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.

劳伦科学的目标是推进其创新的V-Smart®纳米医学的发展，用于神经艾滋病毒，LAUR- 201（V-Smart®-Tenofovir for Neuro-HIV），作为一种疾病缓解治疗剂，用于满足关键的未满足的医疗需求 全世界4000万艾滋病患者中有50%尽管接受了抑制性抗逆转录病毒治疗（ART）， HIV相关的神经认知障碍（HAND）。目前，没有FDA批准的治疗方法用于 临床症状包括以记忆受损为特征的可量化的认知缺陷。一个主要 一线HIV治疗的缺点是缺乏持续有效的递送至中枢神经系统（CNS）， 而LAUR-201正是为了解决这个问题而设计的。替诺福韦（TNV），一线联合抗逆转录病毒（ARV）的一个组成部分 药丸Truvada和Atripla，被广泛使用，对HIV感染者有效;然而，TNV几乎不交叉 血脑屏障（BBB）。由于TNV在典型的ARV药物中具有最差的BBB渗透性， 在最广泛的一线治疗方案中，将TNV递送到CNS中可能是最有用的， 消除中枢神经系统中的艾滋病毒。TNV在穿透和消除艾滋病毒方面特别有效， 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提供了一个独特的避难所 对于HIV，这进一步促进了HAND发病机制和CNS HIV储库。劳伦科学公司利用其 用于开发LAUR-201的新型尖端V-Smart®平台，初步数据证明：（1）封装高 TNV浓度，（2）保留TNV化学结构，（3）将治疗TNV浓度输送到小鼠体内 在全身给药后，TNV在小鼠脑中的水平远高于 在接受ART治疗的患者血液中获得的那些。该SBIR第I阶段对于证明LAUR-201的可行性至关重要，以： (1)维持体外TNV功效和小鼠脑中的治疗水平，和（2）在鼠HAND中有效 模型，即，抑制CNS中持续存在的HIV，改善HIV引起的认知缺陷， 毒性，与游离TNV相比，全身给药后。LAUR-201是HAND的突破性解决方案， 解决了TNV脑递送问题，靶向CNS内的持续HIV，并且可以影响和施加持续的， 对这种高度未满足的医疗需求的巨大影响。LAUR-201有望成为首个获得FDA批准的 作为HIV患者标准治疗的一部分，该药可安全预防HAND并克服Neuro-HIV。