Testing a Decision Support Intervention to Facilitate Adoption of Evidence-Based Programs to Improve Parent and Child Mental Health

This proposal responds to NIMH Objective 4.2.c to develop "decision-support tools and technologies that increase the effectiveness and continuous improvement of mental health interventions" by leveraging the Family First Prevention Services Act (FFPSA) policy opportunity. First, a web-based platform to host (a) a decision-support tool and (b) automated facilitation for group decisions with the tool will be developed with state partners' feedback. Next, decision makers leading their states' FFPSA quality improvement efforts will be engaged to pilot a decision-support intervention comprised of the tool and live or automated facilitation, and to evaluate the implementation quality of evidence-based programs adopted with the decision-support intervention.

开始日期2024-07-31

申办/合作机构

Chestnut Health Systems, Inc.

[+1]

NCT06197035 / RecruitingN/AIIT

Coping and Caring for Families With Babies With Down Syndrome. A Family-centered Intervention

The objective is to compare the impact of standard infant physical therapy and the family-centered program, Coping with and Caring for Infants with Special Needs (COPCA), on infants born with Down syndrome. This is a randomized controlled trial that will be carried out in the patients' homes and outpatient settings in Spain between January 2024 and March 2024. An evaluation battery will be used that includes child and family outcomes and video analysis of therapy sessions.
The Infant Motor profile will be the primary outcome instrument.

开始日期2024-03-10

申办/合作机构

University of Seville

DRKS00032840 / RecruitingN/A

Multiorgan complexity in Friedreich Ataxia - FACROSS

开始日期2024-01-12

申办/合作机构

Uniklinik RWTH Aachen

100 项与 Friedreich共济失调相关的临床结果

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100 项与 Friedreich共济失调相关的转化医学

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0 项与 Friedreich共济失调相关的专利（医药）

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3,418

项与 Friedreich共济失调相关的文献（医药）

2024-03-14·Molecular therapy. Methods & clinical development

AAV8 gene therapy reverses cardiac pathology and prevents early mortality in a mouse model of Friedreich's ataxia.

Article

作者: Joshua C Chang ; Molly R Ryan ; Marie C Stark ; Su Liu ; Pravinkumar Purushothaman ; Fria Bolan ; Caitlin A Johnson ; Mark Champe ; Hui Meng ; Michael W Lawlor ; Sarah Halawani ; Lucie V Ngaba ; David R Lynch ; Crystal Davis ; Elena Gonzalo-Gil ; Cathleen Lutz ; Fabrizia Urbinati ; Bala Medicherla ; Carlos Fonck

Friedreich's ataxia (FRDA) is an autosomal-recessive disorder primarily attributed to biallelic GAA repeat expansions that reduce expression of the mitochondrial protein frataxin (FXN). FRDA is characterized by progressive neurodegeneration, with many patients developing cardiomyopathy that progresses to heart failure and death. The potential to reverse or prevent progression of the cardiac phenotype of FRDA was investigated in a mouse model of FRDA, using an adeno-associated viral vector (AAV8) containing the coding sequence of the FXN gene. The Fxn^flox/null::MCK-Cre conditional knockout mouse (FXN-MCK) has an FXN gene ablation that prevents FXN expression in cardiac and skeletal muscle, leading to cardiac insufficiency, weight loss, and morbidity. FXN-MCK mice received a single intravenous injection of an AAV8 vector containing human (hFXN) or mouse (mFXN) FXN genes under the control of a phosphoglycerate kinase promoter. Compared to vehicle-treated FXN-MCK control mice, AAV-treated FXN-MCK mice displayed increases in body weight, reversal of cardiac deficits, and increases in survival without apparent toxicity in the heart or liver for up to 12 weeks postdose. FXN protein expression in heart tissue was detected in a dose-dependent manner, exhibiting wide distribution throughout the heart similar to wild type, but more speckled. These results support an AAV8-based approach to treat FRDA-associated cardiomyopathy.

2024-03-14·Molecular therapy. Methods & clinical development

Perspectives of the Friedreich ataxia community on gene therapy clinical trials

Article

作者: Trantham, Shandra J. ; Coker, Mackenzi A. ; Norman, Samantha ; Crowley, Emma ; Berthy, Julie ; Byrne, Barry J. ; Subramony, Sub ; Lou, XiangYang ; Corti, Manuela

Gene therapy is a potential treatment for Friedreich ataxia, with multiple programs on the horizon. The purpose of this study was to collect opinions about gene therapy from individuals 14 years or older with Friedreich ataxia or parents/caregivers of Friedreich ataxia patients who were diagnosed as children 17 or younger. Participants were asked to complete a survey after reading brief educational materials regarding gene therapy. Most of the patients captured in this survey have an early-onset (classical) presentation of the disease. Participants expressed urgency in participating in gene therapy clinical trials despite the associated risks. About half of the respondents believed that gene therapy would cease progression or minimize symptoms, whereas nearly one-fourth expected to be cured. The survey also revealed how participants perceive their symptom burden, because a substantial majority reported that balance/walking issues most interfere with their quality of life and would be the symptom they would prioritize treating. Although not statistically significant, more caregivers prioritized treating cardiomyopathy than patients. This study provides valuable information on priorities, beliefs, and expectations regarding gene therapy and serves to guide future gene therapy opinion studies and gene therapy trial design.

2024-02-23·Annals of clinical and translational neurology

Phenotypic variation of FXN compound heterozygotes in a Friedreich ataxia cohort.

Article

作者: Megan M Shen ; Christian Rummey ; David R Lynch

OBJECTIVE:

Most individuals with Friedreich ataxia (FRDA) have homozygous GAA triplet repeat expansions in the FXN gene, correlating with a typical phenotype of ataxia and cardiomyopathy. A minority are compound heterozygotes carrying a GAA expansion on one allele and a mutation on the other. The study aim was to examine phenotypic variation among compound heterozygotes.

METHODS:

Data on FXN mutations were obtained from the Friedreich Ataxia Clinical Outcome Measures Study (FA-COMS). We compared clinical features in a single-site FA-COMS cohort of 51 compound heterozygous and 358 homozygous patients, including quantitative measures of cardiac, neurologic, and visual disease progression.

RESULTS:

Non-GAA repeat mutations were associated with reduced cardiac disease, and patients with minimal/no function mutations otherwise had a typical FRDA phenotype but with significantly more severe progression. The partial function mutation group was characterized by relative sparing of bulbar and upper limb function, as well as particularly low cardiac involvement. Other clinical features in this group, including optic atrophy and diabetes mellitus, varied widely depending on the specific type of partial function mutation.

INTERPRETATION:

These data support that the typical FRDA phenotype is driven by frataxin deficiency, especially severe in compound heterozygotes with minimal/no function mutations, whereas the heterogeneous presentations of those with partial function mutations may indicate other contributing factors to FRDA pathogenesis.

405

项与 Friedreich共济失调相关的新闻（医药）

2024-04-04

·生物探索

Cell Metab | 华中科技大学李锋/宋科翰开发一种可抑制破骨细胞骨吸收的新型Nrf2激动剂

引言通过小分子激活Nrf2是治疗绝经后骨质疏松症的一种很有前途的策略。然而，目前还没有批准用于治疗慢性疾病的Nrf2激活剂，Nrf2调控破骨细胞分化的下游机制尚不清楚。2024年4月2日，华中科技大学李锋及宋科翰共同通讯在Cell Metabolism 在线发表题为“A clinical-stage Nrf2 activator suppresses osteoclast differentiation via the iron-ornithine axis”的研究论文，该研究表明bitopertin，一种临床阶段的甘氨酸摄取抑制剂，通过激活Nrf2抑制破骨细胞分化并改善卵巢切除术诱导的骨质流失。从机制上讲，bitopertin与Keap1 Kelch结构域相互作用，减少Keap1-Nrf2结合，导致Nrf2泛素化和降解减少。在小鼠和人类受试者中，与临床批准的Nrf2激活剂相比，Bitopertin与更少的不良事件相关。此外，Nrf2转录激活铁转运蛋白编码基因Slc40a1，以降低破骨细胞内的铁水平。Nrf2缺失或补铁上调鸟氨酸代谢酶Odc1，从而降低鸟氨酸水平，从而促进破骨细胞分化。总之，该研究确定了一种新的临床阶段Nrf2激活剂，并提出了破骨细胞中一种新的Nrf2-铁-鸟氨酸代谢轴。绝经后骨质疏松症是在缺乏雌激素的情况下由破骨细胞过度活化引起的代谢紊乱。骨密度(BMD)的降低使患者髋部或椎体脆性骨折的风险增加，在全球范围内造成严重的残疾和社会经济负担破骨细胞在巨噬细胞集落刺激因子(M-CSF)和核因子kB配体受体激活剂(RANKL)的刺激下向骨髓源性巨噬细胞(bmdm)分化。用双膦酸盐化合物靶向破骨细胞是治疗骨质疏松症的主流策略。然而，严重的不良反应和较差的依从性是许多患者标准化双膦酸盐治疗的障碍，导致骨质疏松症治疗不足需要发现新的治疗靶点，以确保对这些患者提供更好的护理。核因子E2相关因子2 (Nrf2)是一种氧化还原相关的转录因子，其激活可通过抑制破骨细胞分化来改善绝经后骨质疏松症。在非胁迫条件下，Nrf2被Keap1隔离在细胞质中，并被Cul3泛素连接酶泛素化，用于蛋白酶体降解在氧化应激过程中，Nrf2与Keap1分离并易位到细胞核，激活多种参与细胞抗氧化反应的细胞保护基因。这些基因的Nrf2结合位点被称为抗氧化反应元件(AREs)由于具有细胞保护作用，已经发现了许多Nrf2激活因子。然而，它们中的大多数是亲电性和间接Nrf2激活剂，共价靶向KEAP1中的半胱氨酸151，其中只有两种被批准用于临床使用，即延胡索酸二甲酯(DMF)用于治疗复发型多发性硬化症和omaveloxolone (OMA)用于治疗弗里德赖希共济失调。除Keap1外，这些亲电Nrf2激活因子还与其他关键酶或蛋白质的半胱氨酸残基相互作用并影响其功能，导致“脱靶”和毒性作用。在人类中，在临床试验中，间接Nrf2激活剂与高不良事件发生率相关另一种策略是找到Keap1-Nrf2相互作用的直接抑制剂来选择性激活Nrf2。然而，直接Nrf2激活剂通常分子大小较大，这降低了其进入中枢神经系统治疗相关疾病的能力，目前尚无临床批准的直接Nrf2激活剂。因此，开发更安全、更有效的Nrf2激活剂用于临床仍然是一个挑战。模式图（Credit: Cell Metabolism）Bitopertin是一种口服、临床甘氨酸转运蛋白1 (Glyt1)抑制剂，最初用于治疗精神分裂症。最近，bitopertin被FDA授予孤儿药资格，用于治疗红细胞生成性卟啉原症(EPP)，这是一种罕见的、使人衰弱的、潜在威胁生命的血液疾病。bitopertin治疗EPP的疗效正在两项正在进行的2期临床试验AURORA (NCT05308472)和BEACON (ACTRN12622000799752)中进行评估bitopertin的潜在临床应用是基于其限制甘氨酸摄取的作用。有趣的是，骨质疏松症患者的血清甘氨酸水平明显高于骨密度正常的患者。另一项研究显示，甘氨酸支持谷胱甘肽的形成，并有助于脂多糖刺激后BMDMs中白细胞介素(IL)-1β的产生，表明甘氨酸具有促炎作用。然而，目前尚不清楚甘氨酸水平升高是否与骨质疏松症有因果关系，以及甘氨酸是否影响BMDMs向破骨细胞的分化。该研究发现bitopertin，而不是甘氨酸补充剂，通过Nrf2激活改善卵巢切除术(OVX)诱导的骨质疏松症。在机制上，bitopertin与Kelch结构域相互作用，减少Keap1-Nrf2相互作用，减少Nrf2降解。与现有的临床Nrf2激活剂相比，Bitoeprtin在人类受试者中更安全，与更少的不良事件相关。更重要的是，该研究发现了一个新的Nrf2 -铁-鸟氨酸代谢轴在破骨细胞分化。该研究结果表明，bitopertin在治疗骨质疏松症中具有先前未被认识到的治疗作用，并有助于阐明Nrf2对破骨细胞作用的分子机制。原文链接https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00084-6责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述

临床结果临床1期临床2期

2024-04-02

·药明康德

阿尔茨海默病、帕金森病……研发格局一览

▎药明康德内容团队编辑随着Leqembi获批为阿尔茨海默病（AD）治疗领域带来的显著进展，神经病学（Neurology）领域近年来受到业界的高度关注。这一趋势不仅促进了大型交易的频繁发生，也推动了临床研究积极进展。近日，行业媒体Evaluate发布了一份行业报告，深入分析了神经病学领域内的交易动态和研发趋势。在今天的文章里，药明康德内容团队将结合公开资料，与读者分享其中的精彩内容。点击文末“阅读全文/Read more”，即可访问报告原文网址。近年神经病学领域的大型收购与交易趋势神经病学是一门专注于神经系统疾病的医学分支，涵盖了从退行性疾病（如阿尔茨海默病和帕金森病）到癫痫、抑郁症、偏头痛、疼痛管理，乃至众多罕见疾病的广泛领域。相较于如癌症这样的高关注度领域，神经病学在过去数十年里获得的投资相对缺乏，这导致了大量未竟医疗需求。这种投资不足的背景，结合持续的精神健康危机和有限的治疗选择，为神经病学领域带来了独特的市场机遇和挑战。图片来源：123RF2022-2023年间，神经病学领域的并购活动活跃，其中较为突出的例子包括百时美施贵宝（Bristol Myers Squibb）以约140亿美元收购Karuna Therapeutics，此举旨在将精神分裂症疗法KarXT（xanomeline-trospium）纳入其产品管线，该药物的新药申请（NDA）已被美国FDA受理，有望在今年获得批准。艾伯维（AbbVie）则在去年12月以约87亿美元收购Cerevel Therapeutics，进一步加强艾伯维在神经病学领域的布局。此外，渤健（Biogen）以约73亿美元收购Reata Pharmaceuticals，获得了其针对弗里德赖希共济失调症的药物Skyclarys（omaveloxolone）。辉瑞（Pfizer）公司也加大了在神经病学领域的投入，于2022年以总计约116亿美元收购Biohaven Pharmaceutical，增强了其偏头痛治疗产品组合。这一系列并购案例不仅展示了大型医药企业在神经病学领域的布局，也凸显了该领域积极的发展前景。尽管过去神经病学曾经面临投资不足的挑战，但如今它正吸引着大型药企的集中关注和大规模投资。▲2014-2024年间，神经病学领域內＞10亿美元的交易活动（药明康德内容团队制表，数据来源：参考资料[1]）回顾近年来神经病学领域的交易活动，显而易见的一种趋势是医药公司对于“低风险、后期研发阶段项目”的偏好。神经病学药物开发的历程充满了挑战，多个项目在研发过程中曾遭遇了不可预见的挫折，凸显了该领域内药物开发的固有不确定性和高风险。鉴于此，相较于那些仍处于探索初期、前景充满不确定性的新药项目，大部分医药公司更倾向于投资于那些已经进入到后期研发阶段、相对风险更低的项目。这种策略反映了企业对于风险管理的审慎态度，以及在资本投入时寻求更高确定性的倾向，有些公司甚至避免涉足处于中期临床研究阶段项目的风险，倾向于在药物研发进展到更加成熟和风险更可控的阶段进行投资或并购。除了频繁的并购活动外，近年来神经病学领域的融资活动也十分活跃。在2024年3月，Engrail Therapeutics完成了1.57亿美元的B轮融资。而就在不久前，Alto Neuroscience也成功完成了初次IPO交易。2023年9月，Neumora Therapeutics也实现了上市，募集资金高达2.5亿美元。Neumora的主要产品navacaprant目前正处于针对抑郁症的3期临床试验阶段，该公司预计这一关键试验结果将为预定于2025年递交的新药申请提供支持。这些融资活动凸显了产业在神经病学领域的高度活跃性，也展示该领域在医药研发和创新方面的巨大潜力。图片来源：123RF神经病学领域的新药研发趋势随着科技的不断进步以及我们对人脑复杂机制的深入理解，神经病学领域正处于一场创新疗法和药物开发的浪潮中。在此过程中，一些关键趋势尤为突出：首先，药物的选择性变得更加精准，能够特异性地调节特定的神经通路或受体，旨在降低副作用并提升治疗效果。其次，致幻药物在精神疾病治疗中的潜在应用正受到重新评估，特别是在治疗抑郁症和创伤后应激障碍（PTSD）方面。此外，人工智能（AI）技术正助力脑部药物的发现和开发，加速了新药候选分子的筛选和优化过程。同时，对新分子和创新作用机制的探索正不断扩大治疗工具箱，为患者提供更多的治疗选择。这些进展共同推动了神经病学领域的创新和发展，为未来治疗带来新的希望。1.新一代药物更具选择性在开发更有效和安全的中枢神经系统药物方面，药物选择性的提高是一个重要因素。以强生公司（Johnson & Johnson）的aticaprant和Neumora公司的navacaprant为例，这两种药物针对Kappa阿片受体（KORs）的选择性上优于对μ或δ等其他阿片受体亚型，展现了对KORs的高度特异性。这种特性使得这两种药物在治疗重度抑郁症的3期临床试验中表现出潜力，并且还有望扩展到治疗焦虑症和药物滥用等领域。这种对特定受体的高选择性不仅提高了治疗的针对性，也有望减少潜在的副作用。2.重新思考致幻药物的药用价值近来，迷幻药物的医疗用途得到了重新评估和认可。今年2月，美国FDA宣布受理Lykos Therapeutics（前MAPS公益公司）为3，4-亚甲二氧基甲基苯丙胺（MDMA）递交的新药申请，用于治疗PTSD。该申请还获得了FDA授予的优先审评资格，预计审评结果将于今年8月11日之前发布。新闻稿指出，若该药物获批，它将成为第一款MDMA辅助疗法，同时也是首个获批的迷幻药辅助疗法。此外，Compass Pathways公司的在研裸盖菇素（psilocybin，致幻蘑菇中的致幻成分）疗法在2期临床试验中取得了积极结果，目前已进入治疗耐药性抑郁症的3期临床试验。大麻也正式进入医疗领域。例如，Jazz Pharmaceuticals的癫痫发作药物Epidiolex（cannabidiol，大麻的一个主要非致幻成分）在2018年获得FDA的批准上市，治疗两类罕见而严重的癫痫。新闻稿指出，这是首款获美国FDA批准上市的含纯化大麻提取物的新药。人们对致幻剂疗法潜力的兴趣与日俱增，促使FDA在2023年年中起草了指南草案，以支持相关临床研究，这标志着迷幻药物作为治疗手段就正在逐步正规化和科学化。3.AI辅助神经药物开发2024年，Alto Neuroscience成功地募集到1.29亿美元上市。Alto公司以“人工智能驱动的大脑精准医疗”为其核心理念，专注于AI辅助精准药物开发。其成功的融资活动背后是基于该公司主打项目展示出的积极研究数据：公司的ALTO-300项目相关研究显示，采用脑电图（EEG）生物标志物辅助筛选的患者相较于未使用EEG筛选患者获得了更大的益处。在神经病学领域，精准医疗仍处于起步阶段。然而，新兴的测序技术、传感器工具以及更为强大的数据分析能力正助力科学家们深入解析大脑的复杂机制。值得关注的是，2024年初，美国FDA批准了一项名为BrainSee的人工智能临床测试，专门用于阿尔茨海默病。该测试结合大脑成像技术和认知评估，旨在预测患者从轻度认知障碍进展到痴呆症的可能性，标志着人工智能在神经病学领域应用的一大进步。图片来源：123RF4.新靶点，新机制随着基因研究在神经病学领域的深入，新的治疗靶点不断涌现。例如，Denali Therapeutics和渤健合作开发的LRRK2靶向抑制剂BIIB122/DNL151，目前处于治疗帕金森病的2b期试验阶段。另外，Alector Therapeutics正在与艾伯维合作进行一项2b期临床研究，评估其TREM2靶向疗法AL002用以治疗阿尔茨海默病的作用。此外，Alector还与GSK达成合作，共同开发两款progranulin靶向单抗AL001和AL101以治疗神经退行性疾病。Lexeo Therapeutics正在研发的基因疗法LX1001，旨在通过递送APOE2基因—一种具有保护作用的基因——来降低携带纯合APOE4基因患者罹患阿尔茨海默病的风险。该候选药物目前正在进行1/2期临床试验，初步研究数据表明，接受低剂量LX1001治疗的患者脑脊液中的APOE2蛋白表达增加，在超过12个月的随访期内，两名患者的脑脊液中tau蛋白和磷酸化tau蛋白水平与基线相比降低，这两种蛋白是反映阿尔茨海默病患者大脑关键病理变化的生物标志物。图片来源：123RF神经病学领域的弄潮儿在神经病学领域的创新浪潮中，众多公司凭借其独特的技术优势和丰富的产品线，促进了该领域的快速发展，并为治疗神经病学相关疾病提供了更广泛的选择。接下来，我们将介绍几家近年来专注于神经病学领域的公司。Neurocrine BiosciencesNeurocrine Biosciences专注于为患有神经性、神经内分泌性及神经精神疾病的患者开发新型治疗方案。该公司的产品组合多样化，包括已经获得FDA批准的Ingrezza，这是一款已获批用于治疗迟发性运动障碍和亨廷顿病相关舞蹈症的药物。除此之外，Neurocrine还拥有一系列正处于中到后期临床开发阶段的候选疗法。▲Neurocrine Biosciences在研管线（图片来源：Neurocrine Biosciences官网）Acadia PharmaceuticalsAcadia公司已有2款药物获得FDA批准，分别是Nuplazid（pimavanserin）和Daybue（trofinetide）。根据Acadia公司官网，pimavanserin是美国FDA批准的首个用于治疗帕金森病精神病相关幻觉和妄想症状的处方药。值得一提的是，该药物针对精神分裂症的阴性症状的适应症目前正处于3期临床研究中，此前公布的2期试验结果表明，当与现有抗精神病药物联合用药治疗精神分裂症患者时，该药物显著改善了患者在NSA-16量表上的表现。Acadia预计在2024年获得pimavanserin的3期研究的顶线结果。Daybue则是Acadia公司的第二款获批产品，它在2023年3月获得FDA批准用于治疗Rett综合征成人和2岁以上儿童患者，成为FDA批准的首款治疗Rett综合征的药物。▲Acadia Pharmaceuticals在研管线（图片来源：Acadia Pharmaceuticals官网）Alector TherapeuticsAlector公司的研发管线包含3个处在临床阶段的潜在“first-in-class”项目，这些项目吸引了包括GSK和艾伯维在内的大型医药公司的合作。其中，AL001和AL101是与GSK合作开发的两种新型单抗。AL001目前正在进行一项关键性3期临床试验，用于治疗因GRN基因突变而存在额颞叶痴呆（FTD）风险、或患有额颞叶痴呆的患者。而AL101目前则处于2期临床试验阶段，旨在治疗阿尔茨海默病。此外，Alector管线中的AL002是一种针对TREM2的在研人源化单抗，TREM2是散发性AD的一个重要遗传风险因素。该产品由Alector和艾伯维合作开发，目前正在一项2期临床试验中接受检验。▲Alector Therapeutics在研管线（图片来源：Alector Therapeutics官网）渤健渤健在神经病学领域拥有深厚的研发历史和广泛的产品组合，包括19款已经上市的产品，涵盖了多个重要的治疗领域。其中包括首款获得FDA完全批准的阿尔茨海默病疗法Leqembi，以及基于生物标志物加速批准的首款基于生物标志物加速批准的肌萎缩侧索硬化症（ALS）疗法Qalsody（tofersen）。渤健的研发管线中也不乏创新药物，如针对tau蛋白的反义寡核苷酸（ASO）疗法BIIB080，在针对轻度阿尔茨海默病患者的1b期临床试验中展现了积极结果，使其成为首款被证明可以减少tau蛋白聚集、并展现对患者临床结局有利的趋势的tau蛋白靶向药物。此外，渤健还正在开发针对LRRK2的小分子抑制剂BIIB122，展现了其在神经病学领域研发的广度与深度。Denali TherapeuticsDenali Therapeutics致力于开发治疗神经退行性疾病和溶酶体贮积症疗法。Denali拥有多样化的产品管线，其中多个项目已经步入中后期临床开发阶段。包含与渤健合作开发用于治疗帕金森病的LRRK2小分子抑制剂DNL151，与赛诺菲（Sanofi）合作研发用于治疗多发性硬化的RIPK1小分子抑制剂SAR443820/DNL788，以及基于Denali的转运载体平台技术构建的融合蛋白药物DNL310。DNL310可被成功递送到大脑从而缓解II型黏多糖贮积症（MPS II）的中枢神经系统症状。目前，DNL310正在2/3期临床试验中接受评估，Denali公司的目标是在今年完成2/3期临床试验的患者注册。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料：[1] EVALUATING: Neurology，Retrieved April 2, 2024 from https://www.evaluate.com/thought-leadership/evaluating-neurology/?utm_source=Eloqua&utm_medium=Email&utm_campaign=202403-CMP-TL-NEUROLOGY&utm_content=EVALPHARMA-EMN-TL-2403GL-NEUROLOGY-DLRT免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

并购申请上市

2024-03-25

·BioSpace

Health Canada grants approval of the Eye-Tracking Neurological Assessment for Multiple Sclerosis (ETNA-MS) for use in tracking disease progression in people living with MS

More than 90,000 Canadians—or one in 400 people across Canada—live with multiple sclerosis (MS),1 a neurodegenerative, chronic condition that affects the central nervous system.2 Despite decades of progress on the therapeutics front, the way disease progression is detected remains vastly unchanged. Approval of ETNA™-MS has the potential to advance a new generation of care in MS, empower clinicians with a tool to identify disease progression earlier and facilitate more efficient healthcare access and delivery for people living with MS. MONTRÉAL, March 25, 2024 /CNW/ - Health Canada has granted approval of the Eye-Tracking Neurological Assessment for Multiple Sclerosis (ETNA™-MS). Developed by Innodem Neurosciences (Innodem), ETNA™-MS is a software as a medical device (SaMD, class II) intended to administer a non-invasive test and provide an Expanded Disability Status Scale (EDSS) score in the range between 1.0 and 4.5 for use in tracking disease progression in people living with MS. ETNA™-MS turns an iPad Pro into a medical device capable of capturing and analyzing several hundreds of eye movement parameters. This patented, mobile, software technology could offer a modernized approach to care and a way to make informed, real-time treatment decisions for people living with MS. The approval of ETNA™-MS is based on data collected through a validation study performed by Innodem. An ongoing longitudinal observational trial supported by Novartis Pharmaceuticals Canada Inc. (Novartis Canada) aims to investigate the potential utility of biomarkers in monitoring MS disease status. The work between Novartis Canada and Innodem seeks to accelerate the path towards a reliable, non-invasive, sensitive, and accessible marker of disease progression in MS. "This approval brings us one step further in closing the gap in care for people living with MS and marks a shift to a more proactive approach to disease management," said Erin Keith, Vice President, Neuroscience at Novartis Canada. "Through our commitment to reimagine medicine and cross-sector collaboration, we are taking innovation in MS beyond therapeutics, paving a path to much needed solutions that Canadians deserve. I am excited to see what the future holds." Canada has one of the highest rates of MS in the world,2 with more than 90,000 Canadians—or one in 400 people across Canada—living with it. MS is a complex and unpredictable disease, in which the severity and duration of symptoms can vary from person to person and evolve as the disease progresses.2 As such, people living with MS require tailored, personalized, and adaptive treatment strategies based on individual needs and the rate of disease evolution.3 "We've learned a lot about MS and its progressive nature over the years, but we still hadn't established a reliable and accessible means through which to monitor subtle changes in disease status in near real-time," said Dr. Giacomini, MS Clinic Director at the Montreal Neurological Institute and Chief Medical Officer at Innodem Neurosciences. "This approval brings us one step closer to giving clinicians a tool that could help inform better clinical decision-making and offer more positive outcomes for people living with MS." The necessity of using biomarkers in studying major diseases such as cancer and heart disease has been widely discussed,4 and today, there is an increased interest to develop disease-specific biomarkers that could estimate disease severity and cognitive status in people living with MS. In recent years, there has been a remarkable increase in the number of available treatments for MS,5 but how disease progression is detected and monitored has remained vastly unchanged. "When someone is diagnosed with MS, it changes their life," said Diego Mena Martínez, Executive Director, Quebec Division of MS Canada. "It can be a challenging condition to manage given its unpredictable nature, so I welcome the progress happening in this space as an important step towards a more proactive care approach which has the potential of positively impacting people living with this disease." As a leader in life sciences, Novartis Canada is pushing the boundaries of innovation beyond the traditional confines of therapeutics, focusing on the expansion of research to support the identification of novel biomarkers in MS. Having signed a multimillion, multi-year commercial framework agreement with Innodem to continue advancing research into the application of ETNA™-MS, with additional milestones anticipated in the future, Novartis Canada is committed to helping advance a more proactive care approach in MS. About Novartis Novartis is a focused innovative medicines company. Every day, we work to reimagine medicine to improve and extend people's lives so that patients, healthcare professionals and societies are empowered in the face of serious disease. Our medicines reach more than 250 million people worldwide. Reimagine medicine with us: Visit us at and connect with us on LinkedIn, Facebook, X/Twitter and Instagram. In Canada, Novartis Pharmaceuticals Canada Inc. employs approximately 600 people to serve the evolving needs of patients and the healthcare system and invests over $30 million in R&D yearly in the country. For more information visit . About Innodem Neurosciences Innodem Neurosciences is a leading digital biomarker and AI company specializing in the development of a proprietary, mobile, non-invasive eye-tracking technology called ETNA™ (Eye Tracking Neurological Assessment). ETNA™-MS is software as a medical device (SaMD, class II) that can be used in clinic or remotely through patient self-testing. ETNA™-MS captures patient responses to brief oculomotor tests displayed on the screen of an iPad Pro within 10 minutes. These tasks are designed to assess several key neurological functions known to be affected by multiple sclerosis, and to capture several hundred eye movement parameters in response to visually presented stimuli during specifically designed eye-tracking tests. The eye movement data is then analyzed by powerful machine learning algorithms to provide an EDSS score (between 1 and 4.5) that is correlated to the EDSS score obtained by a specialized MS clinician, potentially improving efficiencies and access to care. The ETNA™ technology is also being further validated in ongoing observational trials with participants diagnosed with other neurodegenerative and mental disorders, such as Parkinson's disease, Alzheimer's disease, Friedreich's ataxia, and cancer-related cognitive disorders ("chemo brain"). Innodem's core team, led by cognitive neurologist and CEO Dr. Étienne de Villers-Sidani, is made up of an intersectional group of neuroscientists, software engineers, data scientists, healthcare professionals and serial entrepreneurs. The company's mission is to become the leading digital biomarker and AI company to better serve the needs of the global health system. For further information, please consult . SOURCE Novartis Pharmaceuticals Canada Inc.

临床研究