LAUR-201 (V-Smart®-TNV for Neuro-HIV): Novel V-Smart® Nanomedicine for Treatment of HAND

LAUR-201（V-Smart®-TNV for Neuro-HIV）：用于治疗手部手足病的新型 V-Smart® 纳米药物

• 批准号: 10544378
• 负责人: ELIAHU HELDMAN
• 金额: $ 60万
• 依托单位: LAUREN SCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-20 至 2024-08-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10544378
• 关键词: Address; Advanced Development; Affect; Animal Model; Anti-HIV Agents; Anti-Retroviral Agents; Biotechnology; Blood; Blood - brain barrier anatomy; Brain; Cells; Chemical Structure; Clinical; Cognitive deficits; Collaborations; Combined Modality Therapy; Data; Development; Diagnosis; Disease; Disease model; Doctor of Medicine; Doctor of Philosophy; Dose; Drug Kinetics; Encapsulated; FDA approved; Functional disorder; Goals; HIV; HIV therapy; HIV-1; HIV-associated neurocognitive disorder; Health; Highly Active Antiretroviral Therapy; Human; Immunology; Impaired cognition; In Vitro; Individual; Intravenous; Israel; Medical; Memory impairment; Microbiology; Microglia; Modeling; Mus; Neuraxis; Neurocognitive; Neurology; New York; Oral Administration; Outcome; Pathogenesis; Pathologic; Pathology; Patients; Penetration; Peripheral; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Prevention; Primates; Problem Solving; Regimen; Research; SIV; Safety; Science; Small Business Innovation Research Grant; Study models; Symptoms; Technology; Tenofovir; Testing; Therapeutic; Therapeutic Agents; Toxic effect; Viral; Virus Replication; Work; antiretroviral therapy; base; blood-brain barrier penetration; commercial application; design; efficacy clinical trial; efficacy study; efficacy testing; innovation; macrophage; medical schools; mouse model; nanomedicine; neuroAIDS; neurocognitive disorder; nonhuman primate; novel; object recognition; pill; prevent; standard care; truvada; Address; Advanced Development; Affect; Animal Model; Anti-HIV Agents; Anti-Retroviral Agents; Biotechnology; Blood; Blood - brain barrier anatomy; Brain; Cells; Chemical Structure; Clinical; Cognitive deficits; Collaborations; Combined Modality Therapy; Data; Development; Diagnosis; Disease; Disease model; Doctor of Medicine; Doctor of Philosophy; Dose; Drug Kinetics; Encapsulated; FDA approved; Functional disorder; Goals; HIV; HIV therapy; HIV-1; HIV-associated neurocognitive disorder; Health; Highly Active Antiretroviral Therapy; Human; Immunology; Impaired cognition; In Vitro; Individual; Intravenous; Israel; Medical; Memory impairment; Microbiology; Microglia; Modeling; Mus; Neuraxis; Neurocognitive; Neurology; New York; Oral Administration; Outcome; Pathogenesis; Pathologic; Pathology; Patients; Penetration; Peripheral; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Prevention; Primates; Problem Solving; Regimen; Research; SIV; Safety; Science; Small Business Innovation Research Grant; Study models; Symptoms; Technology; Tenofovir; Testing; Therapeutic; Therapeutic Agents; Toxic effect; Viral; Virus Replication; Work; antiretroviral therapy; base; blood-brain barrier penetration; commercial application; design; efficacy clinical trial; efficacy study; efficacy testing; innovation; macrophage; medical schools; mouse model; nanomedicine; neuroAIDS; neurocognitive disorder; nonhuman primate; novel; object recognition; pill; prevent; standard care; truvada

Lauren Sciences goal is to advance development of its innovative V-Smart® Nanomedicine for Neuro-HIV, LAUR- 201 (V-Smart®-Tenofovir for Neuro-HIV), as a disease-modifying therapeutic for the critical unmet medical needs of 50% of the 40 million HIV patients worldwide who, despite suppressive antiretroviral therapy (ART), suffer from HIV-associated neurocognitive disorders (HAND). Currently, there are no FDA-approved therapies for HAND, and clinical symptoms include quantifiable cognitive deficits hallmarked by impaired memory. A major shortcoming of first-line HIV therapies is lack of sustained potent delivery to the central nervous system (CNS), which LAUR-201 is designed to solve. Tenofovir (TNV), a component of first-line combination antiretroviral (ARV) pills Truvada and Atripla, is widely used and effective in HIV-infected individuals; however, TNV hardly crosses the blood brain barrier (BBB). Since TNV has the poorest BBB penetration of typical ARV drugs, and is contained in the most widely prescribed first-line therapy regimens, delivering TNV into the CNS may be the most useful to eliminate HIV in the CNS. TNV is particularly effective in penetrating and eliminating HIV from the predominant cells harboring HIV in the brain, and ongoing low-level viral replication in the brain confers a unique sanctuary for HIV, which further contributes to HAND pathogenesis and the CNS HIV reservoir. Lauren Sciences used its novel cutting edge V-Smart® Platform to develop LAUR-201, proven in preliminary data to: (1) encapsulate high TNV concentrations, (2) retain TNV chemical structure, (3) deliver therapeutic TNV concentrations into mouse brain after systemic administration, without apparent toxicity, and (4) reach TNV brain levels in mice well above those attained in ART-treated patients’ blood. This SBIR Phase I is critical to prove feasibility of LAUR-201 to: (1) maintain TNV efficacy in vitro and therapeutic levels in mice brain, and (2) be effective in the murine HAND model, i.e., suppress persistent HIV in the CNS and ameliorate cognitive deficits conferred by HIV, without toxicity, compared to free TNV, after systemic administration. LAUR-201 is a breakthrough solution for HAND, solves the TNV brain delivery issue, targets persistent HIV within the CNS and can impact, and exert a sustained, powerful influence on, this high unmet medical need. LAUR-201 is intended to become the first FDA-approved drug to safely prevent HAND and overcome Neuro-HIV as part of the standard treatment for HIV patients.

Lauren Sciences的目标是推进其创新的V-SMART®纳米医学，用于神经hiv，Laur- 5 在全球4000万名艾滋病毒患者中，有50％，dospite抑制抗逆转录病毒疗法（ART），患者 来自与HIV相关的神经认知障碍（手）。目前，没有FDA批准的疗法 手和临床符号包括可量化的认知缺陷，以记忆受损为标志。专业 一线HIV疗法的缺点是缺乏向中枢神经系统（CNS）的持续有效递送 Laur-2012旨在解决。 Tenofovir（TNV），一线组合抗逆转录病毒（ARV）的组成部分 Truvada和Atripla药丸在感染HIV的个体中被广泛使用且有效。但是，TNV几乎没有交叉 血脑屏障（BBB）。由于TNV具有典型ARV药物的BBB渗透最差，并且包含 在最广泛的一线治疗方案中，将TNV输送到中枢神经系统中可能是最有用的 消除中枢神经系统中的艾滋病毒。 TNV在渗透和消除HIV中特别有效 大脑中携带艾滋病毒的细胞，大脑中持续的低级病毒复制赋予了独特的庇护 对于HIV，这进一步有助于手动发病机理和中枢神经系统HIV储藏。劳伦科学使用了 开发LAUR-201的新型Cutting Edge V-Smart®平台，在初步数据中证明：（1）封装高 TNV浓度，（2）保留TNV化学结构，（3）将热TNV浓度输送到小鼠中 全身给药后的大脑，没有明显的毒性，（4）到达高于小鼠的小鼠TNV大脑水平 那些附属于艺术治疗的患者的血液中的人。 SBIR I期对于证明Laur-201的可行性至关重要： （1）在小鼠大脑中维持体外和热水平的TNV有效性，（2）在鼠手中有效 模型，即抑制中枢神经系统中的持续艾滋病毒，并改善艾滋病毒赋予的认知防御 与自由TNV相比，全身给药后的毒性。 LAUR-2010是一个突破性解决方案， 解决TNV脑输送问题，针对中枢神经系统内的持续艾滋病毒，并可能影响并执行持续的， 对这种高未满足的医疗需求的强大影响。 LAUR-2012旨在成为第一个FDA批准的 作为艾滋病毒患者标准治疗的一部分，药物可以安全防止手并克服神经HIV。