Recombinant botulinum toxin with improved safety and effectiveness for treatment of dystonia

重组肉毒杆菌毒素可提高肌张力障碍治疗的安全性和有效性

基本信息

  • 批准号:
    10391609
  • 负责人:
  • 金额:
    $ 27.66万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-03-01 至 2024-02-29
  • 项目状态:
    已结题

项目摘要

Abstract Botulinum neurotoxin (BoNT) is the most toxic protein known to science. It is also the active ingredient in ® pharmaceutical products like Botox (Allergan), which have proven safe and effective for multiple neuromuscular indications. All current BoNT products are manufactured from Clostridium botulinum cultures and have similar safety characteristics, which include limitations on dosing and a black box warning in labeling. Because of its inherent toxicity and narrow therapeutic window, optimal clinical outcomes are difficult to achieve in indications involving large muscle groups, such as cervical dystonia, post-stroke spasticity and pediatric cerebral palsy. Though improved muscle tone can clearly be achieved, clinicians tend to dose on the side of caution, and overall clinical outcomes leave significant room for improvement. We here propose building on data generated with a previous candidate for a “safer BoNT” pharmaceutical (SBIR Phase 1 1R41NS086115-01A1) which found that specific amino acid substitutions to BoNT/A1 can produce a recombinant BoNT/A1 with an improved safety margin compared to wt BoNT/A1, (US 8,865,186). The initial lead candidate designed and tested, Cyto-012, had an improved safety margin, but its absolute potency was such that doses required for efficacy were also immunogenic. Here, we propose testing a new recombinant BoNT/A1 derivative termed Cyto-014, designed to have potency and immunogenicity similar to wt BoNT/A1, while retaining the desired improvement in safety suggested by our Preliminary Studies. This proposal is intended to compare the dose-response behavior, safety margin and maximum tolerated dose of Cyto-014 relative to wt BoNT/A1 in appropriately powered studies, and to evaluate its immunogenicity and effectiveness for repeat treatment. Successful completion of the proposed studies will support a Phase II study to focus on pre-clinical development activities aimed at filing an IND.
摘要 肉毒杆菌神经毒素(BoNT)是科学上已知的毒性最大的蛋白质。它也是活性成分, ® 像肉毒杆菌素(Allergan)这样的药物产品,已被证明对多种神经肌肉疾病安全有效。 迹象。所有目前的BoNT产品都是由肉毒梭菌培养物制造的,并且具有类似的 安全性特征,包括剂量限制和标签中的黑框警告。由于其 固有毒性和狭窄的治疗窗,在适应症中难以实现最佳临床结局 涉及大的肌肉群,如颈部肌张力障碍,中风后痉挛和小儿脑瘫。 虽然可以明显改善肌肉张力,但临床医生倾向于谨慎用药,总体而言, 临床结果留下显著的改进空间。我们在这里建议建立在使用 先前的候选“更安全的BoNT”药物(SBIR第1阶段1 R41 NS 086115 - 01 A1)发现, 对BoNT/A1的特定氨基酸取代可以产生具有改善的安全性的重组BoNT/A1 与wt BoNT/Al(US 8,865,186)相比的余量。最初设计和测试的主要候选人Cyto-012, 安全范围改善,但其绝对效力使得有效性所需的剂量也 免疫原性。在这里,我们建议测试一种新的重组BoNT/A1衍生物,称为Cyto-014,旨在 具有与wt BoNT/A1相似的效力和免疫原性,同时保持所需的安全性改善 根据我们的初步研究。本建议旨在比较剂量反应行为、安全性 在适当把握度的研究中,Cyto-014相对于wt BoNT/A1的边际和最大耐受剂量,以及 评价其免疫原性和重复治疗的有效性。圆满完成拟议的 研究将支持II期研究,重点关注旨在提交IND的临床前开发活动。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

PHILIP Arthur BAND其他文献

PHILIP Arthur BAND的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('PHILIP Arthur BAND', 18)}}的其他基金

Development of B8C1ad as an Orphan Drug for Iatrogenic Botulism
B8C1ad 作为治疗医源性肉毒杆菌中毒的孤儿药的开发
  • 批准号:
    10603832
  • 财政年份:
    2023
  • 资助金额:
    $ 27.66万
  • 项目类别:
Recombinant botulinum toxin with improved safety and effectiveness for treatment of dystonia
重组肉毒杆菌毒素可提高肌张力障碍治疗的安全性和有效性
  • 批准号:
    10581600
  • 财政年份:
    2022
  • 资助金额:
    $ 27.66万
  • 项目类别:
Recombinant Botulinum Neurotoxin for Treatment of Spastic Disorders
用于治疗痉挛性疾病的重组肉毒杆菌神经毒素
  • 批准号:
    8779301
  • 财政年份:
    2014
  • 资助金额:
    $ 27.66万
  • 项目类别:

相似海外基金

Planar culture of gastrointestinal stem cells for screening pharmaceuticals for adverse event risk
胃肠道干细胞平面培养用于筛选药物不良事件风险
  • 批准号:
    10707830
  • 财政年份:
    2023
  • 资助金额:
    $ 27.66万
  • 项目类别:
Hospital characteristics and Adverse event Rate Measurements (HARM) Evaluated over 21 years.
医院特征和不良事件发生率测量 (HARM) 经过 21 年的评估。
  • 批准号:
    479728
  • 财政年份:
    2023
  • 资助金额:
    $ 27.66万
  • 项目类别:
    Operating Grants
Analysis of ECOG-ACRIN adverse event data to optimize strategies for the longitudinal assessment of tolerability in the context of evolving cancer treatment paradigms (EVOLV)
分析 ECOG-ACRIN 不良事件数据,以优化在不断发展的癌症治疗范式 (EVOLV) 背景下纵向耐受性评估的策略
  • 批准号:
    10884567
  • 财政年份:
    2023
  • 资助金额:
    $ 27.66万
  • 项目类别:
AE2Vec: Medical concept embedding and time-series analysis for automated adverse event detection
AE2Vec:用于自动不良事件检测的医学概念嵌入和时间序列分析
  • 批准号:
    10751964
  • 财政年份:
    2023
  • 资助金额:
    $ 27.66万
  • 项目类别:
Understanding the real-world adverse event risks of novel biosimilar drugs
了解新型生物仿制药的现实不良事件风险
  • 批准号:
    486321
  • 财政年份:
    2022
  • 资助金额:
    $ 27.66万
  • 项目类别:
    Studentship Programs
Pediatric Adverse Event Risk Reduction for High Risk Medications in Children and Adolescents: Improving Pediatric Patient Safety in Dental Practices
降低儿童和青少年高风险药物的儿科不良事件风险:提高牙科诊所中儿科患者的安全
  • 批准号:
    10676786
  • 财政年份:
    2022
  • 资助金额:
    $ 27.66万
  • 项目类别:
Pediatric Adverse Event Risk Reduction for High Risk Medications in Children and Adolescents: Improving Pediatric Patient Safety in Dental Practices
降低儿童和青少年高风险药物的儿科不良事件风险:提高牙科诊所中儿科患者的安全
  • 批准号:
    10440970
  • 财政年份:
    2022
  • 资助金额:
    $ 27.66万
  • 项目类别:
Improving Adverse Event Reporting on Cooperative Oncology Group Trials
改进肿瘤学合作组试验的不良事件报告
  • 批准号:
    10642998
  • 财政年份:
    2022
  • 资助金额:
    $ 27.66万
  • 项目类别:
Planar culture of gastrointestinal stem cells for screening pharmaceuticals for adverse event risk
胃肠道干细胞平面培养用于筛选药物不良事件风险
  • 批准号:
    10482465
  • 财政年份:
    2022
  • 资助金额:
    $ 27.66万
  • 项目类别:
Expanding and Scaling Two-way Texting to Reduce Unnecessary Follow-Up and Improve Adverse Event Identification Among Voluntary Medical Male Circumcision Clients in the Republic of South Africa
扩大和扩大双向短信,以减少南非共和国自愿医疗男性包皮环切术客户中不必要的后续行动并改善不良事件识别
  • 批准号:
    10191053
  • 财政年份:
    2020
  • 资助金额:
    $ 27.66万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了