Progressing the Pre-clinical development of P8 for Alzheimer's Disease

阿尔茨海默病P8的临床前研究进展 这项SBIR竞争性IIB期续展申请将继续进行临床前开发 Cenna的主要候选多肽药物P8用于治疗阿尔茨海默病(AD)。目前还没有治愈的方法 这种疾病。这种疾病的病理特征包括脑组织中血管生成和积聚。 被广泛认为是阿尔茨海默病的主要神经毒剂。较早的治疗尝试降低总 A？生产不令人满意，因为它们直接针对？或γ-分泌酶的催化活性， 已知的水解酶除了APP外还有其他底物，许多都具有关键的细胞功能。新的 一种治疗方法，可以抑制总的A？产生，而不针对？？或γ的活动？ 因此，分泌酶引起了极大的兴趣。我们有一种不针对秘密的新技术， 它已经产生了一种潜在的多肽候选药物P8，能够抑制A？in的产生 在AD的体外和转基因小鼠模型中。P8正在被开发为一种治疗该疾病的新的多肽药物 公元一代的。在这项申请中，我们建议在过去两年取得实质性进展的基础上再接再厉 第二阶段资金，并继续进行P8的临床前开发。具体来说，我们建议进一步 开发P8皮下注射用药配方，开展非GLP研究 将对配方中的P8进行毒理学和毒代动力学评估的研究，以促进 它进入了GLP监管毒理学测试，提供了安全概况的全面评估。 P8制剂的疗效将在APP转基因小鼠身上进行评估。较大数量的非GLP、GLP 还将为当前拟议的工作和未来的工作合成和表征P8的GMP等级 支持IND的毒理学和第一阶段研究。

Progressing the Preclinical Development of P8 for Alzheimer's disease This SBIR competitive Phase IIB renewal application is to continue with the preclinical development of Cenna's lead peptide drug candidate, P8, to treat Alzheimer's disease (AD). There is currently no cure for the disease. 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. 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 besides APP, many with critical cellular functions. New therapeutic approaches that can inhibit total Aß production without targeting the activities of the 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 transgenic mouse model of AD. P8 is being developed as a new peptide drug for the treatment of AD. In this application we propose to build upon the substantial progress made in the last two years of Phase II funding and to continue with the preclinical development of P8. Specifically, we propose to further develop the formulation of P8 as a subcutaneous injectable drug and carry out investigative non-GLP studies that will provide a toxicological and toxicokinetic assessment of P8 in formulation in order to facilitate its movement into GLP regulatory toxicological testing, which provides a full assessment of the safety profile. Efficacy of P8 in formulation will be assessed in APP transgenic mice. Larger quantities of non-GLP, GLP and GMP grades of P8 will also be synthesized and characterized for the current proposed work and future IND-enabling toxicology and Phase 1 studies.