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

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 的目标是推进其针对 Neuro-HIV 的创新 V-Smart® 纳米药物的开发，LAUR- 201（V-Smart®-Tenofovir for Neuro-HIV），作为一种缓解疾病的疗法，用于满足未满足的关键医疗需求 全球 4000 万艾滋病毒患者中，尽管接受了抑制性抗逆转录病毒治疗 (ART)，仍有 50% 的患者仍遭受痛苦 目前，尚无 FDA 批准的治疗方法。 HAND 和临床症状包括以 A 大​​调记忆受损为特征的可量化认知缺陷。 一线艾滋病毒疗法的缺点是缺乏持续有效的中枢神经系统（CNS）传递， LAUR-201 旨在解决这一问题，替诺福韦 (TNV) 是一线联合抗逆转录病毒药物 (ARV) 的组成部分。 Truvada 和 Atripla 药物在 HIV 感染者中广泛使用且有效，但 TNV 很难交叉； 由于 TNV 的 BBB 穿透力是典型 ARV 药物中最差的，因此被抑制。 在最广泛使用的一线治疗方案中，将 TNV 输送到中枢神经系统可能是最有效的治疗方案。 消除中枢神经系统中的艾滋病毒对于渗透和消除主要的艾滋病毒特别有效。 大脑中携带艾滋病毒的细胞，以及大脑中持续的低水平病毒复制，为大脑提供了一个独特的避难所 HIV，这进一步促进了 HAND 发病机制，CNS HIV 储存库使用了它。 用于开发 LAUR-201 的新颖尖端 V-Smart® 平台，初步数据证明能够：(1) 封装高 TNV 浓度，(2) 保留 TNV 化学结构，(3) 将治疗性 TNV 浓度输送到小鼠体内 全身给药后脑部无明显毒性，并且（4）在小鼠体内达到TNV脑部水平远高于 在接受 ART 治疗的患者血液中获得的结果对于证明 LAUR-201 的可行性至关重要： (1) 维持 TNV 的体外功效和小鼠脑中的治疗水平，以及 (2) 在小鼠 HAND 中有效 模型，即抑制中枢神经系统中持续存在的艾滋病毒并改善艾滋病毒造成的认知缺陷，而无需 与游离 TNV 相比，LAUR-201 是 HAND 的突破性解决方案。 解决 TNV 大脑输送问题，针对中枢神经系统内持续存在的 HIV，并可以影响并发挥持续的、 LAUR-201 旨在成为第一个获得 FDA 批准的药物。 作为 HIV 患者标准治疗的一部分，安全预防 HAND 并克服 Neuro-HIV 的药物。