Administrative Supplement to restore fee funds

项目摘要 创伤性脑损伤（TBI）导致有害的行为功能障碍和脑损伤。 神经变性，但不幸的是，目前没有有效的药物TBI 治疗基础的第一阶段STTR赠款是开发一类新的TBI药物， 组织蛋白酶B。基因缺失小鼠组织蛋白酶B基因会导致 控制性皮质撞击（CCI）TBI的行为和病理学显著改善 相对于表达该蛋白酶的动物的模型。此外，施用工具化合物， 抑制组织蛋白酶B，称为E64 d和E64 c，对CCI后的野生型小鼠也产生 类似的改进。组织蛋白酶B基因敲除小鼠是健康的，并且在儿科中进行了先前的研究。 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 化合物对于治疗TBI可能是有效和安全的。基础补助金将决定 CCI小鼠模型中工具化合物的药理学参数和功效 受赠方美国生命科学制药公司开发了 工具化合物和获得的专利保护这些衍生物在美国和 欧洲这些氘衍生物随后将被开发为TBI治疗剂。 立即申请行政补充，以恢复被削减的资金， 由于在授予时资金不足，基本赠款的费用类别 进行了费用类别允许不受限制地使用资金。补充奖将是 用于支付美国和欧洲的持续专利费用。这笔支出是 绝对必要，因为没有这些专利，TBI疗法就不能被用于治疗创伤性脑损伤。 商业开发。

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.