Administrative Supplement to restore fee funds

恢复收费资金的行政补充

• 批准号: 9982655
• 负责人: GREGORY R HOOK
• 金额: $ 3.62万
• 依托单位: AMERICAN LIFE SCIENCE PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-25 至 2020-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9982655
• 关键词: Administrative Supplement; American; Animals; Award; Behavioral; Biological Sciences; Brain; Categories; Cathepsins B; Cause of Death; Deuterium; Development; Europe; Expenditure; Fees; Functional disorder; Funding; Genes; Grant; Investments; Knockout Mice; Legal patent; Mission; Modeling; Mus; Nerve Degeneration; Pathology; Peptide Hydrolases; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Small Business Technology Transfer Research; Therapeutic; Time; Traumatic Brain Injury; United States; Wild Type Mouse; controlled cortical impact; cost; disability; inhibitor/antagonist; mouse model; off-patent; pediatric patients; tool

Project Summary Traumatic brain injury (TBI) causes detrimental behavioral dysfunctions and brain neurodegeneration but, unfortunately, there currently is no effective pharmaceutical TBI treatment. The underlying Phase 1 STTR grant is to develop a new class of TBI drugs that inhibit the protease cathepsin B. Genetically deleting the cathepsin B gene in mice results in substantial behavioral and pathology improvements in the controlled cortical impact (CCI) TBI model relative to animals expressing that protease. Moreover, administering tool compounds, which inhibit cathepsin B, called E64d and E64c, to wild-type mice following CCI also produce similar improvements. Cathepsin B knockout mice are healthy and prior studies in pediatric patients found E64d to be safe. Thus, there is reason to believe that cathepsin B inhibitor compounds may be effective and safe for treating TBI. The underlying grant will determine pharmacological parameters and efficacy for the tool compounds in the CCI mouse model The Grantee, American Life Science Pharmaceuticals, developed deuterium derivatives of the tool compounds and obtained patents protecting those derivatives in the United States and Europe. Those deuterium derivatives will be subsequently developed as TBI therapeutics. The instant application is for an Administrative Supplement to restore funds that were cut from the Fee category of the underlying grant due to insufficient funds at the time the award was made. The Fee category allows for unrestricted use of funds. The Supplemental Award will be used to pay for on-going patent costs in the United States and Europe. That expenditure is absolutely essential because without those patents, the TBI therapeutics cannot be commercially developed.

项目摘要 创伤性脑损伤（TBI）引起有害行为功能障碍和大脑 神经变性，但不幸的是，目前没有有效的药物TBI 治疗。基础1阶段的STTR赠款是开发一种抑制的新类TBI药物 蛋白酶组织蛋白酶B.在小鼠中遗传删除组织蛋白酶B基因导致 受控皮质影响（CCI）TBI的大量行为和病理改善 相对于表达该蛋白酶的动物的模型。此外，管理工具化合物， 抑制组织蛋白酶B（称为E64D和E64C）在CCI之后也会产生野生型小鼠 类似的改进。组织蛋白酶B基因敲除小鼠很健康，并且先前在小儿研究 患者发现E64D是安全的。因此，有理由相信组织蛋白酶B抑制剂 化合物对治疗TBI可能是有效且安全的。基础赠款将确定 CCI小鼠模型中工具化合物的药理参数和功效 受赠人，美国生命科学药物，开发了氘衍生物的 工具化合物并获得了保护这些衍生品的专利和 欧洲。这些氘衍生物随后将作为TBI疗法开发。 即时申请是为了恢复从中削减的资金的行政补品 由于资金不足，该裁决是在 制成。费用类别允许不受限制地使用资金。补充奖项将是 用于支付美国和欧洲正在进行的专利费用。那支出是 绝对是必不可少的 商业发展。