Development of the Novel Antifungal VT-1129 for Cryptococcal Meningitis

开发治疗隐球菌性脑膜炎的新型抗真菌药物 VT-1129

• 批准号: 9205571
• 负责人: Elizabeth Ottinger
• 金额: $ 41.72万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9205571
• 关键词: Development; Novel; Antifungal; VT; 1129

Cryptococcal meningitis (CM) results from infection by the encapsulated yeasts Cryptococcus neoformans and Cryptococcus gattii and is observed almost exclusively in immune-compromised individuals. The enormous population of HIV-infected people in sub-Saharan Africa (estimated to be more than 20 million), with inadequate access to antiretroviral therapy, is highly susceptible to this disease. The most common drug treatment for CM in this patient population is high-dose fluconazole monotherapy, but it achieves only a 40 percent survival rate after 10 weeks of treatment. A more potent anti-fungal drug that can be given orally once a day would likely provide a significant improvement in survival for this neglected population. This project includes pre-clinical Investigational New Drug (IND)-enabling studies that will evaluate VT-1129 as a novel, oral, stand-alone drug candidate for the treatment of CM. TRND researchers conducted validation studies for the lead compound, VT-1129, including pharmacokinetic, efficacy and toxicology studies in rodents and non-rodents, enabling selection of an optimal dosing regimen to balance efficacy and safety. The TRND team optimized a synthetic process for scaled-up production of drug at a low cost that will support treatment of patients in the developing world. Additional collaborative studies were completed with the Centers for Disease Control and Prevention (CDC) to test the in vitro efficacy of the molecule against 400 fungal strains from Africa. This TRND support enabled Viamet to successfully raise venture capital funding to continue development of the de-risked candidate.

隐球菌性脑膜炎（CM）是由被包膜的酵母菌新型隐球菌和加蒂隐球菌感染引起的，几乎只在免疫功能低下的个体中观察到。撒哈拉以南非洲感染艾滋病毒的人口众多（估计超过2 000万），无法充分获得抗逆转录病毒治疗，极易感染这种疾病。在这一患者群体中，CM最常用的药物治疗是大剂量氟康唑单药治疗，但治疗10周后生存率仅为40%。一种更有效的抗真菌药物，可以每天口服一次，可能会显著改善这一被忽视人群的生存。该项目包括临床前新药研究（IND），将评估VT-1129作为治疗CM的新型口服独立候选药物。

项目成果

Isoproternenol increases vascular volume expansion and urinary output after a large crystalloid bolus in healthy volunteers.

• DOI: 10.1097/shk.0000000000000233
• 发表时间: 2014-11
• 期刊: Shock (Augusta, Ga.)
• 作者: Asmussen S;Salter M;Prough DS;Kramer GC;Svensen C;Sheffield-Moore M;Kinsky MP
• 通讯作者: Kinsky MP