背景:亨廷顿病(HD)是一种常染色体显性神经退行性疾病,表现为进行性运动障碍以及认知和精神问题。它是由亨廷顿基因外显子1中的胞嘧啶-腺嘌呤-鸟嘌呤(CAG)扩增引起的,该基因编码突变的亨廷顿蛋白(mHTT)随着时间的推移在细胞中积累,导致功能障碍,然后通过新的毒性功能获得机制死亡。自噬已被证明对于导致神经退行性疾病的多种胞浆内聚集倾向蛋白的降解至关重要。包括mHTT。从一个富含批准药物的图书馆的屏幕上,选择非洛地平作为在HD临床前模型中表现出强自噬诱导作用的最合适的候选者。我们是,因此,进行一项试验,以评估非洛地平在早期HD患者中的安全性和耐受性。
方法:FELL-HD是第二阶段,单中心,开放标签,早期HD患者的剂量发现试验。18名具有该疾病早期临床特征的参与者将接受非洛地平治疗58周,再进行为期4周的随访。主要结果指标是可归因于非洛地平的不良事件的数量。探索性结果包括运动和认知功能的其他测量,非运动症状和生活质量量表,以及通过脑MRI评估的外周和中枢疾病生物标志物。血液和脑脊液的分析也将通过相关的样本研究进行,FELLHD-S.
背景:该研究获得了伦敦-布伦特研究伦理委员会的批准(参考22/LO/0387),并已被药品和保健产品监管机构接受临床试验授权(参考CTA12854/0256/001-0001)。试验结果的摘要将上传到我们的研究小组网站,该网站可公开访问。网络研讨会或当面开放日,向参与者和参加我们中心的更广泛的患者群体展示试验结果,审判完成后将举行。试验结果还将发表在科学杂志上,并在国家和国际会议上发表。
背景:EudraCT-2021-000897-27,ISRCTN56240656。
BACKGROUND: Huntington\'s disease (HD) is an autosomal dominant neurodegenerative disorder that presents with a progressive movement disorder along with cognitive and psychiatric problems. It is caused by a Cytosine-adenin-guanine (CAG) expansion in exon 1 of the huntingtin gene which codes for mutant huntingtin (mHTT) that over time accumulates in cells, causing dysfunction and then death through new toxic gain-of-function mechanisms. Autophagy has been shown to be critical for the degradation of diverse intracytoplasmic aggregate-prone proteins that cause neurodegenerative disease, including mHTT. From a screen of a library enriched in approved drugs,
felodipine was selected as the most suitable candidate showing strong autophagy-inducing effects in preclinical models of HD. We are, therefore, conducting a trial to assess the safety and tolerability of
felodipine in people with early HD.
METHODS: FELL-HD is a phase II, single-centre, open-label, dose-finding trial in people with early HD. 18 participants with early clinical features of the disease will be treated with
felodipine for 58 weeks, with a further 4-week follow-up. The primary outcome measure is the number of adverse events attributable to
felodipine. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life scales, as well as peripheral and central disease biomarkers assessed through brain MRI. Analysis of blood and cerebrospinal fluid will also be performed through an associated sample study, FELL HD-s.
BACKGROUND: The study was approved by the London-Brent Research Ethics Committee (reference 22/LO/0387) and has been accepted by the Medicines and Healthcare products Regulatory Agency for clinical trials authorisation (reference CTA 12854/0256/001-0001). A lay summary of the results of the trial will be uploaded to our research group website which is publicly accessible. A webinar or in-person open day, to present results of the trial to participants and our wider cohort of patients who attend our centre, will be held once the trial is completed. The results of the trial will also be published in scientific journals and presented at national and international conferences.
BACKGROUND: EudraCT-2021-000897-27, ISRCTN56240656.