PML antiviral for AIDS

描述(由申请人提供)：Inhibikase Treeutics是一家早期生物制药公司，正在开发一种治疗艾滋病患者感染疾病的新策略。该公司寻求创建一种用于治疗JC病毒感染的抗感染产品，JC病毒感染会导致进行性多灶性白质脑病(PML)，这是一种定义艾滋病的疾病。PML是由上述患者的JC病毒重新激活引起的，在中枢神经系统引起一种已被证明具有70%致命性的炎症性疾病。由于这种疾病发生在各种各样的患者中，由于疾病的零星发生，已迫使Tysabri(用于多发性硬化症)和Raptiva(用于牛皮癣)等基准药物退出市场，Inhibikase有机会帮助目前面临PML风险的非常大的患者群体。虽然拟开发的产品可以帮助艾滋病患者以外的人，但艾滋病患者中出现PML代表了为其开发治疗PML产品的最佳患者群体。艾滋病患者是积极分子，他们在很大程度上得到统一的治疗，因此，这些患者的应答率可能较少受到健康、免疫状态等变化的影响。PML的病原体，多瘤病毒JC，是一小类人类病原体之一，可导致生殖道和中枢神经系统的衰弱或致命疾病。每年受多瘤病毒疾病影响的患者总数远远超过15万人，因此，该公司开发抗JC抗病毒药物可能会带来额外的好处，为一些致命疾病提供新的治疗范例。该公司已经确定了一个小分子家族，其中几个可以被重新利用，并已被证明对人类安全使用，能够在细胞培养和小鼠体内干扰小鼠多瘤病毒的感染。这些小分子与目前的传染病治疗模式大相径庭，因为这些分子针对的是细菌和病毒病原体所依赖的宿主途径，该公司的治疗策略有可能在一个患者身上同时应用于多种传染病。在目前的情况下，该公司已经筛选了其针对结核病、流感(H5N1)、痘、小鼠多瘤和疱疹病毒的化合物组合，并在体外观察到了抗病毒活性。小鼠多瘤属于JC所属的同一多瘤病毒家族，这表明该公司的先导化合物可能对JC病毒具有活性。该公司建议评估其化合物组合在培养中对JC病毒的抗病毒效果，并确定其化合物组合作为可进入临床的药物的效用。目前还没有动物模型来评估抗JC化合物的体内疗效。因此，在提交最初的新药申请以在临床环境中试验抗PML的有效化合物之前，将进一步评估在培养中具有抗JC疗效的化合物的安全性和可药性。 公共卫生相关性：Inhibikase Treeutics是一家早期生物制药公司，正在开发一种新的策略来治疗一种致命的传染病，即进行性多灶性白质脑病，这种疾病发生在艾滋病患者身上。该公司的产品将治疗这种病毒感染，挽救多达15万人的生命，并保护50多万名患者免受这种致命疾病的威胁。

DESCRIPTION (provided by applicant): Inhibikase Therapeutics is an early stage biopharmaceutical company developing a novel strategy for treating infectious disease that occurs in AIDS patients. The Company seeks to create an anti-infective product for treatment of JC viral infection, which leads to progressive multifocal leukoencephalopathy (PML), an AIDS- defining disease. PML results from JC virus reactivation in the aforementioned patients, inducing an inflammatory disease in the central nervous system that has proven to be >70% fatal. Because the disorder occurs in a wide variety of patients, has forced such benchmark drugs as Tysabri (for MS) and Raptiva (for psoriasis) off the market due to the sporadic occurrence of the disease, Inhibikase has the opportunity to help a very large patient population now at risk for PML. While the proposed product to be developed could help people outside of the AIDS patient population, the occurrence of PML in AIDS patients represents the best patient population for which to develop a product to treat PML. AIDS patients are activist and they are largely treated in a uniform fashion, therefore, the response rate in these patients is likely to be less affected by variations in health, in immunity status, etc. The causative agent for PML, the polyomavirus JC, is one of a small family of human pathogens that can lead to debilitating or fatal diseases of the genitourinary tract and the central nervous system. The total patient population affected by polyomaviral diseases is well in excess of 150,000 patients annually, thus, the Company's development of an anti-JC antiviral could have the added benefit of providing a new therapeutic paradigm for a number of fatal diseases. The Company has identified a family of small molecules, several which could be re-purposed and have been shown to be safe-for-human use, that are capable of interfering with mouse polyoma virus infection in cell culture and in the mouse. These small molecules represent a dramatic departure from current treatment paradigms for infectious disease, because these molecules target host pathways upon which bacterial and viral pathogens depend, the Company's treatment strategy has the potential to be applied to multiple infectious diseases simultaneously in a single patient. In the present case, the Company has screened its compound portfolio against TB, flu (H5N1), pox, mouse polyoma and herpes viruses and seen in vitro antiviral activity. Mouse polyoma is of the same family of polyomaviruses that JC belongs to, suggesting that the Company's lead compounds could be active against JC virus. The Company proposes to assess the antiviral efficacy of its compound portfolio against JC virus in culture and to establish the utility of its compound portfolio as drugs that could enter the clinic. No animal models exist for the evaluation of anti-JC compound efficacy in vivo. Thus, compounds with anti-JC efficacy in culture will be further evaluated for safety and drugability prior to filing Initial New Drug applications to trial the effective compounds against PML in the clinical setting. PUBLIC HEALTH RELEVANCE: Inhibikase Therapeutics is an early stage biopharmaceutical company developing a novel strategy for treating a fatal infectious disease, progressive multifocal leukoencephalopathy, that occurs in AIDS patients. The Company's products will treat this viral infection and save up to 150,000 lives and protect more than 500,000 patients from becoming at risk for this fatal disorder.