Intranasal Delivery of Peptide Drugs to the Brain

肽药物鼻内递送至大脑

基本信息

批准号：
9455500
负责人：
NAZNEEN N DEWJI
金额：
$ 10万
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：
2012-08-01 至 2017-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9455500
关键词：
Abeta synthesis Affect Alzheimer&apos s Disease Alzheimer&apos s disease model Amino Acids Amyloid beta-Protein Amyloid beta-Protein Precursor Brain Canis familiaris Cell Culture Techniques Cell physiology Clinical Pharmacology Data Development Disease Drug Kinetics Elderly Enzymes Evaluation Formulation Goals Human In Vitro Intranasal Administration Intravenous Manuscripts Modification Mus N-terminal Neurodegenerative Disorders Pathologic Peptides Pharmaceutical Preparations Pharmacotherapy Phase Plasma Population Preparation Small Business Innovation Research Grant Therapeutic Transgenic Mice Water abeta accumulation clinical development drug candidate gamma secretase in vivo interest intravenous administration nervous system disorder neurotoxic new technology novel strategies novel therapeutic intervention peptide drug pre-clinical preclinical development preclinical study presenilin presenilin-1 public health relevance secretase

项目摘要

DESCRIPTION (provided by applicant): Alzheimer's disease (AD) is a progressive and fatal neurological disorder that affects approximately one-tenth of the population over the age of 65. There is currently no cure for the disease. The pathological hallmarks of the disease include the formation and accumulation in the brain of ß-amyloid (Aß), widely recognized to be the major neurotoxic agent in AD. Earlier therapeutic attempts at lowering total Aß production were unsatisfactory as they directly targeted the catalytic activities of ß- or γ-secretase, enzymes known to hydrolyze other substrates as well as APP, many with critical cellular functions. New therapeutic approaches that can inhibit total Aß production without targeting the activities of th ß- or the γ-secretase are therefore of great interest. We have a novel technology that does not target the secretases, which has yielded a potential peptide drug candidate, P8, with the ability to inhibit the production of Aß in vitro and in a Tg mouse model of AD, which is stable and which can be delivered to the brain. We are now developing P8 as a new peptide drug for the treatment of AD. Importantly, Cenna's peptide-induced reductions of total Aß and Aß40 and 42, do not modify or inhibit either ß- or γ-secretase activities. Studies carried out in the Phase SBIR project showed that P8 can be delivered to the brain both, by intranasal and intravenous administration. In this Phase 2 application we propose to carry out studies for the pre-clinical development of P8. Studies will include the characterization of P8, the development of a pre-formulation to support intranasal delivery of P8 in pre-clinical studies, the pharmacokinetic ADME evaluation of P8 and the development of pre-clinical pharmacology/efficacy of P8.

描述（由申请人提供）：阿尔茨海默氏病（AD）是一个计划的神经疾病，大约在65岁以上的人群中。该疾病的病理标志包括在β-淀粉样蛋白的大脑中形成和积累公认是AD的主要神经毒性剂。 ß-或γ-分泌酶非常感兴趣。 AD模型现在正在开发P8作为AD治疗的新肽药物。为了进行P8的临床前开发研究。 P8的临床药理学/功效。