PML antiviral for AIDS

PML 抗艾滋病病毒药物

• 批准号: 7842285
• 负责人: Milton H. Werner
• 金额: $ 26.58万
• 依托单位: INHIBIKASE THERAPEUTICS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7842285
• 关键词: Acquired Immunodeficiency Syndrome; Affect; Animal Model; Animals; Anti-Infective Agents; Antiviral Agents; Benchmarking; Bioavailable; Biological Assay; Biological Products; Cell Culture System; Cell Culture Techniques; Cell membrane; Cells; Cessation of life; Chronic; Cidofovir; Clinic; Clinical; Clinical Research; Clinical Trials; Communicable Diseases; Communities; Country; Development; Disease; Drug Evaluation; Drug Kinetics; Ensure; Evaluation; Family; Funding; Health; Herpesviridae; Human; Immunity; Immunocompromised Host; Immunosuppression; In Vitro; Individual; Infection; Infectious Agent; Infectious Ectromelia; Inflammatory; Influenza A Virus, H5N1 Subtype; JC Virus; Lead; Life; Life Cycle Stages; Maintenance Therapy; Marketing; Measures; Modeling; Mus; Neuraxis; Orphan Drugs; Pathway interactions; Patients; Permeability; Pharmaceutical Preparations; Phase; Polyomavirus; Progressive Multifocal Leukoencephalopathy; Psoriasis; Raptiva; Risk; Rodent Model; Safety; Series; Small Business Innovation Research Grant; Solubility; Staging; Technology; Testing; Therapeutic; Toxic effect; Translating; Transplantation; Tubulin; Tysabri; Urogenital Diseases; Variant; Viral; Viral Physiology; Virus Diseases; aqueous; base; comparative effectiveness; flu; in vivo; indexing; infectious disease treatment; novel; novel strategies; novel therapeutics; pathogen; patient population; pill; public health relevance; research clinical testing; response; small molecule; treatment strategy

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.

描述（由申请人提供）：Inhibikase Therapeutics 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性疾病的新策略。该公司致力于开发一种抗感染产品，用于治疗 JC 病毒感染，这种感染会导致进行性多灶性白质脑病 (PML)，这是一种艾滋病定义的疾病。 PML 是上述患者体内 JC 病毒重新激活的结果，可诱发中枢神经系统炎症性疾病，已证明该疾病的致死率 > 70% 以上。由于这种疾病发生在多种患者身上，Tysabri（治疗多发性硬化症）和 Raptiva（治疗银屑病）等标杆药物因该疾病的零星发生而被迫退出市场，而 Inhibikase 有机会帮助大量患者现在面临 PML 风险的人群。虽然拟开发的产品可以帮助艾滋病患者群体以外的人，但艾滋病患者中发生的 PML 代表了开发治疗 PML 的产品的最佳患者群体。艾滋病患者是活跃的，并且他们基本上以统一的方式接受治疗，因此，这些患者的反应率可能较少受到健康状况、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，可导致泌尿生殖道和中枢神经系统衰弱或致命的疾病。每年受多瘤病毒疾病影响的患者总数远远超过 150,000 名患者，因此，该公司开发抗 JC 抗病毒药物可能会带来额外的好处，为许多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，其中一些可以重新利用，并且已被证明对人类使用是安全的，能够干扰细胞培养物和小鼠中的小鼠多瘤病毒感染。这些小分子代表了与当前传染病治疗范例的巨大背离，因为这些分子针对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同时应用于单个患者的多种传染病。在本案例中，该公司筛选了针对结核病、流感（H5N1）、痘病毒、小鼠多瘤病毒和疱疹病毒的化合物组合，并观察到了体外抗病毒活性。小鼠多瘤病毒与 JC 属于同一多瘤病毒家族，表明该公司的先导化合物可能对 JC 病毒具有活性。该公司拟评估其化合物组合在培养物中对抗 JC 病毒的抗病毒功效，并确定其化合物组合作为可进入临床的药物的效用。不存在用于评价抗JC化合物体内功效的动物模型。因此，在提交初始新药申请以在临床环境中试验有效对抗 PML 的化合物之前，将进一步评估在培养物中具有抗 JC 功效的化合物的安全性和可药性。 公共健康相关性：Inhibikase Therapeutics 是一家早期生物制药公司，正在开发一种新策略来治疗艾滋病患者中发生的致命传染病——进行性多灶性白质脑病。该公司的产品将治疗这种病毒感染，挽救多达 150,000 条生命，并保护超过 500,000 名患者免受这种致命疾病的威胁。