IND-Enabling Pre-clinical Development of Modified P8 for the Treatment of Alzheimer's Disease

IND 促进修饰 P8 治疗阿尔茨海默病的临床前开发

基本信息

批准号：
10261539
负责人：
NAZNEEN N DEWJI
金额：
$ 161.04万
依托单位：
CENNA BIOSCIENCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10261539
关键词：
Abeta synthesis Affect Alzheimer&apos s Disease Alzheimer&apos s disease model Amino Acids Amyloid beta-Protein Applications Grants Brain Cell physiology Clinical Research Clinical Trials Development Plans Disease Dose Enzymes Funding Future Grant In Vitro Length Medical Methods Monkeys Neurodegenerative Disorders Pathologic Pharmacology Pharmacotherapy Phase Phase I Clinical Trials Population Preparation Publishing Rattus Readiness Safety Small Business Innovation Research Grant Therapeutic Toxic effect Transgenic Mice Work beta secretase clinical development commercialization drug candidate first-in-human gamma secretase human old age (65+)in vivo inhibitor manufacturing scale-up medication safety meetings neurotoxic new technology novel novel therapeutic intervention peptide drug pre-clinical preclinical development preclinical study product development programs scale up secretase subcutaneous

项目摘要

Modified Project Summary/Abstract Section The focus of this Type 2 Commercialization Readiness Program application is on the regulatory requirements necessary to support regulatory submissions relating to pre-clinical development of Cenna’s peptide drug candidate mP8. mP8, a modified stabilized version of the previously published P8 is being developed as a new, first-in-class peptide drug for the treatment of Alzheimer’s disease (AD). This application builds on the substantial progress made under the previously funded SBIR Phase 2 and 2B grants. There is currently no cure for AD. The pathological hallmarks of the disease include the formation and accumulation in the brain of Aß, widely recognized to be the major neurotoxic agent in AD. All therapeutic attempts targeting Aß production have failed as they directly targeted the catalytic activities of ß- or γ-secretase, enzymes known to hydrolyze other substrates besides APP, many with critical cellular functions. Most clinical trials of both γ- and more recently ß- secretase inhibitors have been discontinued due to safety and other issues. New therapeutic approaches that can inhibit total Aß production without targeting the activities of the ß- or the γ-secretase are therefore urgently needed. We have a novel technology that does not target the secretases, which has yielded several potential peptide drug candidates with the ability to substantially and specifically inhibit the production of Aß in vitro and in vivo. In this renewal application we propose to complete pre-clinical studies on mP8 necessary for an IND submission. Proposed aims are to get scaled-up quantities of GLP and GMP grade mP8 synthesized, to carry out non-GLP dose-range-finding studies of mP8 in monkeys and rats, to develop and validate bioanalytical methods for GLP, to conduct IND-enabling drug safety toxicity studies in rats and monkeys and to investigate IND-enabling GLP safety pharmacology in rats and monkeys. The successful accomplishment of the proposed studies will complete a major part of the requirements towards submission of an IND to the FDA in preparation for Phase 1 clinical trials.

修改的项目摘要/摘要部分这种类型2的通讯准备计划的重点是与Cenna肽药物候选药物MP8的临床前开发有关的抢劫，这是先前发表的P8的修改后的稳定版本，它是一种新的，第一类肽药物为了治疗阿尔茨海默氏病（AD）。 - 分泌酶，除了应用程序以外，已知其他底物的酶具有关键的细胞功能。生产不靶向ß-或泌尿液的活性，我们有一种新型的技术，可以针对分泌的肽药物候选物，能够在这个续签Applete中脱离体外和体内，并不利地说明了dose。对GLP和GMP级MP8的临时研究，合成的MP8，以在猴子和大鼠中对MP8进行非GLP剂量范围研究 - 在大鼠和猴子中增强GLP安全性。