重新利用双羟萘酸吡维铵治疗家族性腺瘤性息肉病 (FAP)-猫眼课题宝

重新利用双羟萘酸吡维铵治疗家族性腺瘤性息肉病 (FAP)

批准号：

9930731

负责人：

Darren Orton

金额：

$137.6万

依托单位：

STEMSYNERGY THERAPEUTICS, INC.

依托单位国家：

美国

项目类别：

财政年份：

2018

资助国家：

美国

项目状态：

已结题

起止时间：

2018-03-15 至 2021-08-31

来源：

https://reporter.nih.gov/project-details/9930731

关键词：

Adenomatous Polyposis Coli Age Animal Model Animals Anthelmintics Award Back Canis familiaris Cardiovascular system Cause of Death Chemistry Chemoprevention Clinic Clinical Clinical Research Colectomy Colon Colorectal Cancer DNA Sequence Alteration Data Defecation Development Discrimination Disease Documentation Dose Drug Kinetics Enterobiasis Excision Exhibits Exposure to FDA approved Feces Flatulence Frequencies Future Goals Guidelines Hereditary Disease In Vitro Incontinence Individual International Intestinal Neoplasms Intestines Investigational Drugs Investigational New Drug Application Legal patent Literature Malignant Neoplasms Medical Methods Mutation Neuraxis Non-Rodent Model Oral Orphan Drugs Patients Pharmaceutical Preparations Pharmacology Pharmacotherapy Phase Phase I Clinical Trials Polyps Precancerous Polyp Prevalence Process Protocols documentation Pyrvinium pamoate Quality of life Rare Diseases Recommendation Regulatory Affairs Regulatory Pathway Respiratory System Rodent Safety Small Business Innovation Research Grant Teenagers Toxic effect Validation WNT Signaling Pathway acute toxicity base bench to bedside cancer cell drug synthesis effective therapy financial incentive inhibitor/antagonist meetings mouse model multidisciplinary new therapeutic target off-patent pre-clinical prevent programs research clinical testing scale up side effect stability testing standard of care symposium targeted treatment

项目摘要

项目成果

Darren Orton的其他基金

相似基金

相关文献

中文摘要

翻译

摘要患有罕见的遗传性疾病家族性腺瘤性息肉病（FAP）的个体会发展成数千种早期的癌前息肉并最终发展为结直肠癌（CRC）。现行标准治疗FAP的方法是结肠切除术。然而，结肠切除术不可避免的副作用是衰弱。此外，委员会认为，结肠切除术并不能防止结肠外肠道肿瘤的发生，而肿瘤是导致死亡的主要原因结肠切除术后目前FDA还没有批准用于治疗或化学预防FAP的药物患者我们已经证明，pyrvinium可以重新用作WNT信号传导的有效抑制剂，在FAP的动物模型中是有效的。口服给药双羟萘酸吡维铵产生可忽略的全身性它可以减少接触并限制对肠道的接触，从而降低毒性的可能性。将这些数据提交给 FDA授予我们孤儿药称号，专门为FAP患者销售pyrvinium。澄清将吡维铵作为FAP患者的再用途药物带回临床所需的步骤， 505（B）（2）监管机制，我们最近与FDA进行了IND前会议。第一阶段/第二阶段快速通道申请是由FDA对成功的研究性新药（IND）申请的建议驱动的在FAP的治疗中，如果成功的话，将吡维铵用于FAP患者，代表1）治疗和生活质量的重大改善，以及2）成功的床旁治疗应用合理选择的靶向治疗。

英文摘要

ABSTRACT Individuals with the rare, inherited disorder Familial Adenomatous Polyposis (FAP) develop thousands of precancerous polyps at an early age and ultimately develop colorectal cancer (CRC). The current standard of care for FAP is colectomy. However, unavoidable side-effects of colectomy are debilitating. Furthermore, colectomy does not prevent subsequent development of extra-colonic intestinal tumors, the main cause of death post-colectomy. There are currently no drugs FDA approved for the treatment or chemoprevention of FAP patients. We have demonstrated that pyrvinium can be repurposed as a potent inhibitor of WNT signaling and is efficacious in an animal model of FAP. Oral dosing of pyrvinium pamoate produces negligible systemic exposure and limits the exposure to the gut which reduces the likelihood of toxicity. Submitting these data to the FDA, we were awarded an Orphan Drug Designation to market pyrvinium exclusively for FAP patients. To clarify the steps required to take pyrvinium back into the clinic as a repurposed agent for FAP patients, using a 505(b)(2) regulatory mechanism, we recently had a pre-IND meeting with the FDA. This Phase I/II Fast-Track application is driven by the FDA’s recommendations for a successful Investigational New Drug (IND) application for pyrvinium in the treatment of FAP. The repurposing of pyrvinium for FAP patients, if successful, would represent 1) A major improvement in therapy and in the quality of life, and 2) The successful bench to bedside application of a rationally selected targeted therapy.

期刊论文(0)

专著(0)

科研奖励(0)

会议论文